ISSN 1866-8836
Клеточная терапия и трансплантация

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Volume 1, Number 1
06/18/2008
Volume 1, Number 1
Editor-in-Chief
Afanasyev B. V. (St. Petersburg, Russia)
Co-Editors-in-Chief
Wagemaker G. (Rotterdam, Netherlands)
Zander A. R. (Hamburg, Germany)
Deputy Editor
Chukhlovin A. B. (St. Petersburg, Russia)
Fehse B. (Hamburg, Germany)
Novik A. А. (Moscow, Russia)
Managing Editor
Claudia Koltzenburg (Hamburg, Germany)
Editorial Board
Aleynikova O. (Minsk, Belarus)
Alyansky A. (St. Petersburg, Russia)
Anagnostou A. (Boston, USA)
Andreeff M. (Houston, USA)
Bacher U. (Hamburg, Germany)
Baуkov V. (St. Petersburg, Russia)
Baranov V. S. (St. Petersburg, Russia)
Barkhatov I. (St. Petersburg, Russia)
Baum C. (Hannover, Germany)
Bilko N. (Kiev, Ukraine)
Borset M. (Trondheim, Norway)
Buechner Th. (Muenster, Germany)
Bykov V. (St. Petersburg, Russia)
Dini G. (Genoa, Italy)
Drize N. (Moscow, Russia)
Egeland T. (Oslo, Norway)
Elstner E. (Berlin, Germany)
Emanuel V. (St. Petersburg, Russia)
Everaus H. (Tartu, Estonia)
Ferrara J. (Ann Arbor, USA)
Fibbe W. (Leiden, Netherlands)
Galibin O. (St. Petersburg, Russia)
Ganser A. (Hannover, Germany)
Granov D. (St. Petersburg, Russia)
Ivanov R. (Moscow, Russia)
Klimko N. (St. Petersburg, Russia)
Kolb H.-J. (Muenchen, Germany)
Konopleva M. (Houston, USA)
Koza V. (Pilsen, Czech Republic)
Kroeger N. (Hamburg, Germany)
Malikov A. (St. Petersburg, Russia)
Mikhailova N. (St. Petersburg, Russia)
Mentkevich G. (Moscow, Russia)
Nagler A. (Tel Hashomer, Israel)
Nemkov A. (St. Petersburg, Russia)
Neth R. (Hamburg, Germany)
Nevorotin A.J. (St. Petersburg, Russia)
Ostertag W. (Hamburg, Germany)
Palutke M. (Detroit, USA)
Roumiantsev A. G. (Moscow, Russia)
Savchenko V. G. (Moscow, Russia)
Smirnov A. V. (St. Petersburg, Russia)
Stamm C. (Berlin, Germany)
Tetz V. (St. Petersburg, Russia)
To B. (Adelaide, Australia)
Totolian A. A. (St. Petersburg, Russia)
Uss A.L. (Minsk, Belarus)
Vilesov A. (St. Petersburg, Russia)
Westenfelder Ch. (Salt Lake City, USA)
Wisloff F. (Oslo, Norway)
Zubarovskaya L. (St. Petersburg, Russia)
Zvartau E. (St. Petersburg, Russia)
In this Issue

Foreword

To the editorial board and readers of “Cellular Therapy and Transplantation”

Dear friends,
Not so long ago, it would have been hard for me to imagine that I would be writing a welcome letter for the pilot issue of a specialized scientific journal. However, as we say in Russia, mysterious are the ways of the Lord. As things turned out, the topics of this Journal, and especially, its aims and tasks, have proven very close to me. In September 2007, the R. M. Gorbacheva Memorial Institute of Child Hematology and Transplantology was opened at the St. Petersburg State I. Pavlov Medical University. The Gorbachev Foundation, the National Reserve Bank, and the Russian Ministry of Public Health Care were among the initiators of this modern medical department. They have done their best to afford construction of a representative building, acquisition of clinical equipment and medical drugs for the new Institute. Many specialists from this Institute have received the opportunity of undergoing professional training in foreign countries. The Institute is now the largest Russian institution operating in this field of medicine. In the near future, 400 to 500 bone marrow transplantations will be carried out annually. Encouraging perspectives exist for the Institute, and, hence, for the children suffering from leukemia. When performing such a highly sophisticated activity, many issues depend on broad interactions and on shared experience with the best medical and research centers, both in Europe and worldwide. I was happy to hear that the Institute has found the opportunity to organize annual scientific symposia in memory of Raisa Maximovna. Involvement in this international “Cellular Therapy and Transplantation” Journal will provide another method of exchange of novel results and ideas. A Journal with this specific scientific focus represents realistic hopes for recovery for children and their healing from such terrible diseases as leukemia. With this mind, I wish the new Journal every success. Way to go!

Yours Mikhail Gorbachev

Editorial

A meeting point for different lines of thought

Boris Vladimirovich Afanasyev
and Axel Rolf Zander

Keynote

Articles

A comparative study of HLA-A and HLA-В antigens and haplotype distribution among donors of hematopoietic stem cells from Russian and German regions

Ludmila N. Bubnova1, Galina A. Zaitseva2, Ludmila V. Erokhina1, Andrej S. Berkos1, Natalija V. Reutova1, Elena V. Belyaeva1, Marina N. Petrovskaya3, Natalija K. Ignatova4, Ella Ye. Koudinova5, Vera M. Minina6


A New Approach to Therapy for Acute GVHD

James L.M. Ferrara, M.D. 1,2 and John E. Levine, M.D.1,2

Optimization of the indications for allogeneic stem cell transplantation in Acute Myeloid Leukemia based on interactive diagnostic strategies

Maite Hartwig1, Axel Rolf Zander1, Torsten Haferlach2, Boris Fehse1,3,Nicolaus Kröger1, Ulrike Bacher1*

Efficacy and safety of high-dose chemotherapy with autologous hematopoietic stem cell rescue for relapsed/refractory Hodgkin's lymphoma patients in former USSR countries. Retrospective analysis of data from four transplantation centers in Belarus, Russia and the Ukraine

Ptushkin V. V.1, Afanasyev B. V.3, Zhukov N. V.1, Uss A. L.2, Karamanesht E. E.4, Milanovich N. F.2, Mikhaylova N. B.3,
Korenkova I. S.4, Minenko S. V.1, Demina E. A.1, Zmachinski V. A.2, Pugachev A. A.3, Borodkin S. V.4

Review Articles

Hepatocyte growth factor (HGF) in the pathogenesis of multiple myeloma

Magne Børset1,2, Therese Standal1, Anders Waage1,3 and Anders Sundan1

Editorial

A meeting point for different lines of thought

Boris Vladimirovich Afanasyev
and Axel Rolf Zander

Keynote

Raisa Gorbacheva Memorial Lecture Treatment of Acute Myeloid Leukemia: Present Status and New Directions

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Thomas Büchner

The article is introduced by a tribute to the huge merits of Mrs. Raisa Gorbacheva's anti-leukemia campaign. Raisa Gorbacheva and her husband, Mr. Michael Gorbachev, have contributed greatly to the arrangement and funding of childhood leukemia treatment in Russia. The review article also covers the basic issues to do with acute myeloid leukemia (AML) treatment, including the general concepts of myeloablative therapy. Over four decades, improvements in therapeutic approaches have resulted in a gradual increase in complete remission rates and general survival of AML patients. However, further intensification of conventional treatments failed to increase the patients' long-term survival. A significantly lower survival rate among older patients (>60 years of age) is found when using this approach. Recent developments are associated with the usage of chromosome and gene aberrations as valuable markers to predict the treatment results and survival in AML. For example, a mutated nucleophosmin 1 gene in the absence of a FLT3 mutation is an age-independent predictor of a favorable outcome in AML. Decisive progress in AML treatment has been achieved when applying intensive chemotherapy followed by allogeneic transplantation of hematopoietic stem cells (allo-HSCT). This approach is clearly superior to conventional therapy in terms of relapse-free survival. However, comparative efficiency for different therapies presents some statistical controversies (e.g., biased patient selection in Matched Pair analysis). Allo-HSCT is still associated with considerable transplant-associated mortality, thus affecting overall survival rates. To avoid early mortality, a reduced-intensity conditioning may be considered, especially for older patients. Most clinical trials in AML are performed as multicentre therapeutic trials (e.g., within the European Leukemia Network): thus providing faster progress in the development of a more efficient AML treatment.

Articles

A comparative study of HLA-A and HLA-В antigens and haplotype distribution among donors of hematopoietic stem cells from Russian and German regions

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Ludmila N. Bubnova1, Galina A. Zaitseva2, Ludmila V. Erokhina1, Andrej S. Berkos1, Natalija V. Reutova1, Elena V. Belyaeva1, Marina N. Petrovskaya3, Natalija K. Ignatova4, Ella Ye. Koudinova5, Vera M. Minina6


1Russian Research Institute of Hematology and Transfusiology, St.Petersburg; 2Kirov Research Institute of Hematology and Blood Transfusion, Kirov; 3N.Ya.Klimova Nyzhegorodsky Blood Bank, Nyzhni Novgorod; 4Samara Regional Blood Bank, Samara;
5Rostov Regional Blood Bank, Rostov-on-Don; 6Sverdlovsk Blood Bank, Pervouralsk, Russia

Genetic polymorphism in the HLA system is extremely high, thus rendering a search for individuals exhibiting identical genetic characteristics difficult. Meanwhile, successful allografting of unrelated donor hematopoietic stem cells (allo-HSCT) is determined mainly via genetic similarity between the recipient and donor. A Republican Register that unites the databases of HLA-typed donors from the Russian and Kirov Research Institutes of Hematology and Blood Transfusion, and the blood banks of Nyzhni Novgorod, Rostov-on-Don, Samara, and Pervouralsk has been cooperating for several years with the Stefan Morsch Registry in Germany, performing bilateral donor searches for patients with hemoblastosis.

The study has shown that the most pronounced differences in prevalence, both for certain antigens and their haplotypes, are observed between the general cohorts of the German and Russian Registers. Donors from St. Petersburg and Nyhzni Novgorod express maximal similarity in their genetic features. The donors from Samara Region are, for some characteristics, more related to German donors, whereas donors from Kirov possess some features that are typical to Northern folk. This data confirms an urgent need for expansion of the Russian Donor Registry, since the probability of finding a donor in the Russian population is sufficiently higher when performing the search in a local Registry.

Articles

A New Approach to Therapy for Acute GVHD

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James L.M. Ferrara, M.D. 1,2 and John E. Levine, M.D.1,2

1Department of Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan; 2Blood and Marrow Transplantation Program, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan


Address correspondence:
Dr. Ferrara at 1500 E. Medical Center Dr., 5303 Cancer Center, Ann Arbor, Michigan, 48109-0941
or at Ferrara@spam is badumich.edu

Graft-versus-host disease (GVHD) is a principal cause of morbidity following allogeneic hematopoietic cell transplantation (HCT). Multiple pre-clinical studies have shown that tumor necrosis factor-α (TNFα) is an important effector of experimental GVHD. Patients treated with etanercept and steroids were more likely to achieve complete response than were patients treated with steroids alone. This difference was observed in HCT recipients of both related donors and unrelated donors. Cytokine blockade may become an important element of treatment for GVHD in the future.

Articles

Optimization of the indications for allogeneic stem cell transplantation in Acute Myeloid Leukemia based on interactive diagnostic strategies

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Maite Hartwig1, Axel Rolf Zander1, Torsten Haferlach2, Boris Fehse1,3,Nicolaus Kröger1, Ulrike Bacher1*

1Interdisciplinary Clinic for Stem Cell Transplantation, University Medical Center Hamburg, Germany; 2MLL, Munich Leukemia Laboratory, Munich, Germany; 3Experimental Pediatric Oncology and Hematology, Hospital of the Johann Wolfgang Goethe-University, Frankfurt am Main, Germany


Correspondence:
*Dr. med. Ulrike Bacher, MD, Interdisciplinary Clinic for Stem Cell Transplantation,
University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany


Tel. 00494428034154, Fax. 00494428038097, Email: u.bacher@uke.de

The indications for allogeneic stem cell transplantation (SCT) in Acute Myeloid Leukemia (AML) represent a real challenge due to the clinical and genetic heterogeneity of the disorder. Therefore, an optimized indication for SCT in AML first requires the determination of the individual relapse risk based on diverse chromosomal and molecular prognosis-defining aberrations. A broad panel of diagnostic methods is needed to allow such subclassification and prognostic stratification: cytomorphology, cytogenetics, molecular genetics, and immunophenotyping by multiparameter flow cytometry. These methods should not be seen as isolated techniques but as parts of an integral network with hierarchies and interactions. Examples for a poor risk constellation as a clear indication for allogeneic SCT are provided by anomalies of chromosome 7, complex aberrations, or FLT3-length mutations. In contrast, the favorable reciprocal translocations such as the t(15;17)/PML-RARA or t(8;21)/AML1-ETO are not indications for SCT in first remission due to the rather good prognosis after standard therapy. Further, the indication for SCT should include the results of minimal residual disease (MRD) diagnostics by polymerase chain reaction (PCR) or flow cytometry. New aspects for a safe and fast risk stratification as basis for an optimized indication for SCT in AML might be provided by novel technologies such as microarray-based gene expression profiling. 

Articles

The influence of autologous marrow mesenchymal stem cell infusion on hematopoiesis reconstitution after hematopoietic stem cells autotransplantation in children with oncological and hematological diseases

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Yanina Isaikina, Nina Minakovskaya, Olga Aleinikova

Belarusian Research Centre for Pediatric Oncology and Hematology, Minsk, Belarus

Tel. +375 17 202 40 89, fax 202-42-22, e-mail: yaninai@mail.ru

Aim

This investigation was undertaken to study the possibility for the application of mesenchymal stem cells (MSCs) for hematopoiesis support and reduction of the neutropenia period after autologous HSCs transplantation for children with oncohematological disorders and graft insufficiency of CD34+ cells/kg.

Patients and methods

24 children, who after collection of hematopoietic stem cells (HSCs) had low numbers of CD34+ (≤ 2,5 x106/kg) in autotransplant, were involved in our investigation. Autologous co-transplantation of MSCs was used for 7 adolescents; and 17 patients who were only given HSCs represented a control. The number of polychemotherapy cycles depended on the specific therapy response, relapse development, and the refractory to therapy, and varied from 4 to 10 cycles. MSCs were isolated from the bone marrow (BM) of patients up to 30–50 days before the autologous transplantation and expanded in vitro. CFU-F analysis was carried out for all patients. Statistical analysis was carried out with the help of STATISTICA 6.0 software. Difference reliability in groups during transplant parameters analysis was evaluated by the Mann-Whitney test, and the correlation degree between parameters by the Spearman test.

Results

About 25 ± 6.9 ml of bone marrow was utilized in order to obtain MSCs. The CFU-F number was about 5.26 ± 0.6 colonies per 105 bone marrow mononuclear cells. The MSCs number had increased an average ~104 times after expansion in vitro for each patient. The data analysis revealed a statistically reliable dependence between the high-dose chemotherapy cycles number received by patients before bone marrow collection and MSCs growth time until a monolayer in primary culture (r = 0.79, p = 0.03) formed. The median number of MSCs reinfused into the patient was 0.6 (range 0.3–1.1) х 106 MSCs/kg in one hour after HSCs transplantation. In the case of co-transplantation, the MSCs neutrophil recovery > 500/µl was in 10 days (range, 9 to 11 days), ≥ 1000/µl in 11days (range, 10 to13 days) compared to 13 days (range, 11 to 15 days), and 14 days (range, 13 to19 days) respectively, in the control group (р = 0.002 and р = 0.001 correspondingly). A reticulocyte number of ≥ 1‰ was observed by 10 days (range 9 to 12 days) and 14 days (range 11 to 17 days), respectively (р = 0.004).

Conclusion

We determined an accelerated engraftment of HSCs transplant with low number CD34+ cells/kg in cases of autologous MSCs co-transplantation for children with malignant disorders. This approach is possible for children who have undergone prolonged myelotoxic and radiotherapy to expanse MSCs to efficient for co-transplantation volume.

Articles

Efficacy and safety of high-dose chemotherapy with autologous hematopoietic stem cell rescue for relapsed/refractory Hodgkin's lymphoma patients in former USSR countries. Retrospective analysis of data from four transplantation centers in Belarus, Russia and the Ukraine

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Ptushkin V. V.1, Afanasyev B. V.3, Zhukov N. V.1, Uss A. L.2, Karamanesht E. E.4, Milanovich N. F.2, Mikhaylova N. B.3,
Korenkova I. S.4, Minenko S. V.1, Demina E. A.1, Zmachinski V. A.2, Pugachev A. A.3, Borodkin S. V.4

1Bone Marrow Transplantation Department, N. N. Blokhin Cancer Research Center, RAMS, Moscow, RF; 2Republican Center for Hematology and Bone Marrow Transplantation, Minsk, Belarus; 3R.M.Gorbacheva Memorial Institute of Children Hematology and Transplantation, and Hematology, Transfusiology and Transplantology Department, St. Petersburg State Medical I. Pavlov University,
Russian Federation; 4Kiev Center for Bone Marrow Transplantation, Kiev, Ukraine


Presenting author
Ptushkin Vadim Vadimovich
Postal address
117997, Leninsky prospect, 117, Moscow, Federal Center of Pediatric Hematology/Oncology/Immunology, Ministry of Health and Social Development, Russia. Head, Department of Clinical Oncology, Telephone +7-903-199-51-69,  Fax +7-495-937-50-24,
E-mail: vadimvadim@spam is badinbox.ru

High-dose chemotherapy (HDC) with autologous stem cell transplantation support is a routine treatment approach for relapsed or refractory Hodgkin's lymphoma (HL) patients. Unfortunately, HDC is much less common in the former USSR republics; among other reasons due to a lack of information about the efficacy and safety of this treatment as performed at local centers.

We analyzed the outcome for 184 HL patients receiving HDC in the former USSR republics between January 1990 and March 2003. Most patients had primary refractory disease (44.8%), early (27.2%) or multiple (21.6%) relapses. Restaging revealed stage III–IV disease in 69%, and B-symptoms in 53% of cases. The patients received a mean of 9 (2 to 34) courses of standard chemotherapy prior to HDC.

HDC yielded complete response or complete response uncertain (CR/CRu) in 68.2% of cases, and the 5-year overall survival (OS) rate was 60%; freedom from treatment failure (FFTF) survival was 41.5% with a median follow-up of 30 months (3 to 139 months). As estimated with respect to disease status, the 5-year FFTF was 35% among patients with primary refractory disease, 46.4% in patients with multiple relapses, and 59.2% in patients with early sensitive relapse. The early death rate was 5.4%, but has demonstrated a considerable decreasing trend over recent years (1.4% in 2000–2003). The HDC with autologous hematopoietic stem cell rescue procedure performed at transplant centers in the former USSR republics is associated with low mortality and satisfactory FFTF for patients with primary refractory or relapsed Hodgkin's disease.

Articles

The role of аnti-thymocyte globulin in preventing graft rejection and acute graft-versus-host disease after allogenic hematopoietic stem cell transplantation

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Zalyalov Y. R., Ganapiev B. A., Potapenko V. G., Mikhailova N. B., Afanasyev B. V.

R. M.Gorbacheva Memorial Institute of Hematology and Transplantology, and Department of Hematology, Transfusiology and Transplantology, St. Petersburg State Medical I. Pavlov University

Acute GVHD and graft rejection are the main early complications of allo-SCT. In our research, we analyzed the probability of development of early complications in 109 patients with different oncohematological diseases. We evaluated the results of 112 allo-SCTs from related and unrelated donors subjected to myeloablative and nonmyeloablative conditioning regimens, either with or without ATG. The usage of ATG provides effective control over aGVHD, without increasing the risk of a relapse of the basic disease, and reduces the probability of graft rejection to 7%. Consequently, our data on ATG application in allo-HSCT demonstrates its ability to effectively decrease the risk of early complications post-transplant, thus favoring an increase of 4-year overall survival, in comparison to the control group, where ATG was not used.

Articles

The logistic regression model in the statistical justification of the cost of hematopoietic stem cell transplantation

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Dmitry A. Bagge, Boris I. Smirnov, Boris V. Afanasyev

R. M. Gorbacheva Memorial Institute of Children Hematology and Transplantation, and St. Petersburg State Medical I. Pavlov University, Russia

The logistic regression model allows the calculation of the minimal acceptable cost of HCT, having non-random impact on HCT outcome, under which the probability of a positive outcome is 50%. There were 209 patients enrolled in the study, who received autologous HCT, and allogenic related and unrelated HCT. The non-random cost and medical parameters connected with patient status were defined before HCT and HCT outcomes. The application of reduced toxicity (RTCR) or myeloablative conditioning regimens (MCR), the presence of relapse before HCT, and the cost of drugs and blood transfusion all have an influence on the outcome, and the weight coefficients of these parameters were calculated. This allows the connection of costs and clinical parameters, and the calculation of the minimal acceptable cost of HCT.

Review Articles

Cord blood - from a disposable byproduct of human birth into a precious source for life saving therapies

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Gal Goldstein1, Amos Toren1, Arnon Nagler2

1Pediatric Hemato-Oncology Department, The Edmond and Lily Safra children's Hospital;
2Division of Hematology and Cord Blood Bank, Chaim Sheba Medical Center, Tel Hashomer and Sackler school of Medicine, Tel Aviv University, Tel Aviv, Israel

The review article concerns the transplantation of hematopoietic stem cells (HSCs) derived from cord blood (CB). This approach was previously used in pediatric settings. In partu procedures of CB HSCs harvesting, along with the routine methods of their quality control (i.e., HLA typing, testing for infectious pathogens) are listed in brief. Ca. 250,000 CB units are now stored in 35 blood banks in 21 countries worldwide. Some ethical problems with application of CB cells could arise during their long-term storage. The authors point to the controversies associated with the development of private cord blood banks (capacity is estimated at 600,000 CB units), due to indefinite and/or indefensible terms of their storage for eventual transplants. The specific potential of CB HSCs is limited by small sample volume; however relatively low numbers of HSCs with high proliferative activities, along with lower counts of T lymphocytes and their higher immunological tolerance enable HSC transplants at reduced rejection risk and lower GvHD rates.

Clinical experience with CB HSC transplantation is compared for different centers, where the high efficiency of this approach is shown, being, however, associated with longer terms of hematopoietic recovery when compared to bone marrow transplants. A minimal acceptable HSC CB dose is estimated as 1.5-2.5x107 nucleated cells per kg body mass of a patient. The main areas of CB HSC transplantation are described, i.e., related or unrelated transplants, performed in non-cancer and malignant disorders. The authors point to scarce data comparing the efficiency of HSCs derived from cord blood versus bone marrow samples.

Special attention is paid to CB HSC transplantation in non-malignant conditions with bone marrow aplasia associated with unacceptably high non-engraftment risk. Good results of CB HSCT are demonstrated in hemoglobinopathies and mucopolysaccharidoses. When administering CB HSCs to adult patients, non-myeloablative conditioning regimens are proposed, despite the poorly defined efficiency of such an approach. An opportunity for simultaneous transplants of two or more HSC units is considered, including a unit of CB HSCs. An option of intraosseous CB HSC injection is also discussed. In vitro techniques of CB HSC expansion are under development, in spite of scarce data on their proliferative rates and differentiation ability. As an additional stimulus, injection of mesenchymal stem cells together with CB HSCs was recently proposed. In conclusion, the possible usage of normal CB HSCs to correct genetic deficiencies in children is described. CB HSCs' pluripotency may be also applied to the repair of various tissue lesions, e.g., myocardial infarction, or vascular defects.

Review Articles

Hepatocyte growth factor (HGF) in the pathogenesis of multiple myeloma

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Magne Børset1,2, Therese Standal1, Anders Waage1,3 and Anders Sundan1

1Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; 2Department of Immunology and Transfusion medicine, St. Olavs University Hospital, Trondheim, Norway; 3 Department of Hematology, St. Olavs University Hospital, Trondheim, Norway.

Corresponding author:
Magne Børset, Norwegian University of Science and Technology, Faculty of Medicine, Department of Cancer Research and Molecular Medicine, Medical Technical Research Center, N-7489 Trondheim, Norway

Telephone: + 47 72573038,
Fax: + 47 73598801,
E-mail: magne.borset@ntnu.no

HGF is emerging as a cytokine with an important role in the pathophysiology of multiple myeloma. Originally identified and described as a growth factor for hepatocytes, HGF was later found to have mitogenic, motogenic, or morphogenic effects on several cell types through its interaction with the tyrosine kinase receptor c-Met. This cytokine–receptor pair is implicated in the development and promotion of several types of cancer. The expression of both HGF and c-Met by myeloma cells is one of the traits distinguishing these cells from healthy plasma cells, and seems to be an early step in tumor development. HGF and c-Met have an effect on proliferation, migration, and adhesion of myeloma cells; and research suggests that myeloma cell-produced HGF is an important factor in angiogenesis and bone destruction seen in the majority of patients with multiple myeloma.

Review Articles

Mechanisms facilitating regenerative therapies with multipotent marrow stromal cells

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Florian Tögel, Christof Westenfelder

Department of Medicine/Nephrology and VA Medical Center, University of Utah, USA


Correspondence:
University of Utah, Department of Medicine/Nephrology and VA Medical Center, Nephrology Research Laboratory (151M), 500 Foothill Blvd, Salt Lake City, UT 84148, USA


E-mail: Florian.Toegel@hsc.utah.edu or Christof.Westenfelder@hsc.utah.edu

Cell therapy has become a promising new treatment approach for a large number of different diseases, and applications are continually being developed. Bone marrow derived stem cells are currently being tested in clinical trials and have been shown to be promising new therapeutic vehicles. Multipotent marrow stromal cells (MSCs) are a bone marrow derived cell type that can be easily cultured and expanded in vitro and have a broad range of potential and actual therapeutic applications. The mechanism of action of MSCs in the therapeutic situation depends on the disease, and involves differentiation, immunomodulation, paracrine, and anti-apoptotic mechanisms. These mechanisms are discussed in detail in this manuscript.