Experimental studies

Change template to: announce

array(3) { [0]=> array(49) { ["IBLOCK_SECTION_ID"]=> string(3) "203" ["~IBLOCK_SECTION_ID"]=> string(3) "203" ["ID"]=> string(4) "2048" ["~ID"]=> string(4) "2048" ["IBLOCK_ID"]=> string(1) "2" ["~IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(252) "Опыт применения радиомически-ориентированной навигационной системы дополненной реальности при биопсии новообразования нижней челюсти" ["~NAME"]=> string(252) "Опыт применения радиомически-ориентированной навигационной системы дополненной реальности при биопсии новообразования нижней челюсти" ["ACTIVE_FROM"]=> NULL ["~ACTIVE_FROM"]=> NULL ["TIMESTAMP_X"]=> string(22) "01/26/2022 12:54:02 pm" ["~TIMESTAMP_X"]=> string(22) "01/26/2022 12:54:02 pm" ["DETAIL_PAGE_URL"]=> string(161) "/en/archive/tom-10-nomer-3-4/eksperimentalnye-issledovaniya/opyt-primeneniya-radiomicheski-orientirovannoy-navigatsionnoy-sistemy-dopolnennoy-realnosti-pri-biop/" ["~DETAIL_PAGE_URL"]=> string(161) "/en/archive/tom-10-nomer-3-4/eksperimentalnye-issledovaniya/opyt-primeneniya-radiomicheski-orientirovannoy-navigatsionnoy-sistemy-dopolnennoy-realnosti-pri-biop/" ["LIST_PAGE_URL"]=> string(12) "/en/archive/" ["~LIST_PAGE_URL"]=> string(12) "/en/archive/" ["DETAIL_TEXT"]=> string(14372) "

Introduction

Medical imaging is one of the main diagnostic methods that defines the treatment strategy. The main advantage of X-ray data examination is its ability for digitilization. The data obtained by the digitization provide multidimensional data which, due to appropriate standardization and analysis, enable additional information about specific features of the diseases [1].

Radiomics is a quantitative method for the analysis of digitized X-ray images, which is based on mathematical analysis [2]. Radiomics allows quantifying texture information by mathematically extracting the spatial distribution of signal intensities and pixel relationships [2, 3]. The concept of radiomics is based on the search for imaging biomarkers that are specific to certain pathological processes undetectable by standard visual inspection of the generated images. Visually noticeable differences in the intensity, shape and texture of the image can be quantified using radiomics, which allows the more objective process of interpreting X-ray images [3]. The key purpose of radiomics applied for medical image analysis is to reveal objective non-invasive prognostic biomarkers of the disease, presuming its further transition to personalized medicine [4].

Four main steps for extraction of radiomic data from medical images are as follows:
1. Acquisition of images using methods of radiological diagnostics;
2. Segmentation of the region of interest (ROI or volume of interest – VOI);
3. Extraction of radiomic features;
4. Obtaining biomarkers of imaging [5].

However, in order to improve the accuracy of diagnostic procedures, such as biopsy of the neoplasm, the obtained data require integration into the clinical picture. This can be done by directly overlaying the region of the location of the imaging biomarker on the region of neoplasm through augmented reality.

Augmented reality is the projection of any digital information (images, video, text, graphics, etc.) over a real image [6]. As a result, the real world is supplemented with artificial elements and new information. This technology is becoming increasingly popular in various fields of medicine, including maxillofacial surgery [6]. The following is required with respect to ensurance of the technology functioning:
1. Acquisition of images using methods of conventional radiology diagnostics (obtaining data on a three-dimensional object);
2. Segmentation of the region of interest (e.g., neoplasms);
3. Loading the region of interest into augmented reality glasses;
4. Conducting surgery in augmented reality, focusing on the location of the region of interest.

As seen from the below algorithms, working in radiomics and augmented reality has several identical stages. Moreover, integration of the latter technique contributes to creation of a radio-oriented navigation system (Fig. 1).

Figure 1. Algorithm for radiome analysis of Cone Beam Computed Tomography images and the algorithm for the operation of augmented reality technology (Original picture)

The purpose hereof is to present an algorithm for radiomic image analysis using the example of a neoplasm of the lower jaw and to demonstrate practical applicability of this technology, i.e., to conduct a radiomically targeted biopsy of a neoplasm directed by the augmented reality technology.

Materials and methods

The authors used a comprehensive open source platform PyRadiomics, built into 3D Slicer, the interface of the software was designed for analyzing and working with medical images, to handle the radiological data. The software is intended for processing and extraction of radiomic characteristics from medical images using a large panel of hard-coded function algorithms (Fig. 2).

Figure 2. Appearance of the software 3D Slicer

Stage 1. Acquisition of images using methods of radiology diagnostics

Figure 3. Appearance of the occlusal splint with X-ray contrast marks (A); Patient positioning at the cone-beam computed tomography with occlusal splint (B)

The first stage is to identify the clinical problem and obtain a digital image, excluding low quality studies. When planning to perform an intervention in augmented reality, it is necessary to perform an X-ray examination using X-ray contrast markers, according to which the augmented reality marker will be localized and calibrated for the prospective surgery.

Taking into account the mobility of lower jaw, an individual occlusal splint with X-ray contrast marks and an integrated holder for the augmented reality marker was pre-fabricated. Cone beam computed tomography (CBCT) was performed with a mouthguard containing X-ray contrast marks fixed in the patient's mouth (Fig. 3).

Stage 2. Segmentation of the region of interest

Upon receipt of the radiological data in DICOM format, one should define the region of interest (ROI) in two-dimensional projection (2D), or volume of interest (VOI) in three-dimensional (3D) projection begins. ROI/VOI determine the region in which the radiomic features are calculated. The image segmentation may be performed manually, semi-automatically or fully automatically (Fig. 4).

Stage 3. Extraction of radiomic features

After image segmentation and processing, the extraction of radiomic features can be performed, which is performed automatically after activation of the PyRadiomics module. The features extracted from images could be divided into morphological parameters (volume and shape), histogram features (description of gray tone intensities, texture analysis) (Fig. 5).

Stage 4. Obtaining imaging biomarkers

After receiving the radiomic data, selection or reduction of specific features is carried out. After that, the multivariate data analysis is started: a connection is established between the texture features of the gray level coincidence matrix and the morphological type of neoplasms. Isolated radiomic features that closely correlate with clinical findings may be assigned to the imaging biomarkers (Fig. 6).

Figure 4. Segmentation of the area of interest in 3D Slicer

Stage 5. Creation of a radiomally oriented augmented reality navigation system

To perform the surgery, two augmented reality markers were used. Marker 1 was attached to a holder embedded into the occlusal splint (as in cone-beam computer tomography?? CTCBCT). Marker 1 was associated with an image of a segmented neoplasm of the lower jaw with a highlighted visualization biomarker. Marker 2 was attached to the handle of the dental handpiece. Projection of the bone trephine was attached to marker 2 (Fig. 7 a, b).

Figure 7. Marker 1 fixed in the oral cavity (A); marker 2, at the dental handpiece (B)

Stage 6. Radiomic-guided biopsy of mandibular neoplasm in augmented reality

During the surgical intervention after fixation of the augmented reality markers, we checked calibration of the marker positions, projection of the lower jaw neoplasm, and the tip of the biopsy instrument. The surgery was performed under local anesthesia. Skeletonization of the outer plate of the lower jaw in the area 3.3-4.3 was performed. Bone tissue in the region under inspection had no visible abnormal changes (Fig. 8).

Figure 8. The body of the lower jaw in the projection of the neoplasm. Pathological changes are not visualized

The neoplasm imaging was made in augmented reality. Using a bone trephine, a fragment of the formation was sampled in projection of the imaging biomarker (Fig. 9).

Figure 9. Location of the neoplasm in virtual imaging (A), and actual location of the object (B)

The material was sent for histological examination. The postoperative period was uneventful.

Histological report was as follows: an area of fibrous dysplasia of the lower jaw.

Discussion

In the presented clinical case, according to the results of the radiomic analysis of the segmented neoplasm of the lower jaw, its distinctive radiomic features were revealed - imaging biomarkers, that were transferred to the surgical field using augmented reality technology.

The object of a lower jaw neoplasm obtained as a result of segmentation with a highlighted area of region biomarkers is combined with real anatomical structures in the oral cavity at the time of surgery by means of augmented reality technology. The combined model of this neoplasm demonstrates its anatomical and topographic position and structure, thus making it possible to determine the optimal operative access and most informative biopsy area for histological examination. Usage of this approach to tracking the instrument tip (bone trephine) in mixed reality enables control of its position, immersion depth, and reduced risk of traumas to adjacent anatomical structures. Real volume and topography of the object and adjacent anatomical structures fully corresponded to the data obtained in the course of virtual planning.

Conclusion

Analysis of medical images allows non-invasive assessment of the characteristics of human tissues. However, the interpretation of research results is often quite subjective. Recent advances in acquisition and analysis of medical imaging allow high-precision digital data extraction to quantify the difference between healthy and diseased tissue.

Radiomics applies mathematical analysis and advanced computational methodologies to medical imaging data to provide quantitative descriptors of pathological tissues. This is especially true for oncology.

Radiomics analysis of X-ray images has the potential to promote development of personalized medicine.

Clinical application of radiomic data is of the greatest interest for targeted biopsy of neoplasms in maxillofacial area. In order to improve accuracy of the diagnostic procedure, we recommend usage of augmented reality technology, which makes it possible to accurately visualize the most informative biopsy area for histological examination.

On the basis of advances in modern digital technologies such as radiomics and augmented reality, one can personalize and adapt established methods of treating diseases in the maxillofacial region for each patient, to improve the results of diagnosis and treatment, as well as reducing the number of complications.

References

Van Griethuysen JJM, Fedorov A, Parmar C, Hosny A, Aucoin N, Narayan V. Computational radiomics system to decode the radiographic phenotype. Cancer Research 2017; 77(21) :104-107. doi: 10.1158/0008-5472.CAN-17-0339
Aerts HJWL, Velazquez ER, Leijenaar RT, Parmar C, Grossmann P, Carvalho S. Decoding tumour phenotype by noninvasive imaging using a quantitative radiomics approach. Nature Сommun. 2014; 5(1): 1-9. doi: 10.1038/ncomms5006
Caudell JJ, Torres-Roca JF, Gillies RJ, Enderling H, Kim S, Rishi A, et al. The future of personalised radiotherapy for head and neck cancer. The Lancet Oncology 2017; 18( 5):266-273. doi: 10.1016/S1470-2045(17)30252-8
van Timmeren JE, Cester D, Tanadini-Lang S, Alkadhi H, Baessler B. Radiomics in medical imaging – "How-to" guide and critical reflection. Insights Imag. 2020; 11(1): 1-16. doi: 10.1186/s13244-020-00887-2
Yaremenko АI, Lysenko AV, Ivanova EA, Galibin OV. Augmented reality technology for auricular reconstruction in the treatment of microtia. Cell Ther Transplant. 2020; 9(2): 78-82. doi: 10.18620/ctt-1866-8836-2020-9-2-78-82
Lysenko AV, Razumova AYa, Yaremenko AI, Mirzakhmedov RR. Augmented reality in the treatment of sialolithiasis. Stomatology. 2020; 99(4): 64-66. doi: 10.17116/stomat20209904164

" ["~DETAIL_TEXT"]=> string(14372) "

Introduction

Figure 1. Algorithm for radiome analysis of Cone Beam Computed Tomography images and the algorithm for the operation of augmented reality technology (Original picture)

Materials and methods

Figure 2. Appearance of the software 3D Slicer

Stage 1. Acquisition of images using methods of radiology diagnostics

Figure 3. Appearance of the occlusal splint with X-ray contrast marks (A); Patient positioning at the cone-beam computed tomography with occlusal splint (B)

Stage 2. Segmentation of the region of interest

Stage 3. Extraction of radiomic features

Stage 4. Obtaining imaging biomarkers

Figure 4. Segmentation of the area of interest in 3D Slicer

Stage 5. Creation of a radiomally oriented augmented reality navigation system

Figure 7. Marker 1 fixed in the oral cavity (A); marker 2, at the dental handpiece (B)

Stage 6. Radiomic-guided biopsy of mandibular neoplasm in augmented reality

Figure 8. The body of the lower jaw in the projection of the neoplasm. Pathological changes are not visualized

The neoplasm imaging was made in augmented reality. Using a bone trephine, a fragment of the formation was sampled in projection of the imaging biomarker (Fig. 9).

Figure 9. Location of the neoplasm in virtual imaging (A), and actual location of the object (B)

The material was sent for histological examination. The postoperative period was uneventful.

Histological report was as follows: an area of fibrous dysplasia of the lower jaw.

Discussion

Conclusion

Radiomics analysis of X-ray images has the potential to promote development of personalized medicine.

References

Van Griethuysen JJM, Fedorov A, Parmar C, Hosny A, Aucoin N, Narayan V. Computational radiomics system to decode the radiographic phenotype. Cancer Research 2017; 77(21) :104-107. doi: 10.1158/0008-5472.CAN-17-0339
Aerts HJWL, Velazquez ER, Leijenaar RT, Parmar C, Grossmann P, Carvalho S. Decoding tumour phenotype by noninvasive imaging using a quantitative radiomics approach. Nature Сommun. 2014; 5(1): 1-9. doi: 10.1038/ncomms5006
Caudell JJ, Torres-Roca JF, Gillies RJ, Enderling H, Kim S, Rishi A, et al. The future of personalised radiotherapy for head and neck cancer. The Lancet Oncology 2017; 18( 5):266-273. doi: 10.1016/S1470-2045(17)30252-8
van Timmeren JE, Cester D, Tanadini-Lang S, Alkadhi H, Baessler B. Radiomics in medical imaging – "How-to" guide and critical reflection. Insights Imag. 2020; 11(1): 1-16. doi: 10.1186/s13244-020-00887-2
Yaremenko АI, Lysenko AV, Ivanova EA, Galibin OV. Augmented reality technology for auricular reconstruction in the treatment of microtia. Cell Ther Transplant. 2020; 9(2): 78-82. doi: 10.18620/ctt-1866-8836-2020-9-2-78-82
Lysenko AV, Razumova AYa, Yaremenko AI, Mirzakhmedov RR. Augmented reality in the treatment of sialolithiasis. Stomatology. 2020; 99(4): 64-66. doi: 10.17116/stomat20209904164

" ["DETAIL_TEXT_TYPE"]=> string(4) "html" ["~DETAIL_TEXT_TYPE"]=> string(4) "html" ["PREVIEW_TEXT"]=> string(0) "" ["~PREVIEW_TEXT"]=> string(0) "" ["PREVIEW_TEXT_TYPE"]=> string(4) "text" ["~PREVIEW_TEXT_TYPE"]=> string(4) "text" ["PREVIEW_PICTURE"]=> NULL ["~PREVIEW_PICTURE"]=> NULL ["LANG_DIR"]=> string(4) "/ru/" ["~LANG_DIR"]=> string(4) "/ru/" ["SORT"]=> string(2) "30" ["~SORT"]=> string(2) "30" ["CODE"]=> string(100) "opyt-primeneniya-radiomicheski-orientirovannoy-navigatsionnoy-sistemy-dopolnennoy-realnosti-pri-biop" ["~CODE"]=> string(100) "opyt-primeneniya-radiomicheski-orientirovannoy-navigatsionnoy-sistemy-dopolnennoy-realnosti-pri-biop" ["EXTERNAL_ID"]=> string(4) "2048" ["~EXTERNAL_ID"]=> string(4) "2048" ["IBLOCK_TYPE_ID"]=> string(7) "journal" ["~IBLOCK_TYPE_ID"]=> string(7) "journal" ["IBLOCK_CODE"]=> string(7) "volumes" ["~IBLOCK_CODE"]=> string(7) "volumes" ["IBLOCK_EXTERNAL_ID"]=> string(1) "2" ["~IBLOCK_EXTERNAL_ID"]=> string(1) "2" ["LID"]=> string(2) "s2" ["~LID"]=> string(2) "s2" ["EDIT_LINK"]=> NULL ["DELETE_LINK"]=> NULL ["DISPLAY_ACTIVE_FROM"]=> string(0) "" ["IPROPERTY_VALUES"]=> array(18) { ["ELEMENT_META_TITLE"]=> string(252) "Опыт применения радиомически-ориентированной навигационной системы дополненной реальности при биопсии новообразования нижней челюсти" ["ELEMENT_META_KEYWORDS"]=> string(0) "" ["ELEMENT_META_DESCRIPTION"]=> string(371) "Опыт применения радиомически-ориентированной навигационной системы дополненной реальности при биопсии новообразования нижней челюстиExperience in the use of a radio-oriented augmented reality navigation system for biopsy of a neoplasm of the lower jaw" ["ELEMENT_PREVIEW_PICTURE_FILE_ALT"]=> string(2286) "Радиомика – это количественный подход к медицинской визуализации, который направлен на улучшение существующих данных, доступных клиницистам, с помощью передового математического анализа. Посредством математического извлечения пространственного распределения интенсивностей сигналов и взаимосвязей пикселей, радиомика количественно определяет текстурную информацию, используя методы анализа из области искусственного интеллекта. Данные, извлеченные из рентгенологических изображений, при их сопоставлении с клиническими данными, потенциально могут предоставить дополнительную информацию для поддержки принятия решений в клинической медицине. В данном исследовании выполнен предварительный радиомический анализ новообразования нижней челюсти. На основании полученных данных произведен выбор оптимального участка для биопсии. Во время проведения диагностического вмешательства использовалась навигационная система дополненной реальности, которая учитывала результаты данного математического анализа. <h2>Ключевые слова</h2> Радиомика, дополненная реальность, динамические навигационные системы, новообразования челюстей." ["ELEMENT_PREVIEW_PICTURE_FILE_TITLE"]=> string(252) "Опыт применения радиомически-ориентированной навигационной системы дополненной реальности при биопсии новообразования нижней челюсти" ["ELEMENT_DETAIL_PICTURE_FILE_ALT"]=> string(252) "Опыт применения радиомически-ориентированной навигационной системы дополненной реальности при биопсии новообразования нижней челюсти" ["ELEMENT_DETAIL_PICTURE_FILE_TITLE"]=> string(252) "Опыт применения радиомически-ориентированной навигационной системы дополненной реальности при биопсии новообразования нижней челюсти" ["SECTION_META_TITLE"]=> string(252) "Опыт применения радиомически-ориентированной навигационной системы дополненной реальности при биопсии новообразования нижней челюсти" ["SECTION_META_KEYWORDS"]=> string(252) "Опыт применения радиомически-ориентированной навигационной системы дополненной реальности при биопсии новообразования нижней челюсти" ["SECTION_META_DESCRIPTION"]=> string(252) "Опыт применения радиомически-ориентированной навигационной системы дополненной реальности при биопсии новообразования нижней челюсти" ["SECTION_PICTURE_FILE_ALT"]=> string(252) "Опыт применения радиомически-ориентированной навигационной системы дополненной реальности при биопсии новообразования нижней челюсти" ["SECTION_PICTURE_FILE_TITLE"]=> string(252) "Опыт применения радиомически-ориентированной навигационной системы дополненной реальности при биопсии новообразования нижней челюсти" ["SECTION_PICTURE_FILE_NAME"]=> string(100) "opyt-primeneniya-radiomicheski-orientirovannoy-navigatsionnoy-sistemy-dopolnennoy-realnosti-pri-biop" ["SECTION_DETAIL_PICTURE_FILE_ALT"]=> string(252) "Опыт применения радиомически-ориентированной навигационной системы дополненной реальности при биопсии новообразования нижней челюсти" ["SECTION_DETAIL_PICTURE_FILE_TITLE"]=> string(252) "Опыт применения радиомически-ориентированной навигационной системы дополненной реальности при биопсии новообразования нижней челюсти" ["SECTION_DETAIL_PICTURE_FILE_NAME"]=> string(100) "opyt-primeneniya-radiomicheski-orientirovannoy-navigatsionnoy-sistemy-dopolnennoy-realnosti-pri-biop" ["ELEMENT_PREVIEW_PICTURE_FILE_NAME"]=> string(100) "opyt-primeneniya-radiomicheski-orientirovannoy-navigatsionnoy-sistemy-dopolnennoy-realnosti-pri-biop" ["ELEMENT_DETAIL_PICTURE_FILE_NAME"]=> string(100) "opyt-primeneniya-radiomicheski-orientirovannoy-navigatsionnoy-sistemy-dopolnennoy-realnosti-pri-biop" } ["FIELDS"]=> array(1) { ["IBLOCK_SECTION_ID"]=> string(3) "203" } ["PROPERTIES"]=> array(18) { ["KEYWORDS"]=> array(36) { ["ID"]=> string(2) "19" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:46:01" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(27) "Ключевые слова" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(8) "KEYWORDS" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "Y" ["XML_ID"]=> string(2) "19" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "4" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "Y" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "Y" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> bool(false) ["VALUE"]=> bool(false) ["DESCRIPTION"]=> bool(false) ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> bool(false) ["~DESCRIPTION"]=> bool(false) ["~NAME"]=> string(27) "Ключевые слова" ["~DEFAULT_VALUE"]=> string(0) "" } ["SUBMITTED"]=> array(36) { ["ID"]=> string(2) "20" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(21) "Дата подачи" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "SUBMITTED" ["DEFAULT_VALUE"]=> NULL ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "20" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> NULL ["VALUE"]=> string(0) "" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(0) "" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(21) "Дата подачи" ["~DEFAULT_VALUE"]=> NULL } ["ACCEPTED"]=> array(36) { ["ID"]=> string(2) "21" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(25) "Дата принятия" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(8) "ACCEPTED" ["DEFAULT_VALUE"]=> NULL ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "21" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> NULL ["VALUE"]=> string(0) "" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(0) "" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(25) "Дата принятия" ["~DEFAULT_VALUE"]=> NULL } ["PUBLISHED"]=> array(36) { ["ID"]=> string(2) "22" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(29) "Дата публикации" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "PUBLISHED" ["DEFAULT_VALUE"]=> NULL ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "22" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> NULL ["VALUE"]=> string(0) "" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(0) "" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(29) "Дата публикации" ["~DEFAULT_VALUE"]=> NULL } ["CONTACT"]=> array(36) { ["ID"]=> string(2) "23" ["TIMESTAMP_X"]=> string(19) "2015-09-03 14:43:05" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(14) "Контакт" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "CONTACT" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "23" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "3" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "N" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> NULL ["VALUE"]=> string(0) "" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(0) "" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(14) "Контакт" ["~DEFAULT_VALUE"]=> string(0) "" } ["AUTHORS"]=> array(36) { ["ID"]=> string(2) "24" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:45:07" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Авторы" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "AUTHORS" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "Y" ["XML_ID"]=> string(2) "24" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "3" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "N" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> bool(false) ["VALUE"]=> bool(false) ["DESCRIPTION"]=> bool(false) ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> bool(false) ["~DESCRIPTION"]=> bool(false) ["~NAME"]=> string(12) "Авторы" ["~DEFAULT_VALUE"]=> string(0) "" } ["AUTHOR_RU"]=> array(36) { ["ID"]=> string(2) "25" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Авторы" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "AUTHOR_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "25" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28485" ["VALUE"]=> array(2) { ["TEXT"]=> string(310) "Анна В. Лысенко1, Андрей И. Яременко2, Владимир М. Иванов3, Сергей В. Стрелков3, Елизавета А. Иванова2" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(238) "

Анна В. Лысенко¹, Андрей И. Яременко², Владимир М. Иванов³, Сергей В. Стрелков³, Елизавета А. Иванова²

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Авторы" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["ORGANIZATION_RU"]=> array(36) { ["ID"]=> string(2) "26" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(22) "Организации" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "26" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28486" ["VALUE"]=> array(2) { ["TEXT"]=> string(751) "1 Отдел челюстно-лицевой хирургии НИИ стоматологии и челюстно-лицевой хирургии, Санкт-Петербург, Россия 2 Кафедра челюстно-лицевой хирургии, Первый Санкт-Петербургский государственный медицинский университет им. акад. И. П. Павлова, Санкт-Петербург, Россия 3 Санкт-Петербургский политехнический университет Петра Великого, Санкт-Петербург, Россия" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(691) "

¹ Отдел челюстно-лицевой хирургии НИИ стоматологии и челюстно-лицевой хирургии, Санкт-Петербург, Россия
² Кафедра челюстно-лицевой хирургии, Первый Санкт-Петербургский государственный медицинский университет им. акад. И. П. Павлова, Санкт-Петербург, Россия
³ Санкт-Петербургский политехнический университет Петра Великого, Санкт-Петербург, Россия

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(22) "Организации" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["SUMMARY_RU"]=> array(36) { ["ID"]=> string(2) "27" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(29) "Описание/Резюме" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "27" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28487" ["VALUE"]=> array(2) { ["TEXT"]=> string(2286) "Радиомика – это количественный подход к медицинской визуализации, который направлен на улучшение существующих данных, доступных клиницистам, с помощью передового математического анализа. Посредством математического извлечения пространственного распределения интенсивностей сигналов и взаимосвязей пикселей, радиомика количественно определяет текстурную информацию, используя методы анализа из области искусственного интеллекта. Данные, извлеченные из рентгенологических изображений, при их сопоставлении с клиническими данными, потенциально могут предоставить дополнительную информацию для поддержки принятия решений в клинической медицине. В данном исследовании выполнен предварительный радиомический анализ новообразования нижней челюсти. На основании полученных данных произведен выбор оптимального участка для биопсии. Во время проведения диагностического вмешательства использовалась навигационная система дополненной реальности, которая учитывала результаты данного математического анализа. <h2>Ключевые слова</h2> Радиомика, дополненная реальность, динамические навигационные системы, новообразования челюстей." ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(2208) "

Радиомика – это количественный подход к медицинской визуализации, который направлен на улучшение существующих данных, доступных клиницистам, с помощью передового математического анализа. Посредством математического извлечения пространственного распределения интенсивностей сигналов и взаимосвязей пикселей, радиомика количественно определяет текстурную информацию, используя методы анализа из области искусственного интеллекта. Данные, извлеченные из рентгенологических изображений, при их сопоставлении с клиническими данными, потенциально могут предоставить дополнительную информацию для поддержки принятия решений в клинической медицине.

В данном исследовании выполнен предварительный радиомический анализ новообразования нижней челюсти. На основании полученных данных произведен выбор оптимального участка для биопсии. Во время проведения диагностического вмешательства использовалась навигационная система дополненной реальности, которая учитывала результаты данного математического анализа.

Ключевые слова

Радиомика, дополненная реальность, динамические навигационные системы, новообразования челюстей.

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(29) "Описание/Резюме" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["DOI"]=> array(36) { ["ID"]=> string(2) "28" ["TIMESTAMP_X"]=> string(19) "2016-04-06 14:11:12" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(3) "DOI" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(3) "DOI" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "28" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28488" ["VALUE"]=> string(40) "10.18620/ctt-1866-8836-2021-10-3-4-78-83" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(40) "10.18620/ctt-1866-8836-2021-10-3-4-78-83" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(3) "DOI" ["~DEFAULT_VALUE"]=> string(0) "" } ["AUTHOR_EN"]=> array(36) { ["ID"]=> string(2) "37" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(6) "Author" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "AUTHOR_EN" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "37" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28489" ["VALUE"]=> array(2) { ["TEXT"]=> string(238) "Anna V. Lysenko1, Andrey I. Yaremenko2, Vladimir M. Ivanov3, Sergey V. Strelkov3, Elizaveta A. Ivanova2 " ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(166) "

Anna V. Lysenko¹, Andrey I. Yaremenko², Vladimir M. Ivanov³, Sergey V. Strelkov³, Elizaveta A. Ivanova²

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(6) "Author" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["ORGANIZATION_EN"]=> array(36) { ["ID"]=> string(2) "38" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Organization" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_EN" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "38" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28490" ["VALUE"]=> array(2) { ["TEXT"]=> string(1002) "1 Department of Maxillofacial Surgery, Research Institute of Dentistry and Maxillofacial Surgery, St. Petersburg, Russia 2 Department of Maxillofacial Surgery, Pavlov University, St. Petersburg, Russia 3 Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russia Correspondence: Dr. Anna V. Lysenko, Department of Maxillofacial Surgery, Research Institute of Dentistry and Maxillofacial Surgery, Pavlov University, 44 Petrogradskaya Emb., 197101, St. Petersburg, Russia Phone: +7 (812) 429-03-33 E-mail: lysenko.anna@mail.ru Citation: Lysenko AV, Yaremenko AI, Ivanov VM et al. Experience in the use of a radio-oriented augmented reality navigation system for biopsy of a neoplasm of the lower jaw. Cell Ther Transplant 2021; 10(3-4): 78-83." ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(864) "

¹ Department of Maxillofacial Surgery, Research Institute of Dentistry and Maxillofacial Surgery, St. Petersburg, Russia
² Department of Maxillofacial Surgery, Pavlov University, St. Petersburg, Russia
³ Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russia

Correspondence:
Dr. Anna V. Lysenko, Department of Maxillofacial Surgery, Research Institute of Dentistry and Maxillofacial Surgery, Pavlov University, 44 Petrogradskaya Emb., 197101, St. Petersburg, Russia
Phone: +7 (812) 429-03-33
E-mail: lysenko.anna@mail.ru

Citation: Lysenko AV, Yaremenko AI, Ivanov VM et al. Experience in the use of a radio-oriented augmented reality navigation system for biopsy of a neoplasm of the lower jaw. Cell Ther Transplant 2021; 10(3-4): 78-83.

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Organization" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["SUMMARY_EN"]=> array(36) { ["ID"]=> string(2) "39" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(21) "Description / Summary" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_EN" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "39" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28491" ["VALUE"]=> array(2) { ["TEXT"]=> string(1153) "Radiomics is a quantitative approach to medical imaging that applies advanced mathematical analysis in order to improve the existing data available to clinicians. Radiomics quantifies texture information by mathematical extraction of spatial distribution of the signal intensities and pixel relationships. Quantitative evaluation of the texture 2-D information employs analytic techniques from the field of artificial intelligence. The data derived from radiographic images, when compared with clinical data, may potentially provide additional information aiming for support of decision-making in clinical medicine. In this study, a preliminary radiomic analysis of a lower jaw neoplasm was performed. Based on the data obtained, the optimal site for tissue biopsy was chosen. During diagnostic intervention, an augmented reality navigation system was used which took into account the results of the mentioned mathematical analysis. <h2>Keywords</h2> Radiomics, augmented reality, dynamic navigation systems, jaw neoplasms." ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(1097) "

Radiomics is a quantitative approach to medical imaging that applies advanced mathematical analysis in order to improve the existing data available to clinicians. Radiomics quantifies texture information by mathematical extraction of spatial distribution of the signal intensities and pixel relationships. Quantitative evaluation of the texture 2-D information employs analytic techniques from the field of artificial intelligence. The data derived from radiographic images, when compared with clinical data, may potentially provide additional information aiming for support of decision-making in clinical medicine. In this study, a preliminary radiomic analysis of a lower jaw neoplasm was performed. Based on the data obtained, the optimal site for tissue biopsy was chosen. During diagnostic intervention, an augmented reality navigation system was used which took into account the results of the mentioned mathematical analysis.

Keywords

Radiomics, augmented reality, dynamic navigation systems, jaw neoplasms.

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(21) "Description / Summary" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["NAME_EN"]=> array(36) { ["ID"]=> string(2) "40" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:49:47" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(4) "Name" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "NAME_EN" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "40" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28492" ["VALUE"]=> string(119) "Experience in the use of a radio-oriented augmented reality navigation system for biopsy of a neoplasm of the lower jaw" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(119) "Experience in the use of a radio-oriented augmented reality navigation system for biopsy of a neoplasm of the lower jaw" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(4) "Name" ["~DEFAULT_VALUE"]=> string(0) "" } ["FULL_TEXT_RU"]=> &array(36) { ["ID"]=> string(2) "42" ["TIMESTAMP_X"]=> string(19) "2015-09-07 20:29:18" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(23) "Полный текст" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(12) "FULL_TEXT_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "42" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> NULL ["VALUE"]=> string(0) "" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(0) "" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(23) "Полный текст" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["PDF_RU"]=> array(36) { ["ID"]=> string(2) "43" ["TIMESTAMP_X"]=> string(19) "2015-09-09 16:05:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(7) "PDF RUS" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(6) "PDF_RU" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "F" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "43" ["FILE_TYPE"]=> string(18) "doc, txt, rtf, pdf" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28493" ["VALUE"]=> string(4) "2750" ["DESCRIPTION"]=> NULL ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(4) "2750" ["~DESCRIPTION"]=> NULL ["~NAME"]=> string(7) "PDF RUS" ["~DEFAULT_VALUE"]=> string(0) "" } ["PDF_EN"]=> array(36) { ["ID"]=> string(2) "44" ["TIMESTAMP_X"]=> string(19) "2015-09-09 16:05:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(7) "PDF ENG" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(6) "PDF_EN" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "F" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "44" ["FILE_TYPE"]=> string(18) "doc, txt, rtf, pdf" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28494" ["VALUE"]=> string(4) "2751" ["DESCRIPTION"]=> NULL ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(4) "2751" ["~DESCRIPTION"]=> NULL ["~NAME"]=> string(7) "PDF ENG" ["~DEFAULT_VALUE"]=> string(0) "" } ["NAME_LONG"]=> array(36) { ["ID"]=> string(2) "45" ["TIMESTAMP_X"]=> string(19) "2023-04-13 00:55:00" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(72) "Название (для очень длинных заголовков)" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "NAME_LONG" ["DEFAULT_VALUE"]=> array(2) { ["TYPE"]=> string(4) "HTML" ["TEXT"]=> string(0) "" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "45" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(80) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> NULL ["VALUE"]=> string(0) "" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(0) "" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(72) "Название (для очень длинных заголовков)" ["~DEFAULT_VALUE"]=> array(2) { ["TYPE"]=> string(4) "HTML" ["TEXT"]=> string(0) "" } } } ["DISPLAY_PROPERTIES"]=> array(8) { ["AUTHOR_EN"]=> array(37) { ["ID"]=> string(2) "37" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(6) "Author" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "AUTHOR_EN" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "37" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28489" ["VALUE"]=> array(2) { ["TEXT"]=> string(238) "Anna V. Lysenko1, Andrey I. Yaremenko2, Vladimir M. Ivanov3, Sergey V. Strelkov3, Elizaveta A. Ivanova2 " ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(166) "

Anna V. Lysenko¹, Andrey I. Yaremenko², Vladimir M. Ivanov³, Sergey V. Strelkov³, Elizaveta A. Ivanova²

" } ["SUMMARY_EN"]=> array(37) { ["ID"]=> string(2) "39" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(21) "Description / Summary" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_EN" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "39" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28491" ["VALUE"]=> array(2) { ["TEXT"]=> string(1153) "Radiomics is a quantitative approach to medical imaging that applies advanced mathematical analysis in order to improve the existing data available to clinicians. Radiomics quantifies texture information by mathematical extraction of spatial distribution of the signal intensities and pixel relationships. Quantitative evaluation of the texture 2-D information employs analytic techniques from the field of artificial intelligence. The data derived from radiographic images, when compared with clinical data, may potentially provide additional information aiming for support of decision-making in clinical medicine. In this study, a preliminary radiomic analysis of a lower jaw neoplasm was performed. Based on the data obtained, the optimal site for tissue biopsy was chosen. During diagnostic intervention, an augmented reality navigation system was used which took into account the results of the mentioned mathematical analysis. <h2>Keywords</h2> Radiomics, augmented reality, dynamic navigation systems, jaw neoplasms." ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(1097) "

Keywords

Radiomics, augmented reality, dynamic navigation systems, jaw neoplasms.

Keywords

Radiomics, augmented reality, dynamic navigation systems, jaw neoplasms.

" } ["DOI"]=> array(37) { ["ID"]=> string(2) "28" ["TIMESTAMP_X"]=> string(19) "2016-04-06 14:11:12" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(3) "DOI" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(3) "DOI" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "28" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28488" ["VALUE"]=> string(40) "10.18620/ctt-1866-8836-2021-10-3-4-78-83" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(40) "10.18620/ctt-1866-8836-2021-10-3-4-78-83" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(3) "DOI" ["~DEFAULT_VALUE"]=> string(0) "" ["DISPLAY_VALUE"]=> string(40) "10.18620/ctt-1866-8836-2021-10-3-4-78-83" } ["NAME_EN"]=> array(37) { ["ID"]=> string(2) "40" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:49:47" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(4) "Name" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "NAME_EN" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "40" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28492" ["VALUE"]=> string(119) "Experience in the use of a radio-oriented augmented reality navigation system for biopsy of a neoplasm of the lower jaw" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(119) "Experience in the use of a radio-oriented augmented reality navigation system for biopsy of a neoplasm of the lower jaw" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(4) "Name" ["~DEFAULT_VALUE"]=> string(0) "" ["DISPLAY_VALUE"]=> string(119) "Experience in the use of a radio-oriented augmented reality navigation system for biopsy of a neoplasm of the lower jaw" } ["ORGANIZATION_EN"]=> array(37) { ["ID"]=> string(2) "38" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Organization" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_EN" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "38" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28490" ["VALUE"]=> array(2) { ["TEXT"]=> string(1002) "1 Department of Maxillofacial Surgery, Research Institute of Dentistry and Maxillofacial Surgery, St. Petersburg, Russia 2 Department of Maxillofacial Surgery, Pavlov University, St. Petersburg, Russia 3 Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russia Correspondence: Dr. Anna V. Lysenko, Department of Maxillofacial Surgery, Research Institute of Dentistry and Maxillofacial Surgery, Pavlov University, 44 Petrogradskaya Emb., 197101, St. Petersburg, Russia Phone: +7 (812) 429-03-33 E-mail: lysenko.anna@mail.ru Citation: Lysenko AV, Yaremenko AI, Ivanov VM et al. Experience in the use of a radio-oriented augmented reality navigation system for biopsy of a neoplasm of the lower jaw. Cell Ther Transplant 2021; 10(3-4): 78-83." ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(864) "

" } ["AUTHOR_RU"]=> array(37) { ["ID"]=> string(2) "25" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Авторы" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "AUTHOR_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "25" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28485" ["VALUE"]=> array(2) { ["TEXT"]=> string(310) "Анна В. Лысенко1, Андрей И. Яременко2, Владимир М. Иванов3, Сергей В. Стрелков3, Елизавета А. Иванова2" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(238) "

Анна В. Лысенко¹, Андрей И. Яременко², Владимир М. Иванов³, Сергей В. Стрелков³, Елизавета А. Иванова²

" } ["SUMMARY_RU"]=> array(37) { ["ID"]=> string(2) "27" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(29) "Описание/Резюме" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "27" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28487" ["VALUE"]=> array(2) { ["TEXT"]=> string(2286) "Радиомика – это количественный подход к медицинской визуализации, который направлен на улучшение существующих данных, доступных клиницистам, с помощью передового математического анализа. Посредством математического извлечения пространственного распределения интенсивностей сигналов и взаимосвязей пикселей, радиомика количественно определяет текстурную информацию, используя методы анализа из области искусственного интеллекта. Данные, извлеченные из рентгенологических изображений, при их сопоставлении с клиническими данными, потенциально могут предоставить дополнительную информацию для поддержки принятия решений в клинической медицине. В данном исследовании выполнен предварительный радиомический анализ новообразования нижней челюсти. На основании полученных данных произведен выбор оптимального участка для биопсии. Во время проведения диагностического вмешательства использовалась навигационная система дополненной реальности, которая учитывала результаты данного математического анализа. <h2>Ключевые слова</h2> Радиомика, дополненная реальность, динамические навигационные системы, новообразования челюстей." ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(2208) "

Ключевые слова

Радиомика, дополненная реальность, динамические навигационные системы, новообразования челюстей.

Ключевые слова

Радиомика, дополненная реальность, динамические навигационные системы, новообразования челюстей.

" } ["ORGANIZATION_RU"]=> array(37) { ["ID"]=> string(2) "26" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(22) "Организации" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "26" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28486" ["VALUE"]=> array(2) { ["TEXT"]=> string(751) "1 Отдел челюстно-лицевой хирургии НИИ стоматологии и челюстно-лицевой хирургии, Санкт-Петербург, Россия 2 Кафедра челюстно-лицевой хирургии, Первый Санкт-Петербургский государственный медицинский университет им. акад. И. П. Павлова, Санкт-Петербург, Россия 3 Санкт-Петербургский политехнический университет Петра Великого, Санкт-Петербург, Россия" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(691) "

" } } } [1]=> array(49) { ["IBLOCK_SECTION_ID"]=> string(3) "203" ["~IBLOCK_SECTION_ID"]=> string(3) "203" ["ID"]=> string(4) "2047" ["~ID"]=> string(4) "2047" ["IBLOCK_ID"]=> string(1) "2" ["~IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(191) "СаСО3 ватериты, покрытые декстрансульфатом, как системы для регионарного введения доксорубицина крысам" ["~NAME"]=> string(191) "СаСО3 ватериты, покрытые декстрансульфатом, как системы для регионарного введения доксорубицина крысам" ["ACTIVE_FROM"]=> NULL ["~ACTIVE_FROM"]=> NULL ["TIMESTAMP_X"]=> string(22) "01/26/2022 12:10:25 pm" ["~TIMESTAMP_X"]=> string(22) "01/26/2022 12:10:25 pm" ["DETAIL_PAGE_URL"]=> string(161) "/en/archive/tom-10-nomer-3-4/eksperimentalnye-issledovaniya/saso3-vaterity-pokrytye-dekstransulfatom-kak-sistemy-dlya-regionarnogo-vvedeniya-doksorubitsina-krys/" ["~DETAIL_PAGE_URL"]=> string(161) "/en/archive/tom-10-nomer-3-4/eksperimentalnye-issledovaniya/saso3-vaterity-pokrytye-dekstransulfatom-kak-sistemy-dlya-regionarnogo-vvedeniya-doksorubitsina-krys/" ["LIST_PAGE_URL"]=> string(12) "/en/archive/" ["~LIST_PAGE_URL"]=> string(12) "/en/archive/" ["DETAIL_TEXT"]=> string(31571) "

Introduction

Doxorubicin is a very potent anticancer antibiotic that, unfortunately, demonstrates considerable cardiotoxicity, accumulation in liver and rapid clearance [1]. Use of various delivery systems for DOX in chemotherapy makes it possible to decrease negative influence of the drug and provides its prolonged release. In our previous work [2], it has been shown that porous carbonate vaterites modified with various polyanions can be successfully applied for encapsulation of DOX and facilitate prolonged in vitro release of the substance into blood plasma. Besides, it has been proven that these delivery systems (DS) are bio-resorbable and safe to use [3, 4]. The advantages of these DS in chemotherapy are related to some peculiar features of defense mechanisms of tumor cells against chemotherapeutic compounds. Drug efflux is among these mechanisms which does not affect DS (unlike free DOX). Phagocytosis of drugs by a cell is preceded by opsonization. Mechanism of opsonization (sorption of various plasma components on surface of delivery system) is impaired when a DOX-containing DS is coated with polyelectrolytes. As a result, opsonization is reduced, and the time of passive DS circulation is prolonged in the area of high capillary permeability and disturbed lymphatic drainage (typical of tumor tissues [5]); i.e., the drug is retained in the tumor tissue.

Among other delivery systems for DOX, polymer-drug conjugates (PDC) have been described [6]. In our earlier work [2], the profiles of DOX release into blood plasma have been compared for PDC (DexS+DOX) versus DexS coated СаСО₃ cores.

Ascitic tumors (particularly, Seidel hepatoma, SH) are widely used as models for in vivo studies of regional intraperitoneal chemotherapy. These tumors are included into the list recommended by the Russian Ministry of Health and the State Pharmacological Committee for studies of antitumor mechanisms [7].

Revtovich et al. [8] compared antitumor activity of cisplatin and its prolonged pharmaceutical form based on dextran phosphate hydrogel in the rats inoculated with Seidel hepatoma. They have demonstrated higher efficiency of the modified drug.

When free DOX or DOX-containing delivery systems are used in chemotherapy, it is important to control concentration of the substance in blood. Administration of free DOX results in its distribution through all the organs and tissues. When delivery systems are used, distribution of the drug in organism largely depends on DS structure (i.e., drug release rate) and its administration route (intravenous, intraperitoneal, subcutaneous, etc. [9]). The amount of introduced drug and physiology of an organism are also of importance.

Comparing the literature data on DOX concentration in blood plasma after intravenous administration to different tumor-bearing mice and women, we can see that the amount of introduced DOX exerts relatively low influence on its content in plasma, whereas tumor type is a considerable factor [10-13].

The aims of the present work included (i) studies of the opportunity to use the proposed delivery model of antitumor preparation in laboratory animals; (ii) time course evaluation of DOX release into blood following intraperitoneal administration, using drug delivery systems based on CaCO₃ cores coated with DexS, or DexS-DOX conjugates (HPLC studies of DOX release); (iii) comparison between the profiles of DOX release into rat blood (both in healthy rats and animals with Seidel hepatoma), and general condition of animals, thus discerning effects of the released DOX amounts upon malignant cells in tumor-bearing animals and upon intact rats.

Materials and methods

Reagents

Doxorubicin hydrochloride purchased as the “Sindroxocin” preparation, containing 17% of doxorubicin (DOX) and 83% of lactose, was from Actavis (Hafnarfjordur, Iceland). For experiments, doxorubicin salt with protonated amino group (–NH3⁺) was used. Salts (CaCl₂ × 2H₂O, Na₂CO₃), acetone, and dextran sulfate (M_w = 9-20 kDa) were purchased from Sigma-Aldrich (St. Louis, MO).

Synthesis of carbonate cores

Preparation techniques for porous carbonate vaterites, methods for coating vaterites with DexS polyanion and introducing DOX into these carriers are described in [14]. Briefly, porous vaterites (СаСО₃ cores) were prepared by co-precipitation. Equal volumes of 1 M aqueous solutions of CaCl₂ × 2H₂O and Na₂CO₃ were rapidly mixed at stirring (1000 rpm) with an RW 20 anchor-type mechanical stirrer (Kika-Werk, Switzerland). The mixture was stirred for 30 s. The suspension was then filtered through Schott filter glass (#16), washed thrice with distilled water and with acetone/water mixtures with increasing acetone concentrations (33%, 50%, and 100%). The precipitate was dried in thermostat at 40-50°C until a constant weight was achieved.

Doping of carbonate cores with DexS and DOX loading into delivery systems

The cores were coated with a polyanion (sodium salt of dextran sulfate, DexS). СаСО₃ cores (50 mg) were added to 1 mg/mL aqueous solution of DexS (10 mL). The suspension was stirred using a Multi Bio RS-24 rotor (Biosan, Latvia) for 1 h; the solid fraction was filtered off using a Schott glass filter (#16), washed thrice with distilled water and dried at 30°C.

DOX was loaded into doped CaCO₃ under continuous stirring of the mixture of CaCO₃ suspension and DOX solution (C=2 mg/mL) for 24 hours. The DOX/(CaCO₃+DexS) ratio was 0.4. After mixing, the suspension was centrifuged at 8000 rpm for 3 min, and the DOX amount in supernatant was determined.

DOX load (L) was calculated using the following equation: L = (m_i − m_s)/m_P, where m_i is the initial amount of DOX (mg), m_s is the amount of non-encapsulated DOX in supernatant solution (mg), m_P is the amount of particles (mg).

DOX concentrations were determined using the calibration curves obtained from optical density measurements in the corresponding solvents at λ=480 nm. The measurements were carried out using a SF-2000 spectrophotometer (LOMO, St. Petersburg, Russia).

Polymer-drug conjugates and their loading

Polymer-drug conjugates (DexS+DOX) were prepared according to the technique described in [2]. The DOX solution (2 mg/mL) and solution of DexS polyanion (1 mg/mL) were mixed in volumes that provided an equimolar ratio of functional groups. Then the mixture was subjected to ultrasound treatment for 2 min and centrifuged at 8000 rpm for 10 min. The supernatant was removed, the residue was freeze-dried. The DOX concentration in supernatant was determined spectrophotometrically. The PDC load was determined by subtracting the amount of DOX in supernatant from total amount of introduced DOX followed by dividing this quantity by the weight of the residue. All the measurements were carried out thrice.

In vivo experiments with rats

Two groups of rats were used in the experiments with intraperitoneal administration of various DOX delivery systems. The first group (experimental) included the rats with inoculated Seidel hepatoma; DOX encapsulated into calcium carbonate cores doped with DexS polyanion was administrated intraperitoneally (i.p.). The second group consisted of healthy rats; they were treated i.p. with DOX incorporated into different delivery systems: (i) submicron-sized calcium carbonate cores coated with DexS polyanion (CaCO₃+DexS); (ii) nanosized polymer-drug conjugates (DexS+DOX). Two reference groups were also included, i.e., the first reference group consisted of non-treated animals with inoculated Seidel hepatoma (no DOX included in the СаСО₃+DexS delivery system was introduced). The second reference group consisted of healthy rats that were treated with free DOX (without delivery systems).

Thirty-six male and female outbred rats with body weight ranging from 256 to 312 g were used in the experiments ("Rappolovo" nursery for laboratory animals). All manipulations with animals were performed under general anesthesia: Sol. Zoletil 50 (0.05 mL per 0.1 kg of body mass), Sol. Rometаrum 20 mg/mL (0.0125 mL per 0.1 kg of body mass, intramuscularly). The animals were caged (2-5 individuals in a cage), had free access to water and food (4R F18 prolonged keeping formula for rodents, Macedonia, Italy). The animals were fed the standard diet for laboratory rats used in the vivarium of A. M. Granov Russian Research Center of Radiology and Surgical Technologies, St. Petersburg, Russia.

The animals of experimental and reference groups were examined daily; consumption of water and food was registered, body temperature and weight were measured. Behavior of animals and life expectancy were estimated. Immediately after death, ascitic fluid was collected, and its volume was determined. All the manipulations with animals were performed in accordance with State Standard 33216-2014 "Regulations for work with laboratory rodents and rabbits".

Transplantation of ascitic Seidel hepatoma (SH)

Resuspended cells of ascitic Seidel hepatoma (freshly defrosted and washed from dimethyl sulfoxide) were injected into abdominal cavity of rats from the 1^st group. Ascitic fluid containing Seidel hepatoma cells (1 mL) was introduced intraperitoneally using a needle (21 G). The dosage was calculated using the Freireich quotient [15].

Introduction of DOX into rats

Doxorubicin (both free and encapsulated in delivery systems) was administered to anaesthesized animals using Zoletil 50, 0.05 mL per 0.1 kg of body mass i.p.). The drug was injected in 1.5 mL of 5% glucose solution, containing DOX in CаСО₃+DexS cores, or DOX in polymer drug conjugates (DexS+DOX), or free DOX (2 or 4 mg of DOX per 1 animal of the 1^st and 2^nd groups, respectively). The drug preparations were injected by means of 21-gauge needles. For the animals of the 1^st experimental group, the tumor cells and DOX-containing delivery systems were applied simultaneously. Examination of animals from the 1^st group was described elsewhere ("In vivo experiments with rats").

Along with visual inspection, peripheral blood (1.0 mL) was taken from tail vein of rats of the 1^st group 24 h, at 4, 7, 14, 17 and 21 days after drug injection. Before blood sampling, the rat was examined, weighed, its body temperature was measured, then it was anesthetized and fixed in a holder for immobilizing rodents. Plasma was obtained from the blood specimens 10 min after blood sampling by centrifugation for 15 min at 1500 rpm. The supernatantses were frozen and stored in closed vessels at -40°C for further analysis.

Determination of DOX content in plasma of rats

Content of doxorubicin (DOX) in rat blood plasma was determined by high-performance liquid chromatography (HPLC) using Prominence-I LC 2030C 3D Plus instrument (Shimadzu) equipped with an RF-20A fluorimetric detector and a 5 µm Luna C18 column (Phenomenex). The excitation wavelength was 475 nm, emission wavelength was 555 nm. Analysis was performed in the gradient elution regime (with acetonitrile) in 0.01 N Na-formiate buffer (рН 3.68). Duration of experiment: was 20 min, at the detection limit of 1 ng/mL. All the measurements were carried out thrice.

Results and discussion

First group of rats

The influence of DOX delivery systems based on porous calcium carbonate cores coated with DexS (CaCO₃+DexS) on development of Seidel hepatoma was studied in laboratory rats.

The first experimental group included 4 male and 4 female rats with body mass varying from 256 to 306 g. The first reference group consisted of 5 male and 3 female animals (266 to 312 g). The animals were followed up as described under Materials and Methods.

Six animals from the first experimental group died within a period from 10 to 14 days after the procedure (median, 14 days). All animals of the reference group died within a period from 8 to 13 days after the beginning of the experiment; the lifetime median was 8 days. Physical examination revealed ascites in animals of both groups starting from the 4^th day after starting the experiment. The volume of ascites determined during autopsy in the reference group varied from 31 to 122 mL (median, 66 mL), compared with volume of 28 to 34 mL (median: 31 mL) in the 1^st experimental group. The difference in ascites volumes between the two groups was statistically significant (р <0.05, according to the Mann-Whitney criterion). Two animals from the first experimental group survived for more than two weeks and were withdrawn from the experiment on day 207.

Changes in appearance and behavior of animals of the reference group were seen at 8 days and were observed for 2-3 days until death of animals. Their fur became lackluster and scraggly. The animals were depressed, lacking curiosity and reaction to other animals, low motor activity, with absence of vertical postures. The amount of consumed food decreased, whereas the amount of consumed water remained the same. If an animal died within 8 days after injecting hepatoma cells, the above changes were not observed.

In the animals treated with doxorubicin (the 1^st experimental group), exterior and behavior started to change later (in 10 days). The changes in fur appearance were similar to those in reference group. The animals were depressed, moved slowly (crawled); reddish eyelids and developed yellowish crusts (simple blepharitis) were observed. Of note, no eye pathology was seen in the animals of the reference group. Two animals of experimental group that died within 10 days after treatment did not show these changes.

In two surviving animals from the 1^st experimental group (that survived for 207 days after implantation of hepatoma cells and injection of DOX in CaCO₃+DexS delivery systems), ascites was revealed in 4 days (physical examination). From 10 to 14 days of the experiment, changed appearance (dull and scraggly fur), behavior and motion activity (depression, absence of vertical postures) were observed. Slight reddening of eyelids, decrease in food consumption and weight loss also occurred. Then the above sickness symptoms disappeared, the animals started to feed normally and gained weight. No signs of Seidel hepatoma and ascites were revealed during autopsy.

The observations described above allowed us to make the following conclusions: DOX applied intraperitoneally in the DS based on calcium carbonate cores doped with DexS affects development of the tumor, manifesting as decreased volume of ascitic fluid. Low percentage of survival (only two animals) may be explained by low dose of antitumor preparation (2 mg per animal). In this series of experiments, concentrations of doxorubicin in blood were not determined.

Since the animals tolerated treatment with DOX in (CaCO₃+DexS) delivery systems relatively well, and the applied dose (2 mg of doxorubicin per animal) inhibited development of Seidel hepatoma, one may assume that the amount of injected preparation in DS can be increased. Therefore, the next experiment with laboratory animals was designed.

Second group of rats

Time dynamics of DOX release in blood of laboratory animals after i.p. administration of two types of delivery systems were studied. The two kinds of delivery systems were used: porous calcium carbonate cores doped with DexS (CaCO₃+DexS) (DS1), and DexS-DOX conjugates (DS2).

The 2^nd experimental group of rats included 17 healthy animals (body weight 270-310 g). Six rats (2 females, 4 males) were treated with DOX in DS1 (4 mg per animal); the remaining eleven animals (6 females, 5 males) were treated with DOX in DS2 (4 mg of DOX per animal). The 2^nd reference group for treatment with free DOX consisted of 3 rats (2 females, 1 male) weighing from 260 to 280 g.

Upon i.p. administration of CаСО₃+DexS delivery systems containing DOX, the animals were active, no inflammation symptoms were observed in the injection area. During the experiment, no changes in the state of fur, eyes, neither abnormal behavior nor reactions were registered. The body temperature was typical of healthy rats. Starting from the 2nd day, consumption of food and water was common for the animals kept in the vivarium (from 3 to 8 mL daily per 100 g of body mass, and from 4.4 to 4.7 g of food daily per 100 g of body mass). One of 11 rats that were given DOX in DS2 (DexS-DOX conjugates) died at 12 days after drug administration. Autopsy of the dead rat revealed neither macroscopic changes in internal organs, nor defects of DOX administration.

Concentration of DOX in rat blood plasma after administration of various delivery systems

Figure 1. DOX concentrations in plasma after intraperitoneal administration to the rats: CaCO₃+DexS+DOX (1); free DOX (2); DexS+DOX (3)

In what follows, we describe the results of experiments involving healthy rats; free DOX and two types of DOX-containing delivery systems were injected intraperitoneally. Like as in the first experimental series, DOX was encapsulated in calcium carbonate cores doped with DexS and included in conjugates with this polyanion. During i.p. administration, the delivery systems enter intercellular fluid which is nearly similar to blood plasma. In our earlier works [14, 16], it has been demonstrated that vaterites were gradually destroyed in plasma, resulting into increased release rate of encapsulated compounds from porous carrier. Moreover, treatment of vaterites with DexS made it possible to reach prolonged release of DOX into blood plasma. Scanning electron microscopy demonstrated that structural changes in hybrid delivery systems occurring in plasma correlated with DOX release profiles [14]. After introduction of various delivery systems, DOX concentration in rat blood plasma was determined and compared with the concentration reached after administration of free DOX. Time profiles of DOX concentrations are seen in Fig. 1.

Before analysis of the obtained results, let us compare the literature data on DOX concentrations in blood of various tumor-bearing animals. It should be noted that the results obtained in experiments with rats cannot be directly used in pharmacology. The authors of [17] emphasize that it is necessary to estimate interspecies differences in distribution and elimination of drugs.

Free DOX is rapidly assimilated by organisms of DBA₂ mice. After intravenous introduction of 7 mg/kg of the drug, its concentration in plasma decreases by a factor of 100 within an hour (down to 0.2 nM/mL=116 ng/mL [10]). A 10-fold decrease in plasma DOX concentration (down to 1 µg/mL) was observed within 4 h, when almost similar amount of free DOX (5 mg/kg) was administered intravenously (i.v.) to tumor HeLa-bearing mice, [11]. Upon i.v. injection of DOX (10 mg/kg) to tumor MCF-7 bearing mice, the drug disappeared during 4 days. At 12 hrs, 70 ng/mL of DOX was found in plasma. Signs of cardiotoxicity (release of characteristic enzymes) were observed in 2 weeks after DOX administration [12]. The results of studies involving breast cancer patients treated with standard amounts of DOX showed that the concentrations of DOX in plasma ranged between 12 and 620 ng/mL. The risk of cardiomyopathy in such patients was under 4% [13]. Hence, DOX concentration in plasma after treatment may vary from 10 to 600 ng/mL. The total amount of drug in blood is directly proportional to animal size and, therefore, to blood volume.

One may assume that determination of DOX concentrations in rat blood plasma within the mentioned range, together with physical examination of animals, allows comparing effects of various DOX delivery systems after i.p. administration. Moreover, we should consider the fact that DOX is not only present in blood, but distributed in all organs of an animal.

Comparison of time profiles of DOX release from DexS-coated CaCO₃ cores and from DexS+DОХ conjugates into human blood plasma is discussed in [2]. In the case of conjugates, the DOX release profile (unlike that from doped carbonate cores) demonstrated burst release of the drug for the first 24 h. Later on, gradual increase in the released amount of drug (up to 70%) was observed for 2 weeks. As shown in Fig. 1, (curve 3) injection of the fast-releasing carriers is associated with higher DOX levels in the bloodstream.

The authors of [11] compared time profiles of DOX concentration in blood plasma of HeLa-bearing mice after i.v. administration of free DOX versus DOX incorporated into nanoparticles of various compositions. Similar results were obtained in the present work. High amounts of DOX were released from DS2 nanocarriers into plasma during the first hour after administration, unlike the case of free DOX injection (Fig. 1, curve 2). Increased plasma DOX concentration early after injection may be caused by release of DOX molecules that were weakly bound to the carriers. Similar situation is possible in the case of polymer-drug conjugates formation; despite equimolar ratio of components, complete attachment of DOX to DexS did not occur, due to considerable difference in sizes of molecules.

Calcium carbonate cores doped with DexS provided prolonged release of DOX with gradually increased concentration (Fig.1, curve 1). Note that DOX concentrations in plasma lie in the nanogram range typical of humans and animals treated with DOX.

Besides, the size range of the DOX delivery systems should be taken into account; they determine ability of the drug to penetrate into organs and tissues. Of course, nanosized conjugates have advantages over submicron-sized doped carbonate cores. Probably, this factor is responsible for increased concentration of released DOX by the end of second week after injection of the drug within polymer-drug conjugates.

Conclusions

Intraperitoneal administration of 2 mg of DOX in DS based on calcium carbonate cores doped with DexS in rats inoculated with Seidel hepatoma resulted in increase of life expectancy by 1.75 times and in decrease in ascites volume in laboratory animals. It is expected that increase in the dosage up to 4 mg per animal will lead to more efficient inhibition of tumor growth. This dose was used in the studies of dynamics of DOX release into blood plasma after i.p. administration of the drug to intact rats using delivery systems of various structures. In 2 days after introduction of free DOX to rats, the drug disappeared from blood plasma. Application of the delivery systems made it possible to prolong presence of the drug in blood. When similar amounts of DOX (4 mg per animal) were introduced by means of various delivery systems, DOX was present in blood plasma at different amounts, depending on the structure of a delivery system. Porous calcium carbonate cores doped with DexS allowed for release of DOX within 2 weeks at the rates under cardiotoxic concentrations. The release profile of DOX in blood plasma after injection of polymer-drug conjugate DexS-DOX had a complex pattern, due to the carrier structure. These DS release significantly higher amounts of DOX into plasma by 14^th day after beginning the experiment. Despite the difference in DOX release profiles, neither calcium carbonate, nor conjugate DS caused negative reactions in rats, as confirmed by observations of behavior and physical state of the animals, and autopsy results. Therefore, both studied drug delivery systems could be used for prolonged regional administration of antitumor DOX preparation.

Financial support

The study was performed within the framework of budget-supported research project №АААА-А20-120022090044-2, Institute of Macromolecular Compounds, RAS.

Conflict of interests

None declared.

References

Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev. 2004;56:185-229. doi: 10.1124/pr.56.2.6
Sudareva N, Suvorova O, Saprykina N, Vlasova E, Vilesov A. DOX delivery systems based on doped CaCO3 cores and polyanion-drug conjugates. J Microencapsul. 2021;38:164-176. doi: 10.1080/02652048.2021.1872724
Popryadukhin P, Sudareva N, Suvorova O, Yukina G, Sukhorukova E, Saprykina N, et al. Morphology of target drug delivery systems (CaCO3 vaterites covered with dextran sulfate) in rat muscular tissue. Cell Ther Transplant. 2020;9:78-84.
doi: 10.18620/ctt-1866-8836-2020-9-4-78-84
Sudareva N, Suvorova O, Saprykina N, Smirnova N, Bel'tiukov P, Petunov S, et al. Two-level delivery systems based on CaCO3 cores for oral administration of therapeutic peptides. J Microencapsul. 2018; 35:619-634. doi: 10.1080/02652048.2018.1559247
Youn Y, Bae H. Perspectives on the past, present, and future of cancer nanomedicine. Adv Drug Delivery Rev. 2018;130:3-11.
doi: 10.1016/j.addr.2018.05.008
Alven S, Nqoro X, Buyana B, Aderibigbe B. Polymer-drug conjugate, a potential therapeutic to combat breast and lung cancer. Pharmaceutics, 2020;12:406. doi: 10.3390/pharmaceutics12050406
Guidelines for the experimental (preclinical) study of new pharmacological substances. (Ed. Khabriev R). Medicine Publishers. 2005, 832 p (In Russian).
Revtovich M, Istomin U, Krasko O, Treshchalina E, Bichkovsky P, Yurkschtovich T, et al. Antitumor activity of the hydrogel form of cisplatin on Seidel ascitic hepatoma. Russ Biother J. 2016;15:96-101. (In Russian). doi: 10.17650/1726-9784-2016-15-4-96-101
Adiseshaiah P, Hall J, McNeil S. Nanomaterial standards for efficacy and toxicity assessment. WIREs Nanomed Nanobiotechnol. 2009;2:99,112. doi: 10.1002/wnan.66
Baurain R, Deprez-De Campeneere D, Trouet A. Determination of Daunorubicin, Doxorubicin and their fluorescent metabolites by high-pressure liquid chromatography: plasma levels in DBA2mice. Cancer Chemother Pharmacol. 1979;2:11-14.
Zhang C, Wu Y, Dong Y, Xu H, Zhao I. Quantification of DOX bioavailability in biological samples of mice by sensitive and precise HPLC assay. Pharm Biol. 2016; 54:55-61. doi: 10.3109/13880209.2015.1014918
Mondal L, Mukherjee B, Das K, Bhattacharya S, Dutta D, Chakraborty S, et al. CD-340 functionalized doxorubicin-loaded nanoparticle induces apoptosis and reduces tumor volume along with drug-related cardiotoxicity in mice. Int J Nanomed. 2019;14:8073-8094.
doi: 10.2147/IJN.S220740
Harahap Y, Ardiningsih P, Winarti A, Purwanto D. Analysis of the Doxorubicin and Doxorubicinol in the plasma of breast cancer patients for monitoring the toxicity of Doxorubicin. Drug Design Devel Ther. 2020;14:3469-3475. doi: 10.2147/DDDT.S251144
Sudareva N, Suvorova O, Saprykina N, Tomson V, Suslov D, Galibin O, Vilesov A. Morphology of hybrid doxorubicin delivery systems (dextran sulfate-coated CaCO3 vaterites) in human blood plasma. Cell Ther Transplant. 2021; 10:79-85.
doi: 10.18620/ctt-1866-8836-2021-10-1-79-85
Freireich E, Gehan E, Rall D, Schmidt L, Skipper H. Quantitative comparison of toxicity of anticancer agents in mouse, rat, hamster, dog, monkey and man. Cancer Chemother Res. 1966;50:219-224.
Sudareva N, Popryadukhin P, Saprykina N, Suvorova O, Yukina G, Galibin O, Vilesov A. CaCO3 vaterite as components of target drug delivery systems. Cell Ther Transplant. 2020;9:13-19. doi: 10.18620/ctt-1866-8836-2020-9-2-13-19
Li Y, Zhang C, Zhou S, He M, Zhang H, et al. Species difference in paclitaxel disposition correlated with poor pharmacological efficacy translation from mice to humans. Clin Pharm Adv Appl. 2018;10:165-174. doi: 10.2147/CPAA.S185449

" ["~DETAIL_TEXT"]=> string(31571) "

Introduction

Materials and methods

Reagents

Synthesis of carbonate cores

Doping of carbonate cores with DexS and DOX loading into delivery systems

Polymer-drug conjugates and their loading

In vivo experiments with rats

Transplantation of ascitic Seidel hepatoma (SH)

Introduction of DOX into rats

Determination of DOX content in plasma of rats

Results and discussion

First group of rats

The influence of DOX delivery systems based on porous calcium carbonate cores coated with DexS (CaCO₃+DexS) on development of Seidel hepatoma was studied in laboratory rats.

Second group of rats

Concentration of DOX in rat blood plasma after administration of various delivery systems

Figure 1. DOX concentrations in plasma after intraperitoneal administration to the rats: CaCO₃+DexS+DOX (1); free DOX (2); DexS+DOX (3)

Conclusions

Financial support

The study was performed within the framework of budget-supported research project №АААА-А20-120022090044-2, Institute of Macromolecular Compounds, RAS.

Conflict of interests

None declared.

References

Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev. 2004;56:185-229. doi: 10.1124/pr.56.2.6
Sudareva N, Suvorova O, Saprykina N, Vlasova E, Vilesov A. DOX delivery systems based on doped CaCO3 cores and polyanion-drug conjugates. J Microencapsul. 2021;38:164-176. doi: 10.1080/02652048.2021.1872724
Popryadukhin P, Sudareva N, Suvorova O, Yukina G, Sukhorukova E, Saprykina N, et al. Morphology of target drug delivery systems (CaCO3 vaterites covered with dextran sulfate) in rat muscular tissue. Cell Ther Transplant. 2020;9:78-84.
doi: 10.18620/ctt-1866-8836-2020-9-4-78-84
Sudareva N, Suvorova O, Saprykina N, Smirnova N, Bel'tiukov P, Petunov S, et al. Two-level delivery systems based on CaCO3 cores for oral administration of therapeutic peptides. J Microencapsul. 2018; 35:619-634. doi: 10.1080/02652048.2018.1559247
Youn Y, Bae H. Perspectives on the past, present, and future of cancer nanomedicine. Adv Drug Delivery Rev. 2018;130:3-11.
doi: 10.1016/j.addr.2018.05.008
Alven S, Nqoro X, Buyana B, Aderibigbe B. Polymer-drug conjugate, a potential therapeutic to combat breast and lung cancer. Pharmaceutics, 2020;12:406. doi: 10.3390/pharmaceutics12050406
Guidelines for the experimental (preclinical) study of new pharmacological substances. (Ed. Khabriev R). Medicine Publishers. 2005, 832 p (In Russian).
Revtovich M, Istomin U, Krasko O, Treshchalina E, Bichkovsky P, Yurkschtovich T, et al. Antitumor activity of the hydrogel form of cisplatin on Seidel ascitic hepatoma. Russ Biother J. 2016;15:96-101. (In Russian). doi: 10.17650/1726-9784-2016-15-4-96-101
Adiseshaiah P, Hall J, McNeil S. Nanomaterial standards for efficacy and toxicity assessment. WIREs Nanomed Nanobiotechnol. 2009;2:99,112. doi: 10.1002/wnan.66
Baurain R, Deprez-De Campeneere D, Trouet A. Determination of Daunorubicin, Doxorubicin and their fluorescent metabolites by high-pressure liquid chromatography: plasma levels in DBA2mice. Cancer Chemother Pharmacol. 1979;2:11-14.
Zhang C, Wu Y, Dong Y, Xu H, Zhao I. Quantification of DOX bioavailability in biological samples of mice by sensitive and precise HPLC assay. Pharm Biol. 2016; 54:55-61. doi: 10.3109/13880209.2015.1014918
Mondal L, Mukherjee B, Das K, Bhattacharya S, Dutta D, Chakraborty S, et al. CD-340 functionalized doxorubicin-loaded nanoparticle induces apoptosis and reduces tumor volume along with drug-related cardiotoxicity in mice. Int J Nanomed. 2019;14:8073-8094.
doi: 10.2147/IJN.S220740
Harahap Y, Ardiningsih P, Winarti A, Purwanto D. Analysis of the Doxorubicin and Doxorubicinol in the plasma of breast cancer patients for monitoring the toxicity of Doxorubicin. Drug Design Devel Ther. 2020;14:3469-3475. doi: 10.2147/DDDT.S251144
Sudareva N, Suvorova O, Saprykina N, Tomson V, Suslov D, Galibin O, Vilesov A. Morphology of hybrid doxorubicin delivery systems (dextran sulfate-coated CaCO3 vaterites) in human blood plasma. Cell Ther Transplant. 2021; 10:79-85.
doi: 10.18620/ctt-1866-8836-2021-10-1-79-85
Freireich E, Gehan E, Rall D, Schmidt L, Skipper H. Quantitative comparison of toxicity of anticancer agents in mouse, rat, hamster, dog, monkey and man. Cancer Chemother Res. 1966;50:219-224.
Sudareva N, Popryadukhin P, Saprykina N, Suvorova O, Yukina G, Galibin O, Vilesov A. CaCO3 vaterite as components of target drug delivery systems. Cell Ther Transplant. 2020;9:13-19. doi: 10.18620/ctt-1866-8836-2020-9-2-13-19
Li Y, Zhang C, Zhou S, He M, Zhang H, et al. Species difference in paclitaxel disposition correlated with poor pharmacological efficacy translation from mice to humans. Clin Pharm Adv Appl. 2018;10:165-174. doi: 10.2147/CPAA.S185449

" ["DETAIL_TEXT_TYPE"]=> string(4) "html" ["~DETAIL_TEXT_TYPE"]=> string(4) "html" ["PREVIEW_TEXT"]=> string(0) "" ["~PREVIEW_TEXT"]=> string(0) "" ["PREVIEW_TEXT_TYPE"]=> string(4) "text" ["~PREVIEW_TEXT_TYPE"]=> string(4) "text" ["PREVIEW_PICTURE"]=> NULL ["~PREVIEW_PICTURE"]=> NULL ["LANG_DIR"]=> string(4) "/ru/" ["~LANG_DIR"]=> string(4) "/ru/" ["SORT"]=> string(2) "20" ["~SORT"]=> string(2) "20" ["CODE"]=> string(100) "saso3-vaterity-pokrytye-dekstransulfatom-kak-sistemy-dlya-regionarnogo-vvedeniya-doksorubitsina-krys" ["~CODE"]=> string(100) "saso3-vaterity-pokrytye-dekstransulfatom-kak-sistemy-dlya-regionarnogo-vvedeniya-doksorubitsina-krys" ["EXTERNAL_ID"]=> string(4) "2047" ["~EXTERNAL_ID"]=> string(4) "2047" ["IBLOCK_TYPE_ID"]=> string(7) "journal" ["~IBLOCK_TYPE_ID"]=> string(7) "journal" ["IBLOCK_CODE"]=> string(7) "volumes" ["~IBLOCK_CODE"]=> string(7) "volumes" ["IBLOCK_EXTERNAL_ID"]=> string(1) "2" ["~IBLOCK_EXTERNAL_ID"]=> string(1) "2" ["LID"]=> string(2) "s2" ["~LID"]=> string(2) "s2" ["EDIT_LINK"]=> NULL ["DELETE_LINK"]=> NULL ["DISPLAY_ACTIVE_FROM"]=> string(0) "" ["IPROPERTY_VALUES"]=> array(18) { ["ELEMENT_META_TITLE"]=> string(191) "СаСО3 ватериты, покрытые декстрансульфатом, как системы для регионарного введения доксорубицина крысам" ["ELEMENT_META_KEYWORDS"]=> string(0) "" ["ELEMENT_META_DESCRIPTION"]=> string(295) "СаСО3 ватериты, покрытые декстрансульфатом, как системы для регионарного введения доксорубицина крысамDextran sulfate coated CaCO3 vaterites as the systems for regional administration of doxorubicin to rats" ["ELEMENT_PREVIEW_PICTURE_FILE_ALT"]=> string(3344) "Доксорубицин (ДОХ) – водорастворимый антрациклиновый антибиотик, обладающий высокой противораковой эффективностью. Можно добиться уменьшения концентрации ДОХ в крови ниже кардиотоксического уровня в процессе терапии, формируя депо, содержащее системы доставки ДОХ с пролонгированным высвобождением лекарства. Для этих целей использовали кальций карбонатные пористые ватериты, допированные полианионом декстран сульфатом. Субмикронные размеры носителей не позволяют свободно включаться им в кровеносное русло. Распространяется токсическое лекарство по организму только после попадания в кровь в результате высвобождения из систем доставки. Внутрибрюшинное введение крысам с перевитой гепатомой Зайделя ДОХ-содержащих систем доставки позволило оценить эффективную концентрацию ДОХ, тормозящую рост опухоли и уменьшающую объем асцитной жидкости. Динамику поступления ДОХ в кровь здоровых крыс после внутрибрюшинного введения 4 мг ДОХ в системах доставки различной природы определяли методом ВЭЖХ. Введенное при помощи допированных декстрансульфатом субмикронных карбонатных ядер лекарство высвобождается в кровь крыс в течение двух недель в концентрациях, меньших токсичных значений. При использовании в качестве системы доставки наноразмерного конъюгата декстрансульфат+ДОХ в крови крыс обнаруживается лекарство в значительно больших концентрациях. Независимо от концентрации ДОХ в плазме результаты физикального осмотра, а также аутопсии крыс в течение 21 дня после внутрибрюшинного введения ДОХ в разных системах доставки, свидетельствуют об отсутствии негативных реакций у животных. <h2>Ключевые слова</h2> Доксорубицин, система доставки лекарства, СаСО3, декстрансульфат, конъюгат полимер-лекарство, плазма крови." ["ELEMENT_PREVIEW_PICTURE_FILE_TITLE"]=> string(191) "СаСО3 ватериты, покрытые декстрансульфатом, как системы для регионарного введения доксорубицина крысам" ["ELEMENT_DETAIL_PICTURE_FILE_ALT"]=> string(191) "СаСО3 ватериты, покрытые декстрансульфатом, как системы для регионарного введения доксорубицина крысам" ["ELEMENT_DETAIL_PICTURE_FILE_TITLE"]=> string(191) "СаСО3 ватериты, покрытые декстрансульфатом, как системы для регионарного введения доксорубицина крысам" ["SECTION_META_TITLE"]=> string(191) "СаСО3 ватериты, покрытые декстрансульфатом, как системы для регионарного введения доксорубицина крысам" ["SECTION_META_KEYWORDS"]=> string(191) "СаСО3 ватериты, покрытые декстрансульфатом, как системы для регионарного введения доксорубицина крысам" ["SECTION_META_DESCRIPTION"]=> string(191) "СаСО3 ватериты, покрытые декстрансульфатом, как системы для регионарного введения доксорубицина крысам" ["SECTION_PICTURE_FILE_ALT"]=> string(191) "СаСО3 ватериты, покрытые декстрансульфатом, как системы для регионарного введения доксорубицина крысам" ["SECTION_PICTURE_FILE_TITLE"]=> string(191) "СаСО3 ватериты, покрытые декстрансульфатом, как системы для регионарного введения доксорубицина крысам" ["SECTION_PICTURE_FILE_NAME"]=> string(100) "saso3-vaterity-pokrytye-dekstransulfatom-kak-sistemy-dlya-regionarnogo-vvedeniya-doksorubitsina-krys" ["SECTION_DETAIL_PICTURE_FILE_ALT"]=> string(191) "СаСО3 ватериты, покрытые декстрансульфатом, как системы для регионарного введения доксорубицина крысам" ["SECTION_DETAIL_PICTURE_FILE_TITLE"]=> string(191) "СаСО3 ватериты, покрытые декстрансульфатом, как системы для регионарного введения доксорубицина крысам" ["SECTION_DETAIL_PICTURE_FILE_NAME"]=> string(100) "saso3-vaterity-pokrytye-dekstransulfatom-kak-sistemy-dlya-regionarnogo-vvedeniya-doksorubitsina-krys" ["ELEMENT_PREVIEW_PICTURE_FILE_NAME"]=> string(100) "saso3-vaterity-pokrytye-dekstransulfatom-kak-sistemy-dlya-regionarnogo-vvedeniya-doksorubitsina-krys" ["ELEMENT_DETAIL_PICTURE_FILE_NAME"]=> string(100) "saso3-vaterity-pokrytye-dekstransulfatom-kak-sistemy-dlya-regionarnogo-vvedeniya-doksorubitsina-krys" } ["FIELDS"]=> array(1) { ["IBLOCK_SECTION_ID"]=> string(3) "203" } ["PROPERTIES"]=> array(18) { ["KEYWORDS"]=> array(36) { ["ID"]=> string(2) "19" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:46:01" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(27) "Ключевые слова" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(8) "KEYWORDS" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "Y" ["XML_ID"]=> string(2) "19" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "4" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "Y" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "Y" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> bool(false) ["VALUE"]=> bool(false) ["DESCRIPTION"]=> bool(false) ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> bool(false) ["~DESCRIPTION"]=> bool(false) ["~NAME"]=> string(27) "Ключевые слова" ["~DEFAULT_VALUE"]=> string(0) "" } ["SUBMITTED"]=> array(36) { ["ID"]=> string(2) "20" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(21) "Дата подачи" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "SUBMITTED" ["DEFAULT_VALUE"]=> NULL ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "20" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> NULL ["VALUE"]=> string(0) "" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(0) "" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(21) "Дата подачи" ["~DEFAULT_VALUE"]=> NULL } ["ACCEPTED"]=> array(36) { ["ID"]=> string(2) "21" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(25) "Дата принятия" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(8) "ACCEPTED" ["DEFAULT_VALUE"]=> NULL ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "21" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> NULL ["VALUE"]=> string(0) "" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(0) "" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(25) "Дата принятия" ["~DEFAULT_VALUE"]=> NULL } ["PUBLISHED"]=> array(36) { ["ID"]=> string(2) "22" ["TIMESTAMP_X"]=> string(19) "2015-09-02 17:21:42" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(29) "Дата публикации" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "PUBLISHED" ["DEFAULT_VALUE"]=> NULL ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "22" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(8) "DateTime" ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> NULL ["VALUE"]=> string(0) "" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(0) "" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(29) "Дата публикации" ["~DEFAULT_VALUE"]=> NULL } ["CONTACT"]=> array(36) { ["ID"]=> string(2) "23" ["TIMESTAMP_X"]=> string(19) "2015-09-03 14:43:05" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(14) "Контакт" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "CONTACT" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "23" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "3" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "N" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> NULL ["VALUE"]=> string(0) "" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(0) "" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(14) "Контакт" ["~DEFAULT_VALUE"]=> string(0) "" } ["AUTHORS"]=> array(36) { ["ID"]=> string(2) "24" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:45:07" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Авторы" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "AUTHORS" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "E" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "Y" ["XML_ID"]=> string(2) "24" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "3" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(13) "EAutocomplete" ["USER_TYPE_SETTINGS"]=> array(9) { ["VIEW"]=> string(1) "E" ["SHOW_ADD"]=> string(1) "Y" ["MAX_WIDTH"]=> int(0) ["MIN_HEIGHT"]=> int(24) ["MAX_HEIGHT"]=> int(1000) ["BAN_SYM"]=> string(2) ",;" ["REP_SYM"]=> string(1) " " ["OTHER_REP_SYM"]=> string(0) "" ["IBLOCK_MESS"]=> string(1) "N" } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> bool(false) ["VALUE"]=> bool(false) ["DESCRIPTION"]=> bool(false) ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> bool(false) ["~DESCRIPTION"]=> bool(false) ["~NAME"]=> string(12) "Авторы" ["~DEFAULT_VALUE"]=> string(0) "" } ["AUTHOR_RU"]=> array(36) { ["ID"]=> string(2) "25" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Авторы" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "AUTHOR_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "25" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28475" ["VALUE"]=> array(2) { ["TEXT"]=> string(313) "Наталья Н. Сударева1,2, Ольга М. Суворова1, Дмитрий Н. Суслов3, Олег В. Галибин2, Александр Д. Вилесов1,2 " ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(241) "

Наталья Н. Сударева^1,2, Ольга М. Суворова¹, Дмитрий Н. Суслов³, Олег В. Галибин², Александр Д. Вилесов^1,2

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Авторы" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["ORGANIZATION_RU"]=> array(36) { ["ID"]=> string(2) "26" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(22) "Организации" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "26" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28476" ["VALUE"]=> array(2) { ["TEXT"]=> string(660) "1 Институт высокомолекулярных соединений РАН, Санкт-Петербург, Россия 2 Первый Санкт-Петербургский государственный медицинский университет им. акад. И. П. Павлова, Санкт-Петербург, Россия 3 Российский научный центр радиологии и хирургических технологий им. акад. А.М. Гранова, Санкт-Петербург, Россия" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(600) "

¹ Институт высокомолекулярных соединений РАН, Санкт-Петербург, Россия
² Первый Санкт-Петербургский государственный медицинский университет им. акад. И. П. Павлова, Санкт-Петербург, Россия
³ Российский научный центр радиологии и хирургических технологий им. акад. А.М. Гранова, Санкт-Петербург, Россия

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(22) "Организации" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["SUMMARY_RU"]=> array(36) { ["ID"]=> string(2) "27" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(29) "Описание/Резюме" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "27" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28477" ["VALUE"]=> array(2) { ["TEXT"]=> string(3344) "Доксорубицин (ДОХ) – водорастворимый антрациклиновый антибиотик, обладающий высокой противораковой эффективностью. Можно добиться уменьшения концентрации ДОХ в крови ниже кардиотоксического уровня в процессе терапии, формируя депо, содержащее системы доставки ДОХ с пролонгированным высвобождением лекарства. Для этих целей использовали кальций карбонатные пористые ватериты, допированные полианионом декстран сульфатом. Субмикронные размеры носителей не позволяют свободно включаться им в кровеносное русло. Распространяется токсическое лекарство по организму только после попадания в кровь в результате высвобождения из систем доставки. Внутрибрюшинное введение крысам с перевитой гепатомой Зайделя ДОХ-содержащих систем доставки позволило оценить эффективную концентрацию ДОХ, тормозящую рост опухоли и уменьшающую объем асцитной жидкости. Динамику поступления ДОХ в кровь здоровых крыс после внутрибрюшинного введения 4 мг ДОХ в системах доставки различной природы определяли методом ВЭЖХ. Введенное при помощи допированных декстрансульфатом субмикронных карбонатных ядер лекарство высвобождается в кровь крыс в течение двух недель в концентрациях, меньших токсичных значений. При использовании в качестве системы доставки наноразмерного конъюгата декстрансульфат+ДОХ в крови крыс обнаруживается лекарство в значительно больших концентрациях. Независимо от концентрации ДОХ в плазме результаты физикального осмотра, а также аутопсии крыс в течение 21 дня после внутрибрюшинного введения ДОХ в разных системах доставки, свидетельствуют об отсутствии негативных реакций у животных. <h2>Ключевые слова</h2> Доксорубицин, система доставки лекарства, СаСО3, декстрансульфат, конъюгат полимер-лекарство, плазма крови." ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(3276) "

Доксорубицин (ДОХ) – водорастворимый антрациклиновый антибиотик, обладающий высокой противораковой эффективностью. Можно добиться уменьшения концентрации ДОХ в крови ниже кардиотоксического уровня в процессе терапии, формируя депо, содержащее системы доставки ДОХ с пролонгированным высвобождением лекарства. Для этих целей использовали кальций карбонатные пористые ватериты, допированные полианионом декстран сульфатом. Субмикронные размеры носителей не позволяют свободно включаться им в кровеносное русло. Распространяется токсическое лекарство по организму только после попадания в кровь в результате высвобождения из систем доставки. Внутрибрюшинное введение крысам с перевитой гепатомой Зайделя ДОХ-содержащих систем доставки позволило оценить эффективную концентрацию ДОХ, тормозящую рост опухоли и уменьшающую объем асцитной жидкости. Динамику поступления ДОХ в кровь здоровых крыс после внутрибрюшинного введения 4 мг ДОХ в системах доставки различной природы определяли методом ВЭЖХ. Введенное при помощи допированных декстрансульфатом субмикронных карбонатных ядер лекарство высвобождается в кровь крыс в течение двух недель в концентрациях, меньших токсичных значений. При использовании в качестве системы доставки наноразмерного конъюгата декстрансульфат+ДОХ в крови крыс обнаруживается лекарство в значительно больших концентрациях. Независимо от концентрации ДОХ в плазме результаты физикального осмотра, а также аутопсии крыс в течение 21 дня после внутрибрюшинного введения ДОХ в разных системах доставки, свидетельствуют об отсутствии негативных реакций у животных.

Ключевые слова

Доксорубицин, система доставки лекарства, СаСО₃, декстрансульфат, конъюгат полимер-лекарство, плазма крови.

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(29) "Описание/Резюме" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["DOI"]=> array(36) { ["ID"]=> string(2) "28" ["TIMESTAMP_X"]=> string(19) "2016-04-06 14:11:12" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(3) "DOI" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(3) "DOI" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "28" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28478" ["VALUE"]=> string(40) "10.18620/ctt-1866-8836-2021-10-3-4-71-77" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(40) "10.18620/ctt-1866-8836-2021-10-3-4-71-77" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(3) "DOI" ["~DEFAULT_VALUE"]=> string(0) "" } ["AUTHOR_EN"]=> array(36) { ["ID"]=> string(2) "37" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(6) "Author" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "AUTHOR_EN" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "37" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28479" ["VALUE"]=> array(2) { ["TEXT"]=> string(243) " Natalia N. Sudareva1,2, Olga М. Suvorova1, Dmitry N. Suslov3, Oleg V. Galibin2, Aleksandr D. Vilesov1,2 " ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(171) "

Natalia N. Sudareva^1,2, Olga М. Suvorova¹, Dmitry N. Suslov³, Oleg V. Galibin², Aleksandr D. Vilesov^1,2

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(6) "Author" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["ORGANIZATION_EN"]=> array(36) { ["ID"]=> string(2) "38" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Organization" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_EN" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "38" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28480" ["VALUE"]=> array(2) { ["TEXT"]=> string(793) "1 Institute of Macromolecular Compounds RAS, St. Petersburg, Russia 2 Pavlov University, St. Petersburg, Russia 3 Granov Russian Research Center of Radiology and Surgical Technologies, St. Petersburg, Russia Correspondence: Dr. Natalia N. Sudareva, Institute of Macromolecular Compounds RAS, St. Petersburg, Russia E-mail: nnsas@mail.ru Citation: Sudareva NN, Suvorova OM, Suslov DN et al. Dextran sulfate coated CaCO3 vaterites as the systems for regional administration of doxorubicin to rats. Cell Ther Transplant 2021; 10(3-4): 71-77." ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(649) "

¹ Institute of Macromolecular Compounds RAS, St. Petersburg, Russia
² Pavlov University, St. Petersburg, Russia
³ Granov Russian Research Center of Radiology and Surgical Technologies, St. Petersburg, Russia

Correspondence:
Dr. Natalia N. Sudareva, Institute of Macromolecular Compounds RAS, St. Petersburg, Russia
E-mail: nnsas@mail.ru

Citation: Sudareva NN, Suvorova OM, Suslov DN et al. Dextran sulfate coated CaCO₃ vaterites as the systems for regional administration of doxorubicin to rats. Cell Ther Transplant 2021; 10(3-4): 71-77.

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(12) "Organization" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["SUMMARY_EN"]=> array(36) { ["ID"]=> string(2) "39" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(21) "Description / Summary" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_EN" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "39" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28481" ["VALUE"]=> array(2) { ["TEXT"]=> string(1842) "Doxorubicin (DOX) is a water-soluble anthracycline antibiotic possessing high anti-cancer activity. It is possible to achieve decrease in DOX concentration in blood (below the cardiotoxic level) during therapy by forming a depot containing DOX delivery systems that provide prolonged release of the drug. To this purpose, porous calcium carbonate particles (vaterites) coated with polyanion (dextran sulfate) were used. Due to submicron sizes of carriers, they do not freely enter bloodstream. The toxic drug is distributed in the organism only after entering the blood due to release from the delivery systems. Upon intraperitoneal administration of the DOX-containing delivery systems to rats inoculated with Seidel hepatoma, an efficient DOX concentration has been achieved which inhibited tumor growth and reduced the amount of ascitic fluid. Time profiles of DOX release into bloodstream of healthy rats were studied by HPLC after intraperitoneal administration of 4 mg of DOX, using various delivery systems. The drug injected in the form of dextran sulfate coated submicron carbonate cores was released within two weeks, and its concentrations were under the toxicity levels. When the nano-sized DexS+DOX conjugate was used for the drug delivery, DOX was found in rat blood at significantly higher concentrations. Irrespective of drug concentration in plasma, the results of physical examination and autopsy of rats performed on day 21 after intraperitoneal administration of DOX by various delivery systems indicated the absence of any negative reactions in animals. <h2>Keywords</h2> Doxorubicin, drug delivery system, CaCO3, dextran sulfate, polymer-drug conjugate, blood plasma." ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(1774) "

Doxorubicin (DOX) is a water-soluble anthracycline antibiotic possessing high anti-cancer activity. It is possible to achieve decrease in DOX concentration in blood (below the cardiotoxic level) during therapy by forming a depot containing DOX delivery systems that provide prolonged release of the drug. To this purpose, porous calcium carbonate particles (vaterites) coated with polyanion (dextran sulfate) were used. Due to submicron sizes of carriers, they do not freely enter bloodstream. The toxic drug is distributed in the organism only after entering the blood due to release from the delivery systems. Upon intraperitoneal administration of the DOX-containing delivery systems to rats inoculated with Seidel hepatoma, an efficient DOX concentration has been achieved which inhibited tumor growth and reduced the amount of ascitic fluid. Time profiles of DOX release into bloodstream of healthy rats were studied by HPLC after intraperitoneal administration of 4 mg of DOX, using various delivery systems. The drug injected in the form of dextran sulfate coated submicron carbonate cores was released within two weeks, and its concentrations were under the toxicity levels. When the nano-sized DexS+DOX conjugate was used for the drug delivery, DOX was found in rat blood at significantly higher concentrations. Irrespective of drug concentration in plasma, the results of physical examination and autopsy of rats performed on day 21 after intraperitoneal administration of DOX by various delivery systems indicated the absence of any negative reactions in animals.

Keywords

Doxorubicin, drug delivery system, CaCO₃, dextran sulfate, polymer-drug conjugate, blood plasma.

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(21) "Description / Summary" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["NAME_EN"]=> array(36) { ["ID"]=> string(2) "40" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:49:47" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(4) "Name" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "NAME_EN" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "40" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28482" ["VALUE"]=> string(104) "Dextran sulfate coated CaCO3 vaterites as the systems for regional administration of doxorubicin to rats" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(104) "Dextran sulfate coated CaCO3 vaterites as the systems for regional administration of doxorubicin to rats" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(4) "Name" ["~DEFAULT_VALUE"]=> string(0) "" } ["FULL_TEXT_RU"]=> array(36) { ["ID"]=> string(2) "42" ["TIMESTAMP_X"]=> string(19) "2015-09-07 20:29:18" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(23) "Полный текст" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(12) "FULL_TEXT_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "42" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> NULL ["VALUE"]=> string(0) "" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(0) "" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(23) "Полный текст" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["PDF_RU"]=> array(36) { ["ID"]=> string(2) "43" ["TIMESTAMP_X"]=> string(19) "2015-09-09 16:05:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(7) "PDF RUS" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(6) "PDF_RU" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "F" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "43" ["FILE_TYPE"]=> string(18) "doc, txt, rtf, pdf" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28483" ["VALUE"]=> string(4) "2745" ["DESCRIPTION"]=> NULL ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(4) "2745" ["~DESCRIPTION"]=> NULL ["~NAME"]=> string(7) "PDF RUS" ["~DEFAULT_VALUE"]=> string(0) "" } ["PDF_EN"]=> array(36) { ["ID"]=> string(2) "44" ["TIMESTAMP_X"]=> string(19) "2015-09-09 16:05:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(7) "PDF ENG" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(6) "PDF_EN" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "F" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "44" ["FILE_TYPE"]=> string(18) "doc, txt, rtf, pdf" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28484" ["VALUE"]=> string(4) "2746" ["DESCRIPTION"]=> NULL ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(4) "2746" ["~DESCRIPTION"]=> NULL ["~NAME"]=> string(7) "PDF ENG" ["~DEFAULT_VALUE"]=> string(0) "" } ["NAME_LONG"]=> array(36) { ["ID"]=> string(2) "45" ["TIMESTAMP_X"]=> string(19) "2023-04-13 00:55:00" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(72) "Название (для очень длинных заголовков)" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "NAME_LONG" ["DEFAULT_VALUE"]=> array(2) { ["TYPE"]=> string(4) "HTML" ["TEXT"]=> string(0) "" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "45" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(80) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> NULL ["VALUE"]=> string(0) "" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(0) "" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(72) "Название (для очень длинных заголовков)" ["~DEFAULT_VALUE"]=> array(2) { ["TYPE"]=> string(4) "HTML" ["TEXT"]=> string(0) "" } } } ["DISPLAY_PROPERTIES"]=> array(8) { ["AUTHOR_EN"]=> array(37) { ["ID"]=> string(2) "37" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(6) "Author" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "AUTHOR_EN" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "37" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28479" ["VALUE"]=> array(2) { ["TEXT"]=> string(243) " Natalia N. Sudareva1,2, Olga М. Suvorova1, Dmitry N. Suslov3, Oleg V. Galibin2, Aleksandr D. Vilesov1,2 " ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(171) "

Natalia N. Sudareva^1,2, Olga М. Suvorova¹, Dmitry N. Suslov³, Oleg V. Galibin², Aleksandr D. Vilesov^1,2

" } ["SUMMARY_EN"]=> array(37) { ["ID"]=> string(2) "39" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(21) "Description / Summary" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_EN" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "39" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28481" ["VALUE"]=> array(2) { ["TEXT"]=> string(1842) "Doxorubicin (DOX) is a water-soluble anthracycline antibiotic possessing high anti-cancer activity. It is possible to achieve decrease in DOX concentration in blood (below the cardiotoxic level) during therapy by forming a depot containing DOX delivery systems that provide prolonged release of the drug. To this purpose, porous calcium carbonate particles (vaterites) coated with polyanion (dextran sulfate) were used. Due to submicron sizes of carriers, they do not freely enter bloodstream. The toxic drug is distributed in the organism only after entering the blood due to release from the delivery systems. Upon intraperitoneal administration of the DOX-containing delivery systems to rats inoculated with Seidel hepatoma, an efficient DOX concentration has been achieved which inhibited tumor growth and reduced the amount of ascitic fluid. Time profiles of DOX release into bloodstream of healthy rats were studied by HPLC after intraperitoneal administration of 4 mg of DOX, using various delivery systems. The drug injected in the form of dextran sulfate coated submicron carbonate cores was released within two weeks, and its concentrations were under the toxicity levels. When the nano-sized DexS+DOX conjugate was used for the drug delivery, DOX was found in rat blood at significantly higher concentrations. Irrespective of drug concentration in plasma, the results of physical examination and autopsy of rats performed on day 21 after intraperitoneal administration of DOX by various delivery systems indicated the absence of any negative reactions in animals. <h2>Keywords</h2> Doxorubicin, drug delivery system, CaCO3, dextran sulfate, polymer-drug conjugate, blood plasma." ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(1774) "

Keywords

Doxorubicin, drug delivery system, CaCO₃, dextran sulfate, polymer-drug conjugate, blood plasma.

Keywords

Doxorubicin, drug delivery system, CaCO₃, dextran sulfate, polymer-drug conjugate, blood plasma.

" } ["DOI"]=> array(37) { ["ID"]=> string(2) "28" ["TIMESTAMP_X"]=> string(19) "2016-04-06 14:11:12" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(3) "DOI" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(3) "DOI" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "28" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28478" ["VALUE"]=> string(40) "10.18620/ctt-1866-8836-2021-10-3-4-71-77" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(40) "10.18620/ctt-1866-8836-2021-10-3-4-71-77" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(3) "DOI" ["~DEFAULT_VALUE"]=> string(0) "" ["DISPLAY_VALUE"]=> string(40) "10.18620/ctt-1866-8836-2021-10-3-4-71-77" } ["NAME_EN"]=> array(37) { ["ID"]=> string(2) "40" ["TIMESTAMP_X"]=> string(19) "2015-09-03 10:49:47" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(4) "Name" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(7) "NAME_EN" ["DEFAULT_VALUE"]=> string(0) "" ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "80" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "40" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "Y" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> NULL ["USER_TYPE_SETTINGS"]=> NULL ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28482" ["VALUE"]=> string(104) "Dextran sulfate coated CaCO3 vaterites as the systems for regional administration of doxorubicin to rats" ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> string(104) "Dextran sulfate coated CaCO3 vaterites as the systems for regional administration of doxorubicin to rats" ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(4) "Name" ["~DEFAULT_VALUE"]=> string(0) "" ["DISPLAY_VALUE"]=> string(104) "Dextran sulfate coated CaCO3 vaterites as the systems for regional administration of doxorubicin to rats" } ["ORGANIZATION_EN"]=> array(37) { ["ID"]=> string(2) "38" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Organization" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_EN" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "38" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28480" ["VALUE"]=> array(2) { ["TEXT"]=> string(793) "1 Institute of Macromolecular Compounds RAS, St. Petersburg, Russia 2 Pavlov University, St. Petersburg, Russia 3 Granov Russian Research Center of Radiology and Surgical Technologies, St. Petersburg, Russia Correspondence: Dr. Natalia N. Sudareva, Institute of Macromolecular Compounds RAS, St. Petersburg, Russia E-mail: nnsas@mail.ru Citation: Sudareva NN, Suvorova OM, Suslov DN et al. Dextran sulfate coated CaCO3 vaterites as the systems for regional administration of doxorubicin to rats. Cell Ther Transplant 2021; 10(3-4): 71-77." ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(649) "

Correspondence:
Dr. Natalia N. Sudareva, Institute of Macromolecular Compounds RAS, St. Petersburg, Russia
E-mail: nnsas@mail.ru

" } ["AUTHOR_RU"]=> array(37) { ["ID"]=> string(2) "25" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(12) "Авторы" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(9) "AUTHOR_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "25" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28475" ["VALUE"]=> array(2) { ["TEXT"]=> string(313) "Наталья Н. Сударева1,2, Ольга М. Суворова1, Дмитрий Н. Суслов3, Олег В. Галибин2, Александр Д. Вилесов1,2 " ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(241) "

Наталья Н. Сударева^1,2, Ольга М. Суворова¹, Дмитрий Н. Суслов³, Олег В. Галибин², Александр Д. Вилесов^1,2

" } ["SUMMARY_RU"]=> array(37) { ["ID"]=> string(2) "27" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(29) "Описание/Резюме" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "27" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28477" ["VALUE"]=> array(2) { ["TEXT"]=> string(3344) "Доксорубицин (ДОХ) – водорастворимый антрациклиновый антибиотик, обладающий высокой противораковой эффективностью. Можно добиться уменьшения концентрации ДОХ в крови ниже кардиотоксического уровня в процессе терапии, формируя депо, содержащее системы доставки ДОХ с пролонгированным высвобождением лекарства. Для этих целей использовали кальций карбонатные пористые ватериты, допированные полианионом декстран сульфатом. Субмикронные размеры носителей не позволяют свободно включаться им в кровеносное русло. Распространяется токсическое лекарство по организму только после попадания в кровь в результате высвобождения из систем доставки. Внутрибрюшинное введение крысам с перевитой гепатомой Зайделя ДОХ-содержащих систем доставки позволило оценить эффективную концентрацию ДОХ, тормозящую рост опухоли и уменьшающую объем асцитной жидкости. Динамику поступления ДОХ в кровь здоровых крыс после внутрибрюшинного введения 4 мг ДОХ в системах доставки различной природы определяли методом ВЭЖХ. Введенное при помощи допированных декстрансульфатом субмикронных карбонатных ядер лекарство высвобождается в кровь крыс в течение двух недель в концентрациях, меньших токсичных значений. При использовании в качестве системы доставки наноразмерного конъюгата декстрансульфат+ДОХ в крови крыс обнаруживается лекарство в значительно больших концентрациях. Независимо от концентрации ДОХ в плазме результаты физикального осмотра, а также аутопсии крыс в течение 21 дня после внутрибрюшинного введения ДОХ в разных системах доставки, свидетельствуют об отсутствии негативных реакций у животных. <h2>Ключевые слова</h2> Доксорубицин, система доставки лекарства, СаСО3, декстрансульфат, конъюгат полимер-лекарство, плазма крови." ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(3276) "

Ключевые слова

Доксорубицин, система доставки лекарства, СаСО₃, декстрансульфат, конъюгат полимер-лекарство, плазма крови.

Ключевые слова

Доксорубицин, система доставки лекарства, СаСО₃, декстрансульфат, конъюгат полимер-лекарство, плазма крови.

" } ["ORGANIZATION_RU"]=> array(37) { ["ID"]=> string(2) "26" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(22) "Организации" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(15) "ORGANIZATION_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "26" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "28476" ["VALUE"]=> array(2) { ["TEXT"]=> string(660) "1 Институт высокомолекулярных соединений РАН, Санкт-Петербург, Россия 2 Первый Санкт-Петербургский государственный медицинский университет им. акад. И. П. Павлова, Санкт-Петербург, Россия 3 Российский научный центр радиологии и хирургических технологий им. акад. А.М. Гранова, Санкт-Петербург, Россия" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(600) "

" } } } [2]=> array(49) { ["IBLOCK_SECTION_ID"]=> string(3) "203" ["~IBLOCK_SECTION_ID"]=> string(3) "203" ["ID"]=> string(4) "2046" ["~ID"]=> string(4) "2046" ["IBLOCK_ID"]=> string(1) "2" ["~IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(182) "Оптимизированный протокол выделения и культивирования мышиных мезенхимальных стромальных клеток" ["~NAME"]=> string(182) "Оптимизированный протокол выделения и культивирования мышиных мезенхимальных стромальных клеток" ["ACTIVE_FROM"]=> NULL ["~ACTIVE_FROM"]=> NULL ["TIMESTAMP_X"]=> string(22) "01/26/2022 11:21:46 am" ["~TIMESTAMP_X"]=> string(22) "01/26/2022 11:21:46 am" ["DETAIL_PAGE_URL"]=> string(160) "/en/archive/tom-10-nomer-3-4/eksperimentalnye-issledovaniya/optimizirovannyy-protokol-vydeleniya-i-kultivirovaniya-myshinykh-mezenkhimalnykh-stromalnykh-kletok/" ["~DETAIL_PAGE_URL"]=> string(160) "/en/archive/tom-10-nomer-3-4/eksperimentalnye-issledovaniya/optimizirovannyy-protokol-vydeleniya-i-kultivirovaniya-myshinykh-mezenkhimalnykh-stromalnykh-kletok/" ["LIST_PAGE_URL"]=> string(12) "/en/archive/" ["~LIST_PAGE_URL"]=> string(12) "/en/archive/" ["DETAIL_TEXT"]=> string(38539) "

Introduction

Bone marrow (BM) stroma is a complex tissue containing several cell types which provide a microenvironment for hematopoiesis and contribute to the maintenance and regeneration of skeletal tissues [1]. Two major stem cell populations with distinct progenies are found within adult BM, i.e., hematopoietic stem cells and mesenchymal stem cells (MSCs) [2]. MSCs were first described by Friedenstein et al. Who found that MSCs can be isolated by physical adhere to culture plates, able to form colonies with cells have fibroblast shape in vitro [3]. MSCs have also been defined as colony-forming fibroblastic cells, marrow stromal stem cells, mesenchymal progenitor cells [4], and, even, medicinal signaling cells [5].

MSCs are of interest in clinical applications for their ability to modulate the immune system, as well as their potential to regenerate tissues [6]. Medical applications of MSC require in vitro expansion in order to obtain sufficient cell numbers to achieve therapeutic results. Therefore, determination of optimal culture conditions is a prerequisite for usage of MSC in clinical setting [7].

However, prior to clinical implementation, the animal models are needed to confirm their efficacy and safety [8]. MSCs from mouse bone marrow (BM) provide valuable information on cell biology, potential function [9] and biochemical characteristics of MSC populations [8]. Human and rat bone marrow mesenchymal stem cells have been the most extensively characterized, due to relatively easy isolation procedure, their adherence to plastic dishes, and extensive in vitro expansion [10].

Isolation and purification of BM-MSCs from mouse are more difficult than from other species [9]. This observation is due to low frequency of BM-MSCs [11] and high proportion of hematopoietic stem cells (HSCs) in bone marrow [9]. The stromal cells exist near the surface of the bone, thus making it difficult to obtain enough MSCs, even after flushing BM by the cell preparation [8]. In addition, lack of specific mouse BM-MSC markers increases the difficulties [9].

To date, several suggestions were presented to improve the method of mouse BM-MSCs isolation, propagation, and culture, but none of them are widely acceptable [12]. We have reviewed most of the available protocols published so far, and attempted to develop an optimized, efficient, uncomplicated protocol suitable for production of a large number of MSC(M) in less than a week, thus enabling their use in regenerative medicine.

In this paper, we describe our MSC(M) isolation protocol in details, with appropriate illustrations, and index of some technical problems that occur when isolating and culturing MSCs, as well as expected causes of culture failures, and appropriate troubleshooting measures.

Materials and methods

1. Experimental Animals

Healthy mice (Balb/c, 4-6 weeks) were used in this study. Mice were housed in clean cages containing woodchip bedding, under a controlled temperature (24±2) and light (12h light/ dark cycle) conditions, with free access to food and water. All procedures were performed according to the Guide for the Care and Use of Laboratory Animals and the ethical standards of our institution [13].

2. Reagents and materials

Dulbecco’s modified Eagle’s medium (DMEM), fetal bovine serum (FBS), L-glutamine, penicillin/streptomycin, amphotericin B, trypsin-EDTA (Euroclone, Italy), TRIzol Reagent (Sigma-Aldrich, USA), reverse transcriptase kit (Promega, USA), ladder (GeneDireX, Taiwan), Ethidium Bromide (Carl Roth, Germany).

3. Isolation and culture of mouse MSC(M)

1. To isolate marrow, the mouse is sacrificed by cervical dislocation. Then, the mouse is brought to a laminar hood.

2. Place the animal in dorsal position on the dissecting board and thoroughly spray the animal skin with 70% ethanol to prevent contamination from the skin.

3. Incise the skin around the perimeter of the hindlimbs, pull the skin down toward the foot, and cut at the anklebone along with the peeled skin. Then, disconnect the hind limbs from the trunk (Fig. 1).

4. Remove the muscles, ligaments, and tendons attached to the bones carefully using sterile surgical scissors, forceps and scalpel.

5. Separate tibias and femurs by bending them in opposite direction and cutting through the knee joint, ensuring that the epiphysis remains intact.

6. Transfer the bones to pre-warmed DMEM medium (37°C) in a sterile Petri dish to preserve viability.

7. Cut the epiphyses of the tibia and femur carefully just below the end of the marrow cavity using sterile, sharp scissors.

8. Insert a 27-gauge needle attached to a 1-ml insulin syringe filled with complete DMEM medium heated to 37°C, supplemented with 1% L-glutamine, 1% penicillin-streptomycin (P/S), and 1.5 µg/ml amphotericin B into the bone cavity and flush the marrow out of the cut end of the bone into a 15 ml Falcon tube. In order to obtain enough marrow cells, repeat this process from both ends of the bone (use 1.4 ml of DMEM for each bone). Add 10% FBS to the bone marrow suspension and gently mix it with a pipette. Transfer the suspension to a cell culture flask. Incubate this flask in an incubator at 37°C in a humidified atmosphere containing 5% CO₂.

9. After flushing out the marrow, transfer the bones to a mortar containing 5 ml of complete DMEM medium, and crush bones gently with pestle using only enough force to crack open the bones and extract the remainder of the bone marrow. Mix gently and transfer the cell suspension to a plastic culture flask. Incubate the flask in an incubator at 37°C and 5% CO₂.

10. Determine yield and viability of the isolated cells using a hemocytometer/automated cell counter and Trypan Blue staining.

11. After 24 h at 37°C, replace the culture medium to remove non-adherent cells and tissue debris with 5 mL of complete DMEM medium (20% FBS). Later on, replace the culture medium daily.

12. On the 5^th day, remove the culture medium and wash the cells with phosphate buffer saline (PBS 1X), then detach the adherent cells by adding 1-1.5 ml of 0.25% trypsin into the flask for 2 min at 37°C. Neutralize trypsin by adding 3 ml of DMEM medium (20% FBS). Transfer the cell suspension into a 15 ml Falcon tube, and centrifuge for 3-5 min at 1000 rpm. Passage the resulting cells at a split ratio of 1:2 or 1:3.

Figure 1. Stepwise procedure of mesenchymal stromal cells isolation from the bone marrow of Balb/c mice

The mouse was sacrificed by a cervical dislocation, and the animal skin is sprayed with 70% ethanol (A). Skin was incised around the perimeter of the hind limbs (B). The foot with peeled skin was cut at the anklebone (C). Hind limbs were disconnected from the trunk, and transferred to a sterile Petri dish (D, E). Muscles, ligaments, and tendons were removed from the bones (F). Bones cleared from the rest of muscles (G). Tibias and femurs were separated by cutting through the knee joint (H), and transferred to pre-warmed DMEM medium in a sterile Petri dish (I). Epiphyses were cut using sterile, sharp scissors (J). Bone marrow was flushed out of the bone (K, L). Bones were crushed gently to extract the remainder of the bone marrow (M). Yield and viability of cells was determined using automated cell counter (N).

4. Gene expression assay for molecular phenotyping

Total RNA was isolated from MSC(M) using TRIzol Reagent. The quantity and quality of the isolated RNA were evaluated by Thermo Scientific NanoDrop 2000. RNA was reversely transcribed into complementary DNA (cDNA) from 1 μg of total RNA in a 20 μl reaction mixture by means of reverse transcriptase kit (Promega, USA), according to the manufacturer’s instruction. PCR of the cDNA samples was applied to detect expression of CD73, CD44, CD105, CD11b, CD34, with GAPDH gene used as a reference. To check expression of each gene, 4 μl of cDNA was added to the gene-specific primers in 25 μl total reaction mixture. Primer sequences for GAPDH and CD34 genes were obtained from the published reports [14, 15], whereas primers for CD11b, CD73, CD44, CD105 genes were designed using NCBI database. Table 1 summarizes gene names, forward and reverse primer sequences, annealing temperatures and expected amplicon length. The PCR conditions were as follows: (1) 10 minutes at 95°C, (2) 35 cycles of 30 seconds at 95°C, 45 seconds at primer annealing temperature, and 45 seconds at 72°C, (3) 10 minutes at 72°C. Following PCR, the amplicons were detected on 2% agarose gel using a 50 bp ladder (GeneDireX, Taiwan) and Ethidium Bromide to visualize the amplicons.

Table 1. Genes assayed, NCBI accession number, forward and reverse primer sequences, annealing temperatures and amplicon sizes for PCR analysis

5. Adipogenic Differentiation

Adipogenic differentiation ability was evaluated in vitro, according to [16], with slight modifications. The cells were plated in 96-well plate in complete DMEM medium (10% FBS). After 24 hours, the medium was replaced by adipogenic induction medium (complete DMEM medium supplemented with 10% FBS, 2 μM dexamethasone, 0.1 mM indomethacin, and 5 μg/ml insulin). Cells cultured in a complete DMEM medium (10% FBS) were used as a negative control. After one week, the cells were fixed with 10% Paraformaldehyde (PFA) for 20 min and stained with Sudan III (1%) to detect the formation of lipid droplets, then washed with distilled water. Lipid droplets were detected by inverted microscope (Olympus IX53, Japan).

6. Osteogenic differentiation

Osteogenic differentiation ability was evaluated according to [17], with slight modifications. Cells were plated in 96 well plate in complete DMEM medium (10% FBS). After 24 hours, the medium was replaced with osteogenic induction medium (complete DMEM medium supplemented with 10% FBS, 10 μM dexamethasone, 10mM β-glycerophosphate, and 50 μM ascorbic acid). Cells cultured in a complete DMEM medium (10% FBS) were used as a negative control. After 1 week, the cells were fixed with 10% Paraformaldehyde (PFA) for 20 min and stained with Alizarin Red (2%) to detect the presence of calcium deposits, then washed with distilled water. Calcium deposits were detected by inverted microscope.

Results

1. Morphology of isolated MSC(M) in culture

MSC(M) were isolated from the femurs and tibias of Balb/c mouse according to their adherence to a culture flask. Using our protocol, we obtained ~ 75-90*10⁶ of BM mononuclear cells (BMMNCs) with 94% viability using flushing process, and ~ 10-20*10⁶ of BMMNCs with 84% viability by crushing process. Isolated MSC(M) settled down within 10 minutes of seeding and showed round-shaped morphology with various sizes. After 24 hours, the MSC(M) attached to the flask surface and non-adherent cells were carefully removed by medium changing. After 24 hours of cultivation, some cells became spindle. On Day 3, the number of spindle-shaped cells increased dramatically. On Day 4, the spindle-shaped cells reached about 60-70% confluence. On Day 5, the cells grew and form 80-90% confluent monolayer (Fig. 2), and cells were passaged on this day.

Figure 2. Morphological features of cultured mouse MSC(M) at passage 0

(A) Rounded-shape cells settled down within 10 minutes of seeding. (B) Following 24 hours of cultivation, some spindle-shaped cells appeared. (C) The ratio of spindle-shaped cells increased on Day 3. (D) On Day 4, the spindle-shaped cells reached about 60-70% confluence. (E) On Day 5 of culture, the cells reached 80-90% confluence, being passaged at this term.

Figure 3. Expression of MSC gene markers detected by RT-PCR and agarose gel electrophoresis (lanes 1 to 6) for the following PCR products: (1) GAPDH (123bp) used as control; (2) CD73 (115 bp); (3) CD44 (136 bp); (4) CD11b (192 bp); (5) CD105 (344 bp); (6) CD34 (215 bp)

2. Characterization of cell surface markers

In this study, MSC(M) isolated from Balb/c mouse were characterized to investigate expression of surface antigens, and the results indicated that the cells were positive for CD73, and CD44, since the bands appeared at the expected distances when PCR products were subjected to electrophoresis in 2% agarose gel. Moreover, there was no detectable CD11b expression, along with only weak expression of CD34 and CD105 (Fig. 3).

3. Adipogenic and osteogenic differentiation

Adipogenic and osteogenic differentiation potential of isolated MSC(M) was tested. Following 7 days of culture under adipogenic induction conditions, MSC(M) showed marked morphological changes compared to the undifferentiated cells (control). They also showed accumulation of several cytoplasmic lipid droplets. After staining with lipophilic Sudan III, the control cells did not show any cytoplasmic changes and were negative for Sudan III staining, while distinct cytoplasmic lipid droplets were observed in MSC(M) grown in adipogenic medium (Fig. 4).

Figure 4. Mesodermal differentiation of MSC(M) at the passage 0

A: Adipogenic differentiation of MSCs: (a) BMSCs after induction with adipogenic medium, showing formation of intracytoplasmic lipid droplets; (b, c). Positive staining of lipid droplets with Sudan III. (B): Osteogenic differentiation: (a). BMSCs after induction with osteogenic medium showed cuboidal morphology (b). Alizarin Red staining indicated dark red precipitation of calcium deposits. (c) Control BMSCs cultured in DMEM medium (10%FBS).

Following 7 days of culture in osteogenic induction medium, MSC(M) showed morphological changes and acquired cubical shape, whereas control cells did not show any morphological changes. After staining with Alizarin Red, the control cells were dye-negative, whereas differentiated cells were positively stained, indicating the presence of calcium deposits (Fig. 4).

Discussion

Cell isolation procedure

Mesenchymal stromal cells (MSCs) are used in many research fields and have sparked great interest in cell therapies due to their ability to differentiate into various cell types [18]. MSC culture was first established by Friedenstein and his colleagues by virtue of the physical propensity of MSCs to adhere to plastic flasks, and the original method has been modified by others [19]. Several methods have been used for isolating MSC(M) including whole marrow direct adherence, density gradient centrifugation, flow cytometry and immunobead methods. However, the latter two methods are considered high in cost and technically difficult [20]. The direct culture method is best to culture high number of MSC(M) within very short time and at high viability rate [21]. It is clearly easier and reduce loss of MSCs compared to density gradient separation approach. However, the cells collected by this method represent a heterogeneous mixture of cells, including hematopoietic cells, endothelial cells and endothelial progenitor cells [11]. This problem was solved using frequent medium change that may prevent adherence of many of the non-MSCs and hematopoietic cells to the culture dishes [2].

Usage of adult MSCs in human therapeutic applications depends on the establishing of preclinical studies with other mammals such as mouse [22]. In order for such therapies to be reproducibly performed in preclinical animal models, a simple, high-yield method for obtaining MSCs is required [19]. In this study, MSC(M) were isolated from the mice aged 4-6 weeks. We obtained high cellular yield, and the isolated cells were able to grow and proliferate within a short period of time. Previous study indicated that age of the animals used as MSCs source directly influences their differentiation, proliferative and metabolism profiles [23]. According to [19], younger mice (sucklings of <3 weeks) produce more proliferative cell cultures. Long bones of newborn mice (up to one week of age) are quite fragile, thus being inconvenient for researchers who have no relevant experience handling them.

- We found that a delay in isolation process from sacrificing the mouse to BM collection and culture, greatly affects the yield and viability of the isolated cells. This step is very critical and requires experience and accuracy during work.

- In this study, MSC(M) were isolated using an adherence method, the culture medium was replaced daily during the first four days of culture, in order to provide the cells with the nutrients required for their growth and proliferation. At the same time, the daily change of the culture media may prevent adherence of many non-MSCs, e.g., hematopoietic populations, to the culture dishes. According to our experience, we do not recommend replacement of the culture medium two or three hours after primary cell culture because we found that this process results in loss of some MSCs and thus obtaining a lower cellular yield.

- Two types of culture media (DMEM or RPMI 1640) supplemented with 20% FBS, 1% L-glutamine, 1% penicillin/streptomycin and 1.5 µg/ml amphotericin B were used in our study in order to choose the optimal medium, and the results demonstrated that the both media are suitable for MSC(M) culture and proliferation, since no differences in cell viability, growth or proliferation were observed.

- Fetal bovine serum (FBS) seems to be the most popular choice of supplements in the culture media. It may play a key role in promoting cell attachment and proliferation [24]. In the current protocol, FBS concentration was increased to 20%, and we found that this concentration was suitable for obtaining sufficient numbers of MSCs within a short period of time.

- After separating bones from the muscles, they were directly transferred to a Petri dish containing 3-4 ml of pre-warmed DMEM medium (37°C), without additives of serum or antibiotics, to preserve cell viability.

- To reduce the possibility of contamination, the bones should not be transferred to the culture media before cleaning it from the muscle.

- To reduce the possibility of contamination, a fresh media should be used to flush the marrow out of the bone rather than using the media in which the bones were placed after separating from the muscle.

- In this study, the marrow was flushed out from both ends of the bone to obtain a high cellular yield, as proposed by [25].

- Only 1.4 ml of culture medium is sufficient for flushing the marrow out of the bone, then the bones could be transferred to a sterile mortar containing 5 ml of culture medium, and gently crushed to extract the remaining bone marrow. We found that this step is very useful to obtain a high MSC(M) yield, because the stromal cells locate near the surface of the bone, which makes it difficult to obtain enough MSCs, even after flushing BM during cell preparation [8].

- In our study, after collecting the BM suspension, it was immediately transferred to the culture flask, without centrifugation or filtration. MSC(M) were cultured into their initial niche composing of stromal cells, extracellular matrix elements, and secreting factors with minimal disturbance, to allow the initial adjusting time for the MSCs in culture, according to [26]. We found this method to be more efficient. However, in our protocol, the culture medium was replaced daily, contrary to what was suggested by [26] who kept the cells in their niche for 4 days without replacing the media.

- Using our modified protocol, we were able to isolate ~ 25% more BMMNCs than the commonly used protocol.

- On the fifth day of culture, MSC(M) reached about 80- 90% confluence. Hence, they were passaged to prevent overgrowth and cell detachment. MSC(M) are strongly attached to the flask and can't be easily detached from the flask using trypsin solution at lower concentration (0.05%). Therefore, a more concentrated trypsin solution (0.25%) was used to detach the cells.

- The trypsinization conditions should be carefully controlled. It is necessary to adhere to the concentration of the trypsin solution used to separate the cells, as well as incubation time. Insufficient trypsin treatment will reduce the yield of cells [11]. On the other hand, bone marrow-derived adherent cells were found to contain different cell types including fibroblasts, hematopoietic progenitor cells, macrophages, endothelial cells and adipocytes [4]. Long-term incubation with trypsin resulting in collection of other unwanted trypsin-resistant cells, e.g., macrophages [19], which firmly adhere to cell culture dishes, whereas MSCs were shown to be more responsive to trypsin [4]. Excessive trypsinisation may also damage cells by striping cell surface proteins. The most prominent problems that researchers may face in the mouse MSC(M) isolation and culture and possible solutions for them are listed in Table 2.

Table 2. Some problems and suggested solutions for mouse MSC(M) isolation and culture

Cell Surface Markers

Mammalian bone marrow contains a myriad of stem cells with distinctive morphological and functional features such as mesenchymal stem cells (MSCs), hematopoietic stem cells (HSCs), multipotent adult progenitor cells (MAPCs) and very small embryonic-like stem cells (VSELs) [12]. Due to growing interest in using MSCs for cell-based therapy, the need to identify MSCs in a definitive way is not only of research interest but also derives from clinical requirements [27].

The isolation of distinct cell types from bone marrow stroma is hindered by the lack of known specific surface markers for those cells. To date, only a set of markers can identify stem/stromal cells from bone marrow, and none of them is unique [1].

In this study, MSC(M) isolated from Balb/c mice were characterized to investigate gene expression of the surface markers, and the results indicated that the cells were positive for (CD73 and CD44), negative for (CD11b), while they showed weak expression of CD34 and CD105 (Fig. 3). These results demonstrated that the isolated cells were MSC-like in morphology, adhesion to plastic surfaces, expression of surface markers, and in adipogenic/osteogenetic differentiation potential. Although the isolated MSC(M) showed characteristics of mesenchymal stromal cells, we suggest that there is a low proportion of hematopoietic stem cells, since the cells were characterized at the passage (P0), and it has been reported that hematopoietic stem cells still exist in the culture even after nine in vitro passages [19]. Increased number of cell passages could result in a significant reduction of hematopoietic stem cells.

Mouse MSCs are generally characterized by positive expression of CD44, CD73, CD105, CD29, CD106, Sca-1, and negative expression of hematopoietic and endothelial markers CD45, CD11b, Ter-119, and CD31 [6]. Our results showed that the surface marker CD profiles for the MSC(M) were compatible with those previously reported.

It has been demonstrated that CD34 expression is not specific for murine hematopoietic cells, as it was shown for human cells. Previous study reported that the expression of CD34 was strain-dependent in mice. Bl/6 MSCs expressed high levels of CD34, with moderate expression by FVB/N MSCs. Both Balb/c and DBA1 MSCs expressed low levels, while MSCs from the 4 standard inbred strains were negative for CD11b [10].

Adipogenic and osteogenic potentials

MSCs are defined by their ability to differentiate and generate cells of mesodermal origin like adipocytes, osteocytes and chondrocytes in culture [6]. The results of mesodermal differentiation assays showed that isolated MSC(M) were able to differentiate into adipocytes and osteocytes in vitro. MSC(M) cultured in adipogenic medium showed morphological changes and displayed accumulation of lipid vacuoles, which stained positively with Sudan III. Lipid droplets in differentiated cells became red due to their affinity for lipophilic Sudan III dye. Similarly, MSC(M) cultured in osteogenic medium showed morphological changes and stained positively with Alizarin Red, indicating presence of calcium deposits. Our results are consistent with previous reports, and demonstrate the opportunity of using these cells in both clinical and research applications.

In the current study, MSC(M) at passage 0 were able to differentiate into adipocyte and osteoblasts like cells within only seven days of incubating with differentiation medium. Meanwhile, many previous studies indicated that adipogenic and osteogenic differentiation takes about three weeks. This slow dynamic may be due to the fact that cell differentiation capability and function decline with repeated passaging [28].

Previous research demonstrated that BMSCs from passage 3 were inferior to bone marrow mononuclear cells (BMMNCs) not only in their chondrogenic differentiation capability but also as candidates for long-term repair of cartilage defects [28]. Previous study reported that MSCs from passage 1 have stronger osteogenic potential in vitro than those of passages 2 and 3, and might be suitable for clinical application to bone tissue engineering [29].

Differentiation of MSCs into various lineages is strictly regulated at multiple sequential steps, being represented by distinct morphological and molecular characteristics [12]. Until now, the mechanism of MSCs trans-differentiation is unclear. There are many internal and external factors that trigger MSCs differentiation.

Conclusion

Increased demand for MSCs in research and medical studies has led scientists to give priority to the development of standardized MSCs isolation and culture methods. In the present study, we have successfully isolated MSC(M) from Balb/c mouse under optimized isolation and culture conditions. We have also listed the most prominent problems that researchers may face and suggested the possible solutions for them. We hope that this simple and practical method will facilitate the study of MSCs, both for examining their biological properties, as well as their therapeutic potential in various murine disease models.

Acknowledgments

The authors are grateful to the Leishmania Center of Epidemiological and Biological Studies, National Commission for Biotechnology (Department of Pharmaceutical Biotechnology). We would like to thank Dr. Ruba Joujeh, Dr. Hassan Alkhoury, Dr. Majd Aljamali, Dr. Fateh Khatib, Ms. Reham Antaki, for their help and support. This research was funded by the University of Aleppo.

References

Rostovskaya M, Anastassiadis K. Differential expression of surface markers in mouse bone marrow mesenchymal stromal cell subpopulations with distinct lineage commitment. PLoS One. 2012; 7(12): 1-12. doi: 10.1371/journal.pone.0051221
Soleimani M, Nadri S. A protocol for isolation and culture of mesenchymal stem cells from mouse bone marrow. Nature Protocols. 2009; 4(1): 102-106. doi: 10.1038/nprot.2008.221
Al-Qaisy B, Yaseen N, Alwachi S, AL-Shammari A. Comparison between three different protocols for isolation and culture of mouse bone marrow derived mesenchymal stem cells. Iraqi J Cancer Med Genet. 2014; 7(1): 26-35.
Nadri S, Soleimani M, Hosseni RH, Massumi M, Atashi A, Izadpanah R. An efficient method for isolation of murine bone marrow mesenchymal stem cells. Int. J. Dev. Biol. 2007; 51: 723-729. doi: 10.1387/ijdb.072352ns
Caplan A. Mesenchymal stem cells: Time to change the name. Stem Cells Transl Med. 2017; 1-7. https://doi.org/10.1002/sctm.17-0051
Schachtele S, Clouser C, Aho J. Markers and methods to verify mesenchymal stem cell identity, potency, and quality. https://www.cellandgene.com/doc/markers-and-methods-to-verify-mesenchymal-stem-cell-identity-potency-and-quality-0001
Oikonomopoulos A, Deen W, Manansala A, Lacey P, Tomakili T, Ziman A, Hommes D. Optimization of human mesenchymal stem cell manufacturing: the effects of animal/xeno-free media. Sci Rep. 2015; 5: 1-11. doi: 10.1038/srep16570
Sung JH, Yang HM, Park JB, Choi GS, Joh JW, Kwon CH, Chun JM, Lee SK, Kim SJ. Isolation and characterization of mouse mesenchymal stem cells. Transpl Proc. 2008; 40: 2649-2654. doi: 10.1016/j.transproceed.2008.08.009
Hu Y, Lou B, Wu X, Wu R, Wang H, Gao L, Pi J, Xu Y. Comparative study on in vitro culture of mouse bone marrow mesenchymal stem cells. Stem Cells Intern. 2018; 1-14. doi: 10.1155/2018/6704583
Peister A, Mellad J, Larson B, Hall B, Gibson L, Prockop D. Adult stem cells from bone marrow (MSCs) isolated from different strains of inbred mice vary in surface epitopes, rates of proliferation, and differentiation potential. Blood. 2004; 103(5): 1662-1668.
doi: 10.1182/blood-2003-09-3070
Ikebe C, Suzuki K. Mesenchymal stem cells for regenerative therapy: optimization of cell preparation protocols. BioMed Research International. 2014; 1-11. doi: 10.1155/2014/951512
Chaudhary JK, Rath PC. A simple method for isolation, propagation, characterization, and differentiation of adult mouse bone marrow-derived multipotent mesenchymal stem cells. J Cell Sci Ther. 2017; 8(1): 1-10. doi: 10.4172/2157-7013.1000261
Guide for the care and use of laboratory animals, Eighth Edition, 2011, National Academy of Sciences, 246 pages.
Roderfeld M, Rath T, Voswinckel R, Dierkes C, Dietrich H, Zahner D, Graf J, Roeb E. Bone marrow transplantation demonstrates medullar origin of CD34+ fibrocytes and ameliorates hepatic fibrosis in Abcb4_/_ mice. Hepatology. 2010; 51:267-276.
doi: 10.1002/hep.23274
Tohidi F, Toosi M, Azimian H, Khademi S, Fardid R, Sarab GH. The gene expression level of p53 and p21 in mouse brain exposed to radiofrequency field. Int J Radiat Res. 2015; 13(4): 337-343. doi: 10.7508/ijrr.2015.04.007
Sibov Y, Severino P, Marti LC, Pavon LF, Oliveira DM, Tobo PR, Campos AH, Paes AT, Amaro E, Gamarra LF, Moreira-Filho CA. Mesenchymal stem cells from umbilical cord blood: parameters for isolation, characterization and adipogenic differentiation. Cytotechnology. 2012; 64: 511-521. doi: 10.1007/s10616-012-9428-3
Castro-Silva I, Castro L, Machado J, Nicola M, Granjeiro J. Isolation of human umbilical cord blood-derived osteoprogenitor cells: a promising candidate for cell-based therapy for bone repair. Einstein. 2011; 9: 449-455. doi: 10.1590/s1679-45082011ao2196
Baustian C, Hanley S, Ceredig R. Isolation, selection and culture methods to enhance clonogenicity of mouse bone marrow derived mesenchymal stromal cell precursors. Stem Cell Res Ther. 2015; 6(151): 1-13. doi: 10.1186/s13287-015-0139-5
Zhu H, Guo Z, Jiang X, Li H, Wang X, Yao H, et al. A protocol for isolation and culture of mesenchymal stem cells from mouse compact bone. Nature Protoc. 2010; 5(3): 550-560. doi: 10.1038/nprot.2009.238
Hasoon MF, Nader B, Mohammed MH. A study of the bone marrow derived mesenchymal stromal cells in rats - proliferation and immunophynotypic markers. Malaysian J Vet Res. 2018; 9(1): 73-80.
Abdullah RH, Yaseen NY, Saleh SM, Mohamed MH, Al-Shammari A. Direct and simple method for mesenchymal stem cells isolation, culturing and detection. Int J Stem Cell Res. 2018; 5(2): 1-5. doi: 10.23937/2469-570X/1410054
Tropel Ph, Noel D, Platet N, Legrand P, Benabid A, Berger F. Isolation and characterisation of mesenchymal stem cells from adult mouse bone marrow. Exp Cell Res. 2004; 295: 395-406. doi: 10.1016/j.yexcr.2003.12.030
Fafián-Labora J, Fernández-Pernas P, Fuentes I, De Toro J, Oreiro N, Sangiao-Alvarellos S, Mateos J, Arufe MC. Influence of age on rat bone marrow mesenchymal stem cells potential. Sci Rep. 2015; 5: 1-20. doi: 10.1038/srep16765
Wang X, Yang J, Chen X, Pan X. Establishment and characterization of a fibroblast-like cell line from Anabarilius grahami (Cypriniformes: Cyprinidae). Dongwuxue Yanjiu. 2012; 33(E5-6): E89-E97. doi: 10.3724/SP.J.1141.2012.E05-06E89
Madaan A, Verma R, Singh AT, Jain SK, Jaggi M. A stepwise procedure for isolation of murine bone marrow and generation of dendritic cells. Journal of Biological Methods. 2014; 1(e1): 1-6. doi: 10.14440/jbm.2014.12
Huang S, Xu L, Sun Y, Wu T, Wang K, Li G. An improved protocol for isolation and culture of mesenchymal stem cells from mouse bone marrow. J Orthop Transl. 2015; 3(1): 26-33. doi: 10.1016/j.jot.2014.07.005
Augello A, Kurth TB, Bari CD. Mesenchymal stem cells: a perspective from in vitro cultures to in vivo migration and niches. Eur Cell Mater. 2010; 20: 121-133. doi:10.22203/ecm.v020a11
Jiang T, Xu G, Wang Q, Yang L, Zheng L, Zhao J, Zhang X. In vitro expansion impaired the stemness of early passage mesenchymal stem cells for treatment of cartilage defects. Cell Death Dis. 2017; 8:1-12. doi: 10.1038/cddis.2017.215
Chen J, Sotome S, Wang J, Orii H, Uemura T, Shinomiya K. Correlation of in vivo bone formation capability and in vitro differentiation of human bone marrow stromal cells. J Med Dent Sci. 2005; 52(1): 27-34. PMID: 15868738

" ["~DETAIL_TEXT"]=> string(38539) "