rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2013-1203rsp-1113Research ArticleСтатьиArticlesМезенхимальные клетки костного мозга -перспективы использования при ревматических болезняхBone marrow mesenchymal cells: Promises for use in rheumatic diseasesАнаньеваЛ. П.AnanyevaLidia Petrovna

заведующая лабораторией микроциркуляции и воспаления отдела сосудистой патологии д.м.н.

zaveduyushchaya laboratoriey mikrotsirkulyatsii i vospaleniya otdela sosudistoy patologii d.m.n.

ananieva@irramn.ruАлекперовР. Т.AlekperovR T

старший научный сотрудник лаборатории микроциркуляции и воспаления отдела сосудистой патологии д.м.н.

starshiy nauchnyy sotrudnik laboratorii mikrotsirkulyatsii i vospaleniya otdela sosudistoy patologii d.m.n.

НасоновЕ. Л.NasonovE L

директор академик РАМН, д.м.н.

direktor akademik RAMN, d.m.n.

Федеральное государственное бюджетное учреждение Научно-исследовательский институт ревматологии» РАМН, Москва201315022013511№1 (2013)5967Copyright © Ананьева Л.П., Алекперов Р.Т., Насонов Е.Л., 20132013Ананьева Л.П., Алекперов Р.Т., Насонов Е.Л.Ananyeva L.P., Alekperov R.T., Nasonov E.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/1113

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References<div><p>Tyndall A. Successes and failures of stem cell transplantation in autoimmune diseases. Hematology Am Soc Hematol Educ Program 2011;2011:280-4.</p><p>Chen Y., Shao J.Z., Xiang L.X. et.al. Mesenchymal stem cell: a promising candidate in regenerative medicine. Int J Biochem Cell Biol 2008;40:815-20.</p><p>Müller I., Lymperi S., Dazzi T. Mesenchymal stem cell therapy for degenerative inflammatory disoders. Curr Opin Organ Transplant 2008;13:639-44.</p><p>Friedenstein A.J., Petrakova K.V., Kurolesova A.I., Frolova G.P. Heterotopic of bone marrow. Analysis of precursor cells for octeogenic and hematopoetic tissue. Transplantation 1968;6:230-47.</p><p>Roberts S., Genever P., McCaski A., De Bari C. Prospects of stem cell therapy in osteoarthritis. Regen Med 2011;6:351-66.</p><p>Prockop D.J. Marrow stromal cells as stem cells for non-hematopoetic tissues. Science 1997;278:71-4</p><p>Domimici M., Le Blank K., Mueller I. et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006;8:315-7.</p><p>Pittenger M.F., Mackay A.M., Beck S.C. et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999;284:143-7.</p><p>Horwitz E., Le Blanc К., Dominici M. et al. Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy 2005;7:393-5.</p><p>Rasmusson I. Immune modulation by mesenchymal stem cells. Exp Cell Res 2006;312:2169-79.</p><p>Le Blanc K., Tammik C., Rosendahl K. et al. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol 2003;31:890-6.</p><p>Majumdar M.К., Keane-Moore M., Buyaner D. et al. Characterization and functionality of cell surface molecules on human mesenchymal stem cells. J Biomed Sci 2003;10:228-41.</p><p>Schwartz R.H. A cell culture model for T lymphocyte clonal anergy. Science 1990;248:1349-56.</p><p>Nauta A.J., Fibbe W.E. Immunomodulatory properties of mesenchymal stromal cells. Blood 2007;110:3499-506.</p><p>Corcione A., Benvenuto F., Ferretti E. et al. Human mesenchymal stem cell modulate B-cells functions. Blood 2006;107:367-72.</p><p>Honczarenko M., Le Y., Swierkowski M. et al. Human BMSC express a distinct set of biologically functional chemokine receptors. Stem Cells 2006;24:1030-41.</p><p>DelaRosa O., Lombardo E., Beraza A. et al. Requirement of INF-gamma-mediated indoleamine 2,3-dioxigenase expression in the modulation of lymphocyte proliferation by human adipose-derived stem cells. Tissue Eng 2009;15:2795-806.</p><p>Zappia E., Casazza S., Pedemonte E. et al. Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis indusing T-cell anergy. Blood 2005;106:1755-61.</p><p>Sheng H., Wang Y., Jin Y et al. A critical role of INF in priming MSC-mediated supression of T cell proliferation through up-regulation of B7-H1. Cell Res 2008;18:846-57.</p><p>Di Nicola M., Carlo-Stella C., Magni M. et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 2002;99:3838-43.</p><p>English K., Ryan J.M., Tobin L. et al. Cell contact, prostaglandin E(2) and transforming growth factor beta 1 play non-redundant roles in human mesenchymal stem cell induction of CD4+CD25 (High) forkhead box P3+ regulatory T-cells. Clin Exp Immunol 2009;156:149-60.</p><p>Yang S.H., Park M.J., Yoon I.H. et al. Soluble mediators from mesenchymal stem cell suppress T-cell proliferation by inducing IL-10. Exp Mol Med 2009;41:315-24.</p><p>Sato K., Ozaki K., Oh I. et al. Nitric oxide plays a critical role in supression of T-cell proliferation by mesenchymal stem cells. Blood 2007;109:228-34.</p><p>Ren G., Zhang L., Zhao X. et al. Mesenchymal stem cell-mediated immunosupression occurs via cjncerted action of chemokines and nitric oxide. Cell Stem Cell 2008;2:141-50.</p><p>Rusmusson I., Uhlin M., Le B.K., Levitsky V. Mesenchymal stem cells fail to trigger effector functions of cytotoxic T lymphocytes. J Leukoc Biol 2007;82:887-93.</p><p>Da Silva V.L., Chagetelles P.C., Nardi N.B. Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci 2006;119:2204-13.</p><p>Hu Y., Liao L., Wang O. et al. Isolation and identification of mesenchymal stem cells from human fetal pancreas J Lab Clin Med 2003;141:342-9.</p><p>Romanov Y.A., Svintitskaya V.A., Smirnov V.N. Seaching for alternative sources of potential human mesenchymal stem cells: candidate VSC-like cells from umbilical cord. Stem Cells 2003;21:105-10.</p><p>Hu Y., Liao L., Wang O. et al. Isolation and identification of mesenchymal stem cells from human fetal pancreas. J Lab Clin Med 2003;141:342-9.</p><p>Wexler S.A., Donaldson C., Denning-Kendall P. et al. Adult bone marrow is a rich source of human mesenchymal “stem” cells but umbilical cord and mobilized adult blood are not. Br J Haematol 2003;121:368-74.</p><p>Sun L., Aklyama K., Zhang H. et al. Mesenchymal stem cell transplantation reserves multiorgan dysfunction in systemic lupus erythematosus mice and humans. Stem Cells 2009;27:1421-32.</p><p>Ortiz L.A., Dutreil M., Fattman C. Interleukin1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. PNAS USA 2007;104:11002-7.</p><p>Curley G.F., Hayes M., Ansari B. et al. Mesenchymal stem cell enhance recovery and repair following ventilator-induced lung injury in the rat. Thorax 2012;67:496-501.</p><p>Kajstura J., Rota M., Hall S.R., Hosoda T. Evidence for human lung stem cells. N Engl J Med 2011;364:1795-806.</p><p>Шумаков В.М., Онищенко Н.А., Крашенинников М.Е. и др. Экспериментальное обоснование эффективности применения стволовых и прогениторных клеток костного мозга для регуляции восстановительных процессов в органах при остром и хроническом повреждениях. Вестн РАМН 2004;9:44-7.</p><p>Расулов М.Ф., Васильченков А.В., Онищенко Н.А. и др. Первый опыт применения мезенхимальных стромальных клеток костного мозга для лечения больной с глубокими ожоговыми ранами кожи. Клеточн технол в биол и мед 2005;1:42-6.</p><p>Martin I., Baldomero H., Bocelo-Tyndall C. et al. A survey on cell and engineered tissue therapies in Europe in 2010. Tissue Eng Part A, 2012 Jul 19 [Epub. ahead of print].</p><p>Sun L., Wang D., Liang J. et al. Umbilical cord mesenchymal stem cell transplantation in severe and refractory Systemic Lupus Erythematosus. Arthr Rheum 2010;8:2467-75.</p><p>Liang J., Gu F., Wang H. et al. Mesenchymal stem cell transplantation for diffuse alveolar hemorrhage in SLE. Nat Rew Rheumatol 2010;6:486-9.</p><p>Liang J., Zhang H., Hua B. et al. Allogenic mesenchymal stem cells transplantation in refractory systemic lupus erythematosus: a pilot clinical study. Ann Rheum Dis 2010;69:1423-9.</p><p>Carrion F., Nova E., Ruiz C. et.al. Autologous mesenchymal stem cell treatment increased T-regulatory cells with no effect on disease activity in two systemic lupus erythematosus patients. Lupus 2010;19:317-22.</p><p>Larghero J., Farge D., Braccini A. et al. Phenotypical and functional characteristics of in vitro expanded bone marrow mesenchymal stem cell from patients with systemic sclerosis. Ann Rheum Dis 2008;67:443-9.</p><p>Cipriani P., Guiducci S., Miniati I. et al. Impairment of endothelial cell differentiation from bone bone marrow-derived mesenchymal stem cells: new insight into the pathogenesis of systemic sclerosis. Arthr Rheum 2007;56:1994-2004.</p><p>Del Papa N., Quirici N., Soligo D. et al. Bone marrow endothelial progenitors are defective in systemic sclerosis. Arthr Rheum 2006;54:2605-15.</p><p>Christopeit M., Schendel M., Foll J. et al. Marked improvement of severe progressive systemic sclerosis after transplantation of mesenchymal stem cells from allogenic haploidentic al-related donor mediated by ligation of CD 137L. Leukеmia 2008;22:1062-4.</p><p>Keyszer G., Christopeit M., Fick S. et al. Treatment of severe progressive systemic sclerosis with transplantation of mesenchymal stromal cells from allogenic related donors: report of five cases. Arthr Rheum 2011;63:2540-2.</p><p>Wakitani S., Imoto R., Yamamoto T. et al. Human autologous culture expanded bone marrow mesenchymal stem cell transplantaton for repair of cartilage defect in osteoarthritic knees. Osteoarthr Cart 2002;10:199-206.</p><p>Emadedin M., Aqhdami N., Taghiyar L. et al. Intra-articular injection of autologous mesenchymal stem cells in six patients with knee osteoarthritis. Arch Iran Med 2012;15:422-8.</p><p>Meretoja V.V., Dahlin R.L., Kasper F.K., Mikos A.G. Enhanced chondrogenesis in co-cultures with articular chondrocytes and mesenchymal stem cells. Biomaterials 2012; Jun 11 [Epub. ahead of print].</p><p>Gonzales-Rey E., Gonzalez M.A., Varela N. еt al. Human adipose-derived mesenchymal stem cells induce inflammatory and T-cells responses and induce regulatory T-cells in vitro in rheumatoid arthritis. Ann Rheum Dis 2010;69:241-8.</p><p>Liang J., Li X., Zhang H. et al. Allogeneic mesenchymal stem cells transplantation in patients with refractory RA. Clin Rheumatol 2012;31:157-61.</p><p>MacDonald G.I.A., Augello A., de Bari C. Role of mesenchymal stem cells in re-establishing immunological tolerance in autoimmune rheumatic diseases. Arthr Rheum 2011;63:2547-57.</p><p>Zhou Y.F., Bosch-Marce M., Okuyama Y. et al. Spontaneous transformation of cultured mouse bone marrow-derived stromal cells. Cancer Res 2006;66:10849-54.</p><p>Григорян А.С., Кругляков П.В. Спонтанная злокачественная трансформация мультипотентных мезенхимальных стромальных клеток в культуре происходит ли она в действительности? Клеточн трансплантол тканев инженер 2009;4(IV):78-82.</p><p>Bernardo V.E., Zaffaroni N., Novara F. et al. Human bone marrow derived mesenchymal stem cells do not undergo transformation after long-term in vitro culture and do not exibit telomere maintenance mechanisms. Cancer Res 2007;67:9142-9.</p><p>Meza-Zereda L.A., Noer A., Dahl A. et al. High-resolution analysis of genetic stability of human adipose tissue stem cells cultured to senescence. J Cell Mol Med 2008;12:553-63.</p><p>Rubio D., Garcia-Castro J., Martin M.C. et al. Spontaneous human adult stem cells transformation. Cancer Res 2005;65:3035-9.</p><p>Wang Y., Huso D.L., Harrington J. et al. Outgrowth of a transformed cell population derived from normal human BM mesenchymal stem cell culture. Cytotherapy 2005;7:509-19.</p><p>Rosland G.V., Svendsen A., Torsvik A. et al. Long-term cultures of bone marrow-derived human mesenchymal stem cells frequently undergo spontaneous malignant transformation. Cancer Res 2009;69:5331-9.</p><p>Torsvik A., Rosland G.V., Svendsen A. et al. Spontaneous malignant transformation of human mesemchymal stem cells reflects cross-contamination: putting the search field on track letter. Cancer Res 2010;70:6393-6.</p><p>Feinberg A.P., Ohlsson R., Henikoff S. The epigenetic progenitor prigin of human cancer. Nat Rev Gen 2006;7:21-33.</p><p>Centeno C.J., Schultz J.R., Cheever M. et al. Safety and compliations reporting on the reimplantation of culture-expanded mesenchymal stem cells usinf autologous platelet lysate technique. Curr Stem Cell Res Ther 2010;5:81-93.</p><p>Karia V.R., Cuchacovich R., Espinoza L.R. Undifferentiated spondyloarthritis following allogenic stem cel transplantation. Muscolosceletal Dis 2010;11:132-4.</p></div><br /><div><p>Tyndall A. Successes and failures of stem cell transplantation in autoimmune diseases. Hematology Am Soc Hematol Educ Program 2011;2011:280-4.</p><p>Chen Y., Shao J.Z., Xiang L.X. et.al. Mesenchymal stem cell: a promising candidate in regenerative medicine. Int J Biochem Cell Biol 2008;40:815-20.</p><p>Müller I., Lymperi S., Dazzi T. Mesenchymal stem cell therapy for degenerative inflammatory disoders. Curr Opin Organ Transplant 2008;13:639-44.</p><p>Friedenstein A.J., Petrakova K.V., Kurolesova A.I., Frolova G.P. Heterotopic of bone marrow. Analysis of precursor cells for octeogenic and hematopoetic tissue. Transplantation 1968;6:230-47.</p><p>Roberts S., Genever P., McCaski A., De Bari C. Prospects of stem cell therapy in osteoarthritis. Regen Med 2011;6:351-66.</p><p>Prockop D.J. Marrow stromal cells as stem cells for non-hematopoetic tissues. Science 1997;278:71-4</p><p>Domimici M., Le Blank K., Mueller I. et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006;8:315-7.</p><p>Pittenger M.F., Mackay A.M., Beck S.C. et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999;284:143-7.</p><p>Horwitz E., Le Blanc К., Dominici M. et al. Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy 2005;7:393-5.</p><p>Rasmusson I. Immune modulation by mesenchymal stem cells. Exp Cell Res 2006;312:2169-79.</p><p>Le Blanc K., Tammik C., Rosendahl K. et al. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol 2003;31:890-6.</p><p>Majumdar M.К., Keane-Moore M., Buyaner D. et al. Characterization and functionality of cell surface molecules on human mesenchymal stem cells. J Biomed Sci 2003;10:228-41.</p><p>Schwartz R.H. A cell culture model for T lymphocyte clonal anergy. Science 1990;248:1349-56.</p><p>Nauta A.J., Fibbe W.E. Immunomodulatory properties of mesenchymal stromal cells. Blood 2007;110:3499-506.</p><p>Corcione A., Benvenuto F., Ferretti E. et al. Human mesenchymal stem cell modulate B-cells functions. Blood 2006;107:367-72.</p><p>Honczarenko M., Le Y., Swierkowski M. et al. Human BMSC express a distinct set of biologically functional chemokine receptors. Stem Cells 2006;24:1030-41.</p><p>DelaRosa O., Lombardo E., Beraza A. et al. Requirement of INF-gamma-mediated indoleamine 2,3-dioxigenase expression in the modulation of lymphocyte proliferation by human adipose-derived stem cells. Tissue Eng 2009;15:2795-806.</p><p>Zappia E., Casazza S., Pedemonte E. et al. Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis indusing T-cell anergy. Blood 2005;106:1755-61.</p><p>Sheng H., Wang Y., Jin Y et al. A critical role of INF in priming MSC-mediated supression of T cell proliferation through up-regulation of B7-H1. Cell Res 2008;18:846-57.</p><p>Di Nicola M., Carlo-Stella C., Magni M. et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 2002;99:3838-43.</p><p>English K., Ryan J.M., Tobin L. et al. Cell contact, prostaglandin E(2) and transforming growth factor beta 1 play non-redundant roles in human mesenchymal stem cell induction of CD4+CD25 (High) forkhead box P3+ regulatory T-cells. Clin Exp Immunol 2009;156:149-60.</p><p>Yang S.H., Park M.J., Yoon I.H. et al. Soluble mediators from mesenchymal stem cell suppress T-cell proliferation by inducing IL-10. Exp Mol Med 2009;41:315-24.</p><p>Sato K., Ozaki K., Oh I. et al. Nitric oxide plays a critical role in supression of T-cell proliferation by mesenchymal stem cells. Blood 2007;109:228-34.</p><p>Ren G., Zhang L., Zhao X. et al. Mesenchymal stem cell-mediated immunosupression occurs via cjncerted action of chemokines and nitric oxide. Cell Stem Cell 2008;2:141-50.</p><p>Rusmusson I., Uhlin M., Le B.K., Levitsky V. Mesenchymal stem cells fail to trigger effector functions of cytotoxic T lymphocytes. J Leukoc Biol 2007;82:887-93.</p><p>Da Silva V.L., Chagetelles P.C., Nardi N.B. Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci 2006;119:2204-13.</p><p>Hu Y., Liao L., Wang O. et al. Isolation and identification of mesenchymal stem cells from human fetal pancreas J Lab Clin Med 2003;141:342-9.</p><p>Romanov Y.A., Svintitskaya V.A., Smirnov V.N. Seaching for alternative sources of potential human mesenchymal stem cells: candidate VSC-like cells from umbilical cord. Stem Cells 2003;21:105-10.</p><p>Hu Y., Liao L., Wang O. et al. Isolation and identification of mesenchymal stem cells from human fetal pancreas. J Lab Clin Med 2003;141:342-9.</p><p>Wexler S.A., Donaldson C., Denning-Kendall P. et al. Adult bone marrow is a rich source of human mesenchymal “stem” cells but umbilical cord and mobilized adult blood are not. Br J Haematol 2003;121:368-74.</p><p>Sun L., Aklyama K., Zhang H. et al. Mesenchymal stem cell transplantation reserves multiorgan dysfunction in systemic lupus erythematosus mice and humans. Stem Cells 2009;27:1421-32.</p><p>Ortiz L.A., Dutreil M., Fattman C. Interleukin1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. PNAS USA 2007;104:11002-7.</p><p>Curley G.F., Hayes M., Ansari B. et al. Mesenchymal stem cell enhance recovery and repair following ventilator-induced lung injury in the rat. Thorax 2012;67:496-501.</p><p>Kajstura J., Rota M., Hall S.R., Hosoda T. Evidence for human lung stem cells. N Engl J Med 2011;364:1795-806.</p><p>Шумаков В.М., Онищенко Н.А., Крашенинников М.Е. и др. Экспериментальное обоснование эффективности применения стволовых и прогениторных клеток костного мозга для регуляции восстановительных процессов в органах при остром и хроническом повреждениях. Вестн РАМН 2004;9:44-7.</p><p>Расулов М.Ф., Васильченков А.В., Онищенко Н.А. и др. Первый опыт применения мезенхимальных стромальных клеток костного мозга для лечения больной с глубокими ожоговыми ранами кожи. Клеточн технол в биол и мед 2005;1:42-6.</p><p>Martin I., Baldomero H., Bocelo-Tyndall C. et al. A survey on cell and engineered tissue therapies in Europe in 2010. Tissue Eng Part A, 2012 Jul 19 [Epub. ahead of print].</p><p>Sun L., Wang D., Liang J. et al. Umbilical cord mesenchymal stem cell transplantation in severe and refractory Systemic Lupus Erythematosus. Arthr Rheum 2010;8:2467-75.</p><p>Liang J., Gu F., Wang H. et al. Mesenchymal stem cell transplantation for diffuse alveolar hemorrhage in SLE. Nat Rew Rheumatol 2010;6:486-9.</p><p>Liang J., Zhang H., Hua B. et al. Allogenic mesenchymal stem cells transplantation in refractory systemic lupus erythematosus: a pilot clinical study. Ann Rheum Dis 2010;69:1423-9.</p><p>Carrion F., Nova E., Ruiz C. et.al. Autologous mesenchymal stem cell treatment increased T-regulatory cells with no effect on disease activity in two systemic lupus erythematosus patients. Lupus 2010;19:317-22.</p><p>Larghero J., Farge D., Braccini A. et al. Phenotypical and functional characteristics of in vitro expanded bone marrow mesenchymal stem cell from patients with systemic sclerosis. Ann Rheum Dis 2008;67:443-9.</p><p>Cipriani P., Guiducci S., Miniati I. et al. Impairment of endothelial cell differentiation from bone bone marrow-derived mesenchymal stem cells: new insight into the pathogenesis of systemic sclerosis. Arthr Rheum 2007;56:1994-2004.</p><p>Del Papa N., Quirici N., Soligo D. et al. Bone marrow endothelial progenitors are defective in systemic sclerosis. Arthr Rheum 2006;54:2605-15.</p><p>Christopeit M., Schendel M., Foll J. et al. Marked improvement of severe progressive systemic sclerosis after transplantation of mesenchymal stem cells from allogenic haploidentic al-related donor mediated by ligation of CD 137L. Leukеmia 2008;22:1062-4.</p><p>Keyszer G., Christopeit M., Fick S. et al. Treatment of severe progressive systemic sclerosis with transplantation of mesenchymal stromal cells from allogenic related donors: report of five cases. Arthr Rheum 2011;63:2540-2.</p><p>Wakitani S., Imoto R., Yamamoto T. et al. Human autologous culture expanded bone marrow mesenchymal stem cell transplantaton for repair of cartilage defect in osteoarthritic knees. Osteoarthr Cart 2002;10:199-206.</p><p>Emadedin M., Aqhdami N., Taghiyar L. et al. Intra-articular injection of autologous mesenchymal stem cells in six patients with knee osteoarthritis. Arch Iran Med 2012;15:422-8.</p><p>Meretoja V.V., Dahlin R.L., Kasper F.K., Mikos A.G. Enhanced chondrogenesis in co-cultures with articular chondrocytes and mesenchymal stem cells. Biomaterials 2012; Jun 11 [Epub. ahead of print].</p><p>Gonzales-Rey E., Gonzalez M.A., Varela N. еt al. Human adipose-derived mesenchymal stem cells induce inflammatory and T-cells responses and induce regulatory T-cells in vitro in rheumatoid arthritis. Ann Rheum Dis 2010;69:241-8.</p><p>Liang J., Li X., Zhang H. et al. Allogeneic mesenchymal stem cells transplantation in patients with refractory RA. Clin Rheumatol 2012;31:157-61.</p><p>MacDonald G.I.A., Augello A., de Bari C. Role of mesenchymal stem cells in re-establishing immunological tolerance in autoimmune rheumatic diseases. Arthr Rheum 2011;63:2547-57.</p><p>Zhou Y.F., Bosch-Marce M., Okuyama Y. et al. Spontaneous transformation of cultured mouse bone marrow-derived stromal cells. Cancer Res 2006;66:10849-54.</p><p>Григорян А.С., Кругляков П.В. Спонтанная злокачественная трансформация мультипотентных мезенхимальных стромальных клеток в культуре происходит ли она в действительности? Клеточн трансплантол тканев инженер 2009;4(IV):78-82.</p><p>Bernardo V.E., Zaffaroni N., Novara F. et al. Human bone marrow derived mesenchymal stem cells do not undergo transformation after long-term in vitro culture and do not exibit telomere maintenance mechanisms. Cancer Res 2007;67:9142-9.</p><p>Meza-Zereda L.A., Noer A., Dahl A. et al. High-resolution analysis of genetic stability of human adipose tissue stem cells cultured to senescence. J Cell Mol Med 2008;12:553-63.</p><p>Rubio D., Garcia-Castro J., Martin M.C. et al. Spontaneous human adult stem cells transformation. Cancer Res 2005;65:3035-9.</p><p>Wang Y., Huso D.L., Harrington J. et al. Outgrowth of a transformed cell population derived from normal human BM mesenchymal stem cell culture. Cytotherapy 2005;7:509-19.</p><p>Rosland G.V., Svendsen A., Torsvik A. et al. Long-term cultures of bone marrow-derived human mesenchymal stem cells frequently undergo spontaneous malignant transformation. Cancer Res 2009;69:5331-9.</p><p>Torsvik A., Rosland G.V., Svendsen A. et al. Spontaneous malignant transformation of human mesemchymal stem cells reflects cross-contamination: putting the search field on track letter. Cancer Res 2010;70:6393-6.</p><p>Feinberg A.P., Ohlsson R., Henikoff S. The epigenetic progenitor prigin of human cancer. Nat Rev Gen 2006;7:21-33.</p><p>Centeno C.J., Schultz J.R., Cheever M. et al. Safety and compliations reporting on the reimplantation of culture-expanded mesenchymal stem cells usinf autologous platelet lysate technique. Curr Stem Cell Res Ther 2010;5:81-93.</p><p>Karia V.R., Cuchacovich R., Espinoza L.R. Undifferentiated spondyloarthritis following allogenic stem cel transplantation. Muscolosceletal Dis 2010;11:132-4.</p></div><br />

The authors declare that there are no conflicts of interest present.