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Mesenchymal stromal cells for cell therapy: besides supporting hematopoiesis

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Abstract

Mesenchymal stromal cells (MSC) have attracted the attention of scientists and clinicians due to their self-renewal, capacity for multipotent differentiation, and immunomodulatory properties. Some essential problems remain to be solved before the clinical application of MSC. Platelet lysate (PL) has recently been used as a substitute for FBS in MSC amplification in vitro to achieve clinically applicable numbers of MSC. In addition to promising trials in regenerative medicine, such as in the treatment of major bone defects and myocardial infarction, MSC have shown therapeutic effect other than direct hematopoiesis support in hematopoietic reconstruction. It has been confirmed that MSC promote hematopoietic cell engraftment and immune recovery after allogeneic hematopoietic stem cell transplantation, probably through the provision of cytokines, matrix proteins, and cell-to-cell contacts. Their suppressive effects on immune cells, including T cells, B cells, NK cells and DC cells, suggest MSCs as a novel therapy for GVHD and other autoimmune disorders. These cells thus present as promising candidates for cellular therapy in the fields of regenerative medicine, allogeneic hematopoietic stem cell transplantation, and autoimmune disorders.

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References

  1. Beyer Nardi N, da Silva Meirelles L. Mesenchymal stem cells: isolation, in vitro expansion and characterization. Handb Exp Pharmacol. 2006;(174):249.

  2. Bianco P, Gehron Robey P. Marrow stromal stem cells. J Clin Invest. 2000;105(12):1663.

    Article  PubMed  CAS  Google Scholar 

  3. Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science. 1997;276(5309):71.

    Article  PubMed  CAS  Google Scholar 

  4. Sethe S, Scutt A, Stolzing A. Aging of mesenchymal stem cells. Ageing Res Rev. 2006;5(1):91.

    Article  PubMed  CAS  Google Scholar 

  5. Campagnoli C, Roberts IA, Kumar S, Bennett PR, Bellantuono I, Fisk NM. Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood. 2001;98(8):2396.

    Article  PubMed  CAS  Google Scholar 

  6. Igura K, Zhang X, Takahashi K, Mitsuru A, Yamaguchi S, Takashi TA. Isolation and characterization of mesenchymal progenitor cells from chorionic villi of human placenta. Cytotherapy. 2004;6(6):543.

    Article  PubMed  CAS  Google Scholar 

  7. Tsai MS, Lee JL, Chang YJ, Hwang SM. Isolation of human multipotent mesenchymal stem cells from second-trimester amniotic fluid using a novel two-stage culture protocol. Hum Reprod. 2004;19(6):1450.

    Article  PubMed  Google Scholar 

  8. Kern S, Eichler H, Stoeve J, Kluter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells. 2006;24(5):1294.

    Article  PubMed  CAS  Google Scholar 

  9. Toma C, Pittenger MF, Cahill KS, Byrne BJ, Kessler PD. Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation. 2002;105(1):93.

    Article  PubMed  Google Scholar 

  10. Pittenger MF, Martin BJ. Mesenchymal stem cells and their potential as cardiac therapeutics. Circ Res. 2004;95(1):9.

    Article  PubMed  CAS  Google Scholar 

  11. Kopen GC, Prockop DJ, Phinney DG. Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc Natl Acad Sci USA. 1999;96(19):10711.

    Article  PubMed  CAS  Google Scholar 

  12. Woodbury D, Schwarz EJ, Prockop DJ, Black IB. Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res. 2000;61(4):364.

    Article  PubMed  CAS  Google Scholar 

  13. Reyes M, Dudek A, Jahagirdar B, Koodie L, Marker PH, Verfaillie CM. Origin of endothelial progenitors in human postnatal bone marrow. J Clin Invest. 2002;109(3):337.

    PubMed  CAS  Google Scholar 

  14. Sato Y, Araki H, Kato J, et al. Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion. Blood. 2005;106(2):756.

    Article  PubMed  CAS  Google Scholar 

  15. Anjos-Afonso F, Bonnet D. Nonhematopoietic/endothelial SSEA-1+ cells define the most primitive progenitors in the adult murine bone marrow mesenchymal compartment. Blood. 2007;109(3):1298.

    Article  PubMed  CAS  Google Scholar 

  16. Buhring HJ, Battula VL, Treml S, Schewe B, Kanz L, Vogel W. Novel markers for the prospective isolation of human MSC. Ann N Y Acad Sci. 2007;1106:262.

    Article  PubMed  CAS  Google Scholar 

  17. Gang EJ, Bosnakovski D, Figueiredo CA, Visser JW, Perlingeiro RC. SSEA-4 identifies mesenchymal stem cells from bone marrow. Blood. 2007;109(4):1743.

    Article  PubMed  CAS  Google Scholar 

  18. Quirici N, Soligo D, Bossolasco P, Servida F, Lumini C, Deliliers GL. Isolation of bone marrow mesenchymal stem cells by anti-nerve growth factor receptor antibodies. Exp Hematol. 2002;30(7):783.

    Article  PubMed  CAS  Google Scholar 

  19. Simmons PJ, Torok-Storb B. Identification of stromal cell precursors in human bone marrow by a novel monoclonal antibody, STRO-1. Blood. 1991;78(1):55.

    PubMed  CAS  Google Scholar 

  20. Battula VL, Treml S, Bareiss PM, et al. Isolation of functionally distinct mesenchymal stem cell subsets using antibodies against CD56, CD271, and mesenchymal stem cell antigen-1. Haematologica. 2009;94(2):173.

    Article  PubMed  CAS  Google Scholar 

  21. Niehage C, Steenblock C, Pursche T, Bornhauser M, Corbeil D, Hoflack B. The cell surface proteome of human mesenchymal stromal cells. PLoS One. 2011;6(5):e20399.

    Article  PubMed  CAS  Google Scholar 

  22. Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315.

    Article  PubMed  CAS  Google Scholar 

  23. Bernardo ME, Cometa AM, Pagliara D, et al. Ex vivo expansion of mesenchymal stromal cells. Best Pract Res Clin Haematol. 2011;24(1):73.

    Article  PubMed  CAS  Google Scholar 

  24. Devine SM, Cobbs C, Jennings M, Bartholomew A, Hoffman R. Mesenchymal stem cells distribute to a wide range of tissues following systemic infusion into nonhuman primates. Blood. 2003;101(8):2999.

    Article  PubMed  CAS  Google Scholar 

  25. Bernardo ME, Locatelli F, Fibbe WE. Mesenchymal stromal cells. Ann N Y Acad Sci. 2009;1176:101.

    Article  PubMed  CAS  Google Scholar 

  26. Bianco P, Costantini M, Dearden LC, Bonucci E. Alkaline phosphatase positive precursors of adipocytes in the human bone marrow. Br J Haematol. 1988;68(4):401.

    Article  PubMed  CAS  Google Scholar 

  27. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284(5411):143.

    Article  PubMed  CAS  Google Scholar 

  28. Jiang Y, Jahagirdar BN, Reinhardt RL, et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature. 2002;418(6893):41.

    Article  PubMed  CAS  Google Scholar 

  29. Tavassoli M, Friedenstein A. Hemopoietic stromal microenvironment. Am J Hematol. 1983;15(2):195.

    Article  PubMed  CAS  Google Scholar 

  30. Suniara RK, Jenkinson EJ, Owen JJ. An essential role for thymic mesenchyme in early T cell development. J Exp Med. 2000;191(6):1051.

    Article  PubMed  CAS  Google Scholar 

  31. Bartholomew A, Sturgeon C, Siatskas M, et al. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol. 2002;30(1):42.

    Article  PubMed  Google Scholar 

  32. 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(10):3838.

    Article  PubMed  CAS  Google Scholar 

  33. Tse WT, Pendleton JD, Beyer WM, Egalka MC, Guinan EC. Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation. 2003;75(3):389.

    Article  PubMed  CAS  Google Scholar 

  34. Krampera M, Glennie S, Dyson J, et al. Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood. 2003;101(9):3722.

    Article  PubMed  CAS  Google Scholar 

  35. Le Blanc K, Ringden O. Immunomodulation by mesenchymal stem cells and clinical experience. J Intern Med. 2007;262(5):509.

    Article  PubMed  CAS  Google Scholar 

  36. Corcione A, Benvenuto F, Ferretti E, et al. Human mesenchymal stem cells modulate B-cell functions. Blood. 2006;107(1):367.

    Article  PubMed  CAS  Google Scholar 

  37. Spaggiari GM, Capobianco A, Becchetti S, Mingari MC, Moretta L. Mesenchymal stem cell–natural killer cell interactions: evidence that activated NK cells are capable of killing MSCs, whereas MSCs can inhibit IL-2-induced NK-cell proliferation. Blood. 2006;107(4):1484.

    Article  PubMed  CAS  Google Scholar 

  38. Sotiropoulou PA, Perez SA, Gritzapis AD, Baxevanis CN, Papamichail M. Interactions between human mesenchymal stem cells and natural killer cells. Stem Cells. 2006;24(1):74.

    Article  PubMed  Google Scholar 

  39. Nauta AJ, Kruisselbrink AB, Lurvink E, Willemze R, Fibbe WE. Mesenchymal stem cells inhibit generation and function of both CD34+-derived and monocyte-derived dendritic cells. J Immunol. 2006;177(4):2080.

    PubMed  CAS  Google Scholar 

  40. Beyth S, Borovsky Z, Mevorach D, et al. Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness. Blood. 2005;105(5):2214.

    Article  PubMed  CAS  Google Scholar 

  41. Pieri L, Urbani S, Mazzanti B, et al. Human mesenchymal stromal cells preserve their stem features better when cultured in the Dulbecco’s modified Eagle medium. Cytotherapy. 2011;13(5):539.

    Article  PubMed  CAS  Google Scholar 

  42. Selvaggi TA, Walker RE, Fleisher TA. Development of antibodies to fetal calf serum with arthus-like reactions in human immunodeficiency virus-infected patients given syngeneic lymphocyte infusions. Blood. 1997;89(3):776.

    PubMed  CAS  Google Scholar 

  43. Tuschong L, Soenen SL, Blaese RM, Candotti F, Muul LM. Immune response to fetal calf serum by two adenosine deaminase-deficient patients after T cell gene therapy. Hum Gene Ther. 2002;13(13):1605.

    Article  PubMed  CAS  Google Scholar 

  44. Even MS, Sandusky CB, Barnard ND. Serum-free hybridoma culture: ethical, scientific and safety considerations. Trends Biotechnol. 2006;24(3):105.

    Article  PubMed  CAS  Google Scholar 

  45. Felka T, Schafer R, De Zwart P, Aicher WK. Animal serum-free expansion and differentiation of human mesenchymal stromal cells. Cytotherapy. 2010;12(2):143.

    Article  PubMed  CAS  Google Scholar 

  46. Stute N, Holtz K, Bubenheim M, Lange C, Blake F, Zander AR. Autologous serum for isolation and expansion of human mesenchymal stem cells for clinical use. Exp Hematol. 2004;32(12):1212.

    Article  PubMed  CAS  Google Scholar 

  47. Shahdadfar A, Fronsdal K, Haug T, Reinholt FP, Brinchmann JE. In vitro expansion of human mesenchymal stem cells: choice of serum is a determinant of cell proliferation, differentiation, gene expression, and transcriptome stability. Stem Cells. 2005;23(9):1357.

    Article  PubMed  CAS  Google Scholar 

  48. Mizuno N, Shiba H, Ozeki Y, et al. Human autologous serum obtained using a completely closed bag system as a substitute for foetal calf serum in human mesenchymal stem cell cultures. Cell Biol Int. 2006;30(6):521.

    Article  PubMed  CAS  Google Scholar 

  49. Spees JL, Gregory CA, Singh H, et al. Internalized antigens must be removed to prepare hypoimmunogenic mesenchymal stem cells for cell and gene therapy. Mol Ther. 2004;9(5):747.

    Article  PubMed  CAS  Google Scholar 

  50. Lange C, Cakiroglu F, Spiess AN, Cappallo-Obermann H, Dierlamm J, Zander AR. Accelerated and safe expansion of human mesenchymal stromal cells in animal serum-free medium for transplantation and regenerative medicine. J Cell Physiol. 2007;213(1):18.

    Article  PubMed  CAS  Google Scholar 

  51. Hatlapatka T, Moretti P, Lavrentieva A, et al. Optimization of culture conditions for the expansion of umbilical cord-derived mesenchymal stem or stromal cell-like cells using xeno-free culture conditions. Tissue Eng Part C Methods. 2011;17(4):485.

    Article  PubMed  Google Scholar 

  52. Shih DT, Chen JC, Chen WY, Kuo YP, Su CY, Burnouf T. Expansion of adipose tissue mesenchymal stromal progenitors in serum-free medium supplemented with virally inactivated allogeneic human platelet lysate. Transfusion. 2011;51(4):770.

    Article  PubMed  Google Scholar 

  53. Cholewa D, Stiehl T, Schellenberg A, et al. Expansion of adipose mesenchymal stromal cells is affected by human platelet lysate and plating density. Cell Transplant. 2011;20(9):1409–22.

    Article  PubMed  Google Scholar 

  54. Capelli C, Gotti E, Morigi M, et al. Minimally manipulated whole human umbilical cord is a rich source of clinical-grade human mesenchymal stromal cells expanded in human platelet lysate. Cytotherapy. 2011;13(7):786.

    Article  PubMed  CAS  Google Scholar 

  55. Horn P, Bokermann G, Cholewa D, et al. Impact of individual platelet lysates on isolation and growth of human mesenchymal stromal cells. Cytotherapy. 2010;12(7):888.

    Article  PubMed  CAS  Google Scholar 

  56. Schallmoser K, Rohde E, Bartmann C, Obenauf AC, Reinisch A, Strunk D. Platelet-derived growth factors for GMP-compliant propagation of mesenchymal stromal cells. Biomed Mater Eng. 2009;19(4–5):271.

    PubMed  Google Scholar 

  57. von Bonin M, Stolzel F, Goedecke A, et al. Treatment of refractory acute GVHD with third-party MSC expanded in platelet lysate-containing medium. Bone Marrow Transplant. 2009;43(3):245.

    Article  CAS  Google Scholar 

  58. Jung J, Moon N, Ahn JY, et al. Mesenchymal stromal cells expanded in human allogenic cord blood serum display higher self-renewal and enhanced osteogenic potential. Stem Cells Dev. 2009;18(4):559.

    Article  PubMed  CAS  Google Scholar 

  59. Jung S, Sen A, Rosenberg L, Behie LA. Identification of growth and attachment factors for the serum-free isolation and expansion of human mesenchymal stromal cells. Cytotherapy. 2010;12(5):637.

    Article  PubMed  CAS  Google Scholar 

  60. Chase LG, Lakshmipathy U, Solchaga LA, Rao MS, Vemuri MC. A novel serum-free medium for the expansion of human mesenchymal stem cells. Stem Cell Res Ther. 2010;1(1):8.

    Article  PubMed  CAS  Google Scholar 

  61. Montzka K, Fuhrmann T, Woltje M, Brook GA. Expansion of human bone marrow-derived mesenchymal stromal cells: serum-reduced medium is better than conventional medium. Cytotherapy. 2010;12(5):587.

    Article  PubMed  CAS  Google Scholar 

  62. Oskowitz A, McFerrin H, Gutschow M, Carter ML, Pochampally R. Serum-deprived human multipotent mesenchymal stromal cells (MSCs) are highly angiogenic. Stem Cell Res. 2011;6(3):215.

    Article  PubMed  CAS  Google Scholar 

  63. Miura M, Miura Y, Padilla-Nash HM, et al. Accumulated chromosomal instability in murine bone marrow mesenchymal stem cells leads to malignant transformation. Stem Cells. 2006;24(4):1095.

    Article  PubMed  Google Scholar 

  64. Aguilar S, Nye E, Chan J, et al. Murine but not human mesenchymal stem cells generate osteosarcoma-like lesions in the lung. Stem Cells. 2007;25(6):1586.

    Article  PubMed  Google Scholar 

  65. Tolar J, Nauta AJ, Osborn MJ, et al. Sarcoma derived from cultured mesenchymal stem cells. Stem Cells. 2007;25(2):371.

    Article  PubMed  CAS  Google Scholar 

  66. Prockop DJ, Brenner M, Fibbe WE, et al. Defining the risks of mesenchymal stromal cell therapy. Cytotherapy. 2010;12(5):576.

    Article  PubMed  Google Scholar 

  67. Izadpanah R, Kaushal D, Kriedt C, et al. Long-term in vitro expansion alters the biology of adult mesenchymal stem cells. Cancer Res. 2008;68(11):4229.

    Article  PubMed  CAS  Google Scholar 

  68. Vilalta M, Degano IR, Bago J, et al. Biodistribution, long-term survival, and safety of human adipose tissue-derived mesenchymal stem cells transplanted in nude mice by high sensitivity non-invasive bioluminescence imaging. Stem Cells Dev. 2008;17(5):993.

    Article  PubMed  Google Scholar 

  69. Bieback K, Hecker A, Kocaomer A, et al. Human alternatives to fetal bovine serum for the expansion of mesenchymal stromal cells from bone marrow. Stem Cells. 2009;27(9):2331.

    Article  PubMed  CAS  Google Scholar 

  70. Rubio D, Garcia S, De la Cueva T, et al. Human mesenchymal stem cell transformation is associated with a mesenchymal–epithelial transition. Exp Cell Res. 2008;314(4):691.

    Article  PubMed  CAS  Google Scholar 

  71. Garcia S, Bernad A, Martin MC, Cigudosa JC, Garcia-Castro J, de la Fuente R. Pitfalls in spontaneous in vitro transformation of human mesenchymal stem cells. Exp Cell Res. 2010;316(9):1648.

    Google Scholar 

  72. Tarte K, Gaillard J, Lataillade JJ, et al. Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformation. Blood. 2010;115(8):1549.

    Google Scholar 

  73. Liu G, Shu C, Cui L, Liu W, Cao Y. Tissue-engineered bone formation with cryopreserved human bone marrow mesenchymal stem cells. Cryobiology. 2008;56(3):209.

    Article  PubMed  CAS  Google Scholar 

  74. Casado-Diaz A, Santiago-Mora R, Jimenez R, et al. Cryopreserved human bone marrow mononuclear cells as a source of mesenchymal stromal cells: application in osteoporosis research. Cytotherapy. 2008;10(5):460.

    Article  PubMed  CAS  Google Scholar 

  75. Gonda K, Shigeura T, Sato T, et al. Preserved proliferative capacity and multipotency of human adipose-derived stem cells after long-term cryopreservation. Plast Reconstr Surg. 2008;121(2):401.

    Article  PubMed  CAS  Google Scholar 

  76. Haack-Sorensen M, Bindslev L, Mortensen S, Friis T, Kastrup J. The influence of freezing and storage on the characteristics and functions of human mesenchymal stromal cells isolated for clinical use. Cytotherapy. 2007;9(4):328.

    Article  PubMed  CAS  Google Scholar 

  77. Zhang HT, Chen H, Zhao H, Dai YW, Xu RX. Neural stem cells differentiation ability of human umbilical cord mesenchymal stromal cells is not altered by cryopreservation. Neurosci Lett. 2011;487(1):118.

    Article  PubMed  CAS  Google Scholar 

  78. Zeisberger SM, Schulz JC, Mairhofer M, et al. Biological and physicochemical characterization of a serum- and xeno-free chemically defined cryopreservation procedure for adult human progenitor cells. Cell Transplant. 2010;20(8):1241.

    Google Scholar 

  79. Bhakta G, Lee KH, Magalhaes R, et al. Cryopreservation of alginate-fibrin beads involving bone marrow derived mesenchymal stromal cells by vitrification. Biomaterials. 2009;30(3):336.

    Article  PubMed  CAS  Google Scholar 

  80. Zhang X, Hirai M, Cantero S, et al. Isolation and characterization of mesenchymal stem cells from human umbilical cord blood: reevaluation of critical factors for successful isolation and high ability to proliferate and differentiate to chondrocytes as compared to mesenchymal stem cells from bone marrow and adipose tissue. J Cell Biochem. 2011;112(4):1206.

    Article  PubMed  CAS  Google Scholar 

  81. Pachon-Pena G, Yu G, Tucker A, et al. Stromal stem cells from adipose tissue and bone marrow of age-matched female donors display distinct immunophenotypic profiles. J Cell Physiol. 2011;226(3):843.

    Article  PubMed  CAS  Google Scholar 

  82. Shafiee A, Seyedjafari E, Soleimani M, Ahmadbeigi N, Dinarvand P, Ghaemi N. A comparison between osteogenic differentiation of human unrestricted somatic stem cells and mesenchymal stem cells from bone marrow and adipose tissue. Biotechnol Lett. 2011;33(6):1257.

    Article  PubMed  CAS  Google Scholar 

  83. Hofmann A, Ritz U, Hessmann MH, et al. Cell viability, osteoblast differentiation, and gene expression are altered in human osteoblasts from hypertrophic fracture non-unions. Bone. 2008;42(5):894.

    Article  PubMed  CAS  Google Scholar 

  84. Seebach C, Henrich D, Tewksbury R, Wilhelm K, Marzi I. Number and proliferative capacity of human mesenchymal stem cells are modulated positively in multiple trauma patients and negatively in atrophic nonunions. Calcif Tissue Int. 2007;80(4):294.

    Article  PubMed  CAS  Google Scholar 

  85. Bruder SP, Kraus KH, Goldberg VM, Kadiyala S. The effect of implants loaded with autologous mesenchymal stem cells on the healing of canine segmental bone defects. J Bone Jt Surg Am. 1998;80(7):985.

    CAS  Google Scholar 

  86. Kon E, Muraglia A, Corsi A, et al. Autologous bone marrow stromal cells loaded onto porous hydroxyapatite ceramic accelerate bone repair in critical-size defects of sheep long bones. J Biomed Mater Res. 2000;49(3):328.

    Article  PubMed  CAS  Google Scholar 

  87. Cancedda R, Dozin B, Giannoni P, Quarto R. Tissue engineering and cell therapy of cartilage and bone. Matrix Biol. 2003;22(1):81.

    Article  PubMed  CAS  Google Scholar 

  88. Giannoni P, Mastrogiacomo M, Alini M, et al. Regeneration of large bone defects in sheep using bone marrow stromal cells. J Tissue Eng Regen Med. 2008;2(5):253.

    Article  PubMed  CAS  Google Scholar 

  89. Petite H, Viateau V, Bensaid W, et al. Tissue-engineered bone regeneration. Nat Biotechnol. 2000;18(9):959.

    Article  PubMed  CAS  Google Scholar 

  90. Salvade A, Della Mina P, Gaddi D, et al. Characterization of platelet lysate cultured mesenchymal stromal cells and their potential use in tissue-engineered osteogenic devices for the treatment of bone defects. Tissue Eng Part C Methods. 2010;16(2):201.

    Google Scholar 

  91. Quarto R, Mastrogiacomo M, Cancedda R, et al. Repair of large bone defects with the use of autologous bone marrow stromal cells. N Engl J Med. 2001;344(5):385.

    Article  PubMed  CAS  Google Scholar 

  92. Marcacci M, Kon E, Moukhachev V, et al. Stem cells associated with macroporous bioceramics for long bone repair: 6- to 7-year outcome of a pilot clinical study. Tissue Eng. 2007;13(5):947.

    Article  PubMed  CAS  Google Scholar 

  93. Srouji S, Ben-David D, Fromigue O, et al. Lentiviral-mediated integrin alpha 5 expression in human adult mesenchymal stromal cells promotes bone repair in mouse cranial and long bone defects. Hum Gene Ther. 2011 [Epub ahead of print].

  94. Scotti C, Tonnarelli B, Papadimitropoulos A, et al. Recapitulation of endochondral bone formation using human adult mesenchymal stem cells as a paradigm for developmental engineering. Proc Natl Acad Sci USA. 2010;107(16):7251.

    Article  PubMed  CAS  Google Scholar 

  95. Makino S, Fukuda K, Miyoshi S, et al. Cardiomyocytes can be generated from marrow stromal cells in vitro. J Clin Invest. 1999;103(5):697.

    Article  PubMed  CAS  Google Scholar 

  96. Wang D, Zhang F, Shen W, et al. Mesenchymal stem cell injection ameliorates the inducibility of ventricular arrhythmias after myocardial infarction in rats. Int J Cardiol. 2011;152(3):314.

    Google Scholar 

  97. Sato T, Iso Y, Uyama T, et al. Coronary vein infusion of multipotent stromal cells from bone marrow preserves cardiac function in swine ischemic cardiomyopathy via enhanced neovascularization. Lab Invest. 2011;91(4):553.

    Google Scholar 

  98. Vela DC, Silva GV, Assad JA, et al. Histopathological study of healing after allogenic mesenchymal stem cell delivery in myocardial infarction in dogs. J Histochem Cytochem. 2009;57(2):167.

    Article  PubMed  CAS  Google Scholar 

  99. Amado LC, Saliaris AP, Schuleri KH, et al. Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction. Proc Natl Acad Sci USA. 2005;102(32):11474.

    Article  PubMed  CAS  Google Scholar 

  100. Barbash IM, Chouraqui P, Baron J, et al. Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium: feasibility, cell migration, and body distribution. Circulation. 2003;108(7):863.

    Article  PubMed  Google Scholar 

  101. Imanishi Y, Saito A, Komoda H, et al. Allogenic mesenchymal stem cell transplantation has a therapeutic effect in acute myocardial infarction in rats. J Mol Cell Cardiol. 2008;44(4):662.

    Article  PubMed  CAS  Google Scholar 

  102. Chan JL, Tang KC, Patel AP, et al. Antigen-presenting property of mesenchymal stem cells occurs during a narrow window at low levels of interferon-gamma. Blood. 2006;107(12):4817.

    Article  PubMed  CAS  Google Scholar 

  103. Schuleri KH, Amado LC, Boyle AJ, et al. Early improvement in cardiac tissue perfusion due to mesenchymal stem cells. Am J Physiol Heart Circ Physiol. 2008;294(5):H2002.

    Article  PubMed  CAS  Google Scholar 

  104. Moscoso I, Barallobre J, de Ilarduya OM, et al. Analysis of different routes of administration of heterologous 5-azacytidine-treated mesenchymal stem cells in a porcine model of myocardial infarction. Transplant Proc. 2009;41(6):2273.

    Article  PubMed  CAS  Google Scholar 

  105. Timmers L, Lim SK, Hoefer IE, et al. Human mesenchymal stem cell-conditioned medium improves cardiac function following myocardial infarction. Stem Cell Res. 2011;6(3):206.

    Google Scholar 

  106. Lai RC, Chen TS, Lim SK. Mesenchymal stem cell exosome: a novel stem cell-based therapy for cardiovascular disease. Regen Med. 2011;6(4):481.

    Google Scholar 

  107. Li Z, Guo J, Chang Q, Zhang A. Paracrine role for mesenchymal stem cells in acute myocardial infarction. Biol Pharm Bull. 2009;32(8):1343.

    Article  PubMed  CAS  Google Scholar 

  108. Hou M, Yang KM, Zhang H, et al. Transplantation of mesenchymal stem cells from human bone marrow improves damaged heart function in rats. Int J Cardiol. 2007;115(2):220.

    Article  PubMed  Google Scholar 

  109. Uemura R, Xu M, Ahmad N, Ashraf M. Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling. Circ Res. 2006;98(11):1414.

    Article  PubMed  CAS  Google Scholar 

  110. Wang Y, Zhang D, Ashraf M, et al. Combining neuropeptide Y and mesenchymal stem cells reverses remodeling after myocardial infarction. Am J Physiol Heart Circ Physiol. 2010;298(1):H275.

    Google Scholar 

  111. Lian WS, Cheng WT, Cheng CC, et al. In vivo therapy of myocardial infarction with mesenchymal stem cells modified with prostaglandin I synthase gene improves cardiac performance in mice. Life Sci. 2011;88(9–10):455.

    Google Scholar 

  112. Deuse T, Peter C, Fedak PW, et al. Hepatocyte growth factor or vascular endothelial growth factor gene transfer maximizes mesenchymal stem cell-based myocardial salvage after acute myocardial infarction. Circulation. 2009;120(11 Suppl):S247.

    Article  PubMed  CAS  Google Scholar 

  113. Cho J, Zhai P, Maejima Y, Sadoshima J. Myocardial injection with GSK-3beta-overexpressing bone marrow-derived mesenchymal stem cells attenuates cardiac dysfunction after myocardial infarction. Circ Res. 2011;108(4):478.

    Google Scholar 

  114. Chen SL, Fang WW, Ye F, et al. Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction. Am J Cardiol. 2004;94(1):92.

    Article  PubMed  Google Scholar 

  115. Hare JM, Traverse JH, Henry TD, et al. A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction. J Am Coll Cardiol. 2009;54(24):2277.

    Article  PubMed  CAS  Google Scholar 

  116. Galotto M, Berisso G, Delfino L, et al. Stromal damage as consequence of high-dose chemo/radiotherapy in bone marrow transplant recipients. Exp Hematol. 1999;27(9):1460.

    Article  PubMed  CAS  Google Scholar 

  117. Almeida-Porada G, Porada CD, Tran N, Zanjani ED. Cotransplantation of human stromal cell progenitors into preimmune fetal sheep results in early appearance of human donor cells in circulation and boosts cell levels in bone marrow at later time points after transplantation. Blood. 2000;95(11):3620.

    PubMed  CAS  Google Scholar 

  118. Angelopoulou M, Novelli E, Grove JE, et al. Cotransplantation of human mesenchymal stem cells enhances human myelopoiesis and megakaryocytopoiesis in NOD/SCID mice. Exp Hematol. 2003;31(5):413.

    Article  PubMed  CAS  Google Scholar 

  119. Anklesaria P, Kase K, Glowacki J, et al. Engraftment of a clonal bone marrow stromal cell line in vivo stimulates hematopoietic recovery from total body irradiation. Proc Natl Acad Sci USA. 1987;84(21):7681.

    Article  PubMed  CAS  Google Scholar 

  120. Bensidhoum M, Chapel A, Francois S, et al. Homing of in vitro expanded Stro-1- or Stro-1+ human mesenchymal stem cells into the NOD/SCID mouse and their role in supporting human CD34 cell engraftment. Blood. 2004;103(9):3313.

    Article  PubMed  CAS  Google Scholar 

  121. Maitra B, Szekely E, Gjini K, et al. Human mesenchymal stem cells support unrelated donor hematopoietic stem cells and suppress T-cell activation. Bone Marrow Transplant. 2004;33(6):597.

    Article  PubMed  CAS  Google Scholar 

  122. Nolta JA, Hanley MB, Kohn DB. Sustained human hematopoiesis in immunodeficient mice by cotransplantation of marrow stroma expressing human interleukin-3: analysis of gene transduction of long-lived progenitors. Blood. 1994;83(10):3041.

    PubMed  CAS  Google Scholar 

  123. Noort WA, Kruisselbrink AB, in’t Anker PS, et al. Mesenchymal stem cells promote engraftment of human umbilical cord blood-derived CD34(+) cells in NOD/SCID mice. Exp Hematol. 2002;30(8):870.

    Google Scholar 

  124. Gao L, Chen X, Zhang X, et al. Human umbilical cord blood-derived stromal cell, a new resource of feeder layer to expand human umbilical cord blood CD34+ cells in vitro. Blood Cells Mol Dis. 2006;36(2):322.

    Article  PubMed  CAS  Google Scholar 

  125. Zhang C, Chen XH, Zhang X, et al. Human umbilical cord blood-derived stromal cells: a new resource in hematopoietic reconstitution in mouse haploidentical transplantation. Transplant Proc. 2010;42(9):3739.

    Google Scholar 

  126. Walenda T, Bokermann G, Ventura Ferreira MS, et al. Synergistic effects of growth factors and mesenchymal stromal cells for expansion of hematopoietic stem and progenitor cells. Exp Hematol. 2011;39(6):617.

    Article  PubMed  CAS  Google Scholar 

  127. De Toni F, Poglio S, Youcef AB, et al. Human adipose-derived stromal cells efficiently support hematopoiesis in vitro and in vivo: a key step for therapeutic studies. Stem Cells Dev. 2011;20(12):2127.

    Google Scholar 

  128. Devine SM, Bartholomew AM, Mahmud N, et al. Mesenchymal stem cells are capable of homing to the bone marrow of non-human primates following systemic infusion. Exp Hematol. 2001;29(2):244.

    Article  PubMed  CAS  Google Scholar 

  129. Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol. 2008;8(9):726.

    Article  PubMed  CAS  Google Scholar 

  130. Koc ON, Gerson SL, Cooper BW, et al. Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy. J Clin Oncol. 2000;18(2):307.

    PubMed  CAS  Google Scholar 

  131. Lazarus HM, Haynesworth SE, Gerson SL, Rosenthal NS, Caplan AI. Ex vivo expansion and subsequent infusion of human bone marrow-derived stromal progenitor cells (mesenchymal progenitor cells): implications for therapeutic use. Bone Marrow Transplant. 1995;16(4):557.

    PubMed  CAS  Google Scholar 

  132. Ball LM, Bernardo ME, Roelofs H, et al. Cotransplantation of ex vivo expanded mesenchymal stem cells accelerates lymphocyte recovery and may reduce the risk of graft failure in haploidentical hematopoietic stem-cell transplantation. Blood. 2007;110(7):2764.

    Article  PubMed  CAS  Google Scholar 

  133. Fang B, Li N, Song Y, Li J, Zhao RC, Ma Y. Cotransplantation of haploidentical mesenchymal stem cells to enhance engraftment of hematopoietic stem cells and to reduce the risk of graft failure in two children with severe aplastic anemia. Pediatr Transplant. 2009;13(4):499.

    Article  PubMed  Google Scholar 

  134. Fouillard L, Chapel A, Bories D, et al. Infusion of allogeneic-related HLA mismatched mesenchymal stem cells for the treatment of incomplete engraftment following autologous haematopoietic stem cell transplantation. Leukemia. 2007;21(3):568.

    Article  PubMed  CAS  Google Scholar 

  135. Lazarus HM, Koc ON, Devine SM, et al. Cotransplantation of HLA-identical sibling culture-expanded mesenchymal stem cells and hematopoietic stem cells in hematologic malignancy patients. Biol Blood Marrow Transplant. 2005;11(5):389.

    Article  PubMed  Google Scholar 

  136. Le Blanc K, Samuelsson H, Gustafsson B, et al. Transplantation of mesenchymal stem cells to enhance engraftment of hematopoietic stem cells. Leukemia. 2007;21(8):1733.

    Article  PubMed  CAS  Google Scholar 

  137. Macmillan ML, Blazar BR, DeFor TE, Wagner JE. Transplantation of ex vivo culture-expanded parental haploidentical mesenchymal stem cells to promote engraftment in pediatric recipients of unrelated donor umbilical cord blood: results of a phase I–II clinical trial. Bone Marrow Transplant. 2009;43(6):447.

    Article  PubMed  CAS  Google Scholar 

  138. Krampera M, Cosmi L, Angeli R, et al. Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Stem Cells. 2006;24(2):386.

    Article  PubMed  CAS  Google Scholar 

  139. Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 2005;105(4):1815.

    Article  PubMed  CAS  Google Scholar 

  140. Klyushnenkova E, Mosca JD, Zernetkina V, et al. T cell responses to allogeneic human mesenchymal stem cells: immunogenicity, tolerance, and suppression. J Biomed Sci. 2005;12(1):47.

    Article  PubMed  CAS  Google Scholar 

  141. Bocelli-Tyndall C, Bracci L, Spagnoli G, et al. Bone marrow mesenchymal stromal cells (BM-MSCs) from healthy donors and auto-immune disease patients reduce the proliferation of autologous- and allogeneic-stimulated lymphocytes in vitro. Rheumatology (Oxford). 2007;46(3):403.

    Article  CAS  Google Scholar 

  142. Gieseke F, Schutt B, Viebahn S, et al. Human multipotent mesenchymal stromal cells inhibit proliferation of PBMCs independently of IFNgammaR1 signaling and IDO expression. Blood. 2007;110(6):2197.

    Article  PubMed  CAS  Google Scholar 

  143. Chabannes D, Hill M, Merieau E, et al. A role for heme oxygenase-1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells. Blood. 2007;110(10):3691.

    Article  PubMed  CAS  Google Scholar 

  144. Gieseke F, Bohringer J, Bussolari R, Dominici M, Handgretinger R, Muller I. Human multipotent mesenchymal stromal cells use galectin-1 to inhibit immune effector cells. Blood. 2010;116(19):3770.

    Google Scholar 

  145. Meisel R, Zibert A, Laryea M, Gobel U, Daubener W, Dilloo D. Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2, 3-dioxygenase-mediated tryptophan degradation. Blood. 2004;103(12):4619.

    Article  PubMed  CAS  Google Scholar 

  146. Nasef A, Mathieu N, Chapel A, et al. Immunosuppressive effects of mesenchymal stem cells: involvement of HLA-G. Transplantation. 2007;84(2):231.

    Article  PubMed  CAS  Google Scholar 

  147. Nasef A, Mazurier C, Bouchet S, et al. Leukemia inhibitory factor: role in human mesenchymal stem cells mediated immunosuppression. Cell Immunol. 2008;253(1–2):16.

    Article  PubMed  CAS  Google Scholar 

  148. Sato K, Ozaki K, Oh I, et al. Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells. Blood. 2007;109(1):228.

    Article  PubMed  CAS  Google Scholar 

  149. Yang SH, Park MJ, Yoon IH, et al. Soluble mediators from mesenchymal stem cells suppress T cell proliferation by inducing IL-10. Exp Mol Med. 2009;41(5):315.

    Article  PubMed  CAS  Google Scholar 

  150. Augello A, Tasso R, Negrini SM, et al. Bone marrow mesenchymal progenitor cells inhibit lymphocyte proliferation by activation of the programmed death 1 pathway. Eur J Immunol. 2005;35(5):1482.

    Article  PubMed  CAS  Google Scholar 

  151. Liotta F, Angeli R, Cosmi L, et al. Toll-like receptors 3 and 4 are expressed by human bone marrow-derived mesenchymal stem cells and can inhibit their T-cell modulatory activity by impairing Notch signaling. Stem Cells. 2008;26(1):279.

    Article  PubMed  CAS  Google Scholar 

  152. Sheng H, Wang Y, Jin Y, et al. A critical role of IFNgamma in priming MSC-mediated suppression of T cell proliferation through up-regulation of B7–H1. Cell Res. 2008;18(8):846.

    Article  PubMed  CAS  Google Scholar 

  153. Yang HM, Sung JH, Choi YS, et al. Enhancement of the immunosuppressive effect of human adipose tissue-derived mesenchymal stromal cells through HLA-G1 expression. Cytotherapy. 2011 [Epub ahead of print].

  154. Saldanha-Araujo F, Ferreira FI, Palma PV, et al. Mesenchymal stromal cells up-regulate CD39 and increase adenosine production to suppress activated T-lymphocytes. Stem Cell Res. 2011;7(1):66.

    Article  PubMed  CAS  Google Scholar 

  155. Quaedackers ME, Baan CC, Weimar W, Hoogduijn MJ. Cell contact interaction between adipose-derived stromal cells and allo-activated T lymphocytes. Eur J Immunol. 2009;39(12):3436.

    Article  PubMed  CAS  Google Scholar 

  156. Moll G, Jitschin R, von Bahr L, et al. Mesenchymal stromal cells engage complement and complement receptor bearing innate effector cells to modulate immune responses. PLoS One. 2011;6(7):e21703.

    Article  PubMed  CAS  Google Scholar 

  157. Bai L, Lennon DP, Eaton V, et al. Human bone marrow-derived mesenchymal stem cells induce Th2-polarized immune response and promote endogenous repair in animal models of multiple sclerosis. Glia. 2009;57(11):1192.

    Article  PubMed  Google Scholar 

  158. Maccario R, Podesta M, Moretta A, et al. Interaction of human mesenchymal stem cells with cells involved in alloantigen-specific immune response favors the differentiation of CD4+ T-cell subsets expressing a regulatory/suppressive phenotype. Haematologica. 2005;90(4):516.

    PubMed  CAS  Google Scholar 

  159. Ghannam S, Pene J, Torcy-Moquet G, Jorgensen C, Yssel H. Mesenchymal stem cells inhibit human Th17 cell differentiation and function and induce a T regulatory cell phenotype. J Immunol. 2010;185(1):302.

    Article  PubMed  CAS  Google Scholar 

  160. Tabera S, Perez-Simon JA, Diez-Campelo M, et al. The effect of mesenchymal stem cells on the viability, proliferation and differentiation of B-lymphocytes. Haematologica. 2008;93(9):1301.

    Article  PubMed  CAS  Google Scholar 

  161. Asari S, Itakura S, Ferreri K, et al. Mesenchymal stem cells suppress B-cell terminal differentiation. Exp Hematol. 2009;37(5):604.

    Article  PubMed  CAS  Google Scholar 

  162. Zhang W, Ge W, Li C, et al. Effects of mesenchymal stem cells on differentiation, maturation, and function of human monocyte-derived dendritic cells. Stem Cells Dev. 2004;13(3):263.

    Article  PubMed  CAS  Google Scholar 

  163. Jiang XX, Zhang Y, Liu B, et al. Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood. 2005;105(10):4120.

    Article  PubMed  CAS  Google Scholar 

  164. Spaggiari GM, Abdelrazik H, Becchetti F, Moretta L. MSCs inhibit monocyte-derived DC maturation and function by selectively interfering with the generation of immature DCs: central role of MSC-derived prostaglandin E2. Blood. 2009;113(26):6576.

    Article  PubMed  CAS  Google Scholar 

  165. Li YP, Paczesny S, Lauret E, et al. Human mesenchymal stem cells license adult CD34+ hemopoietic progenitor cells to differentiate into regulatory dendritic cells through activation of the Notch pathway. J Immunol. 2008;180(3):1598.

    PubMed  CAS  Google Scholar 

  166. Djouad F, Charbonnier LM, Bouffi C, et al. Mesenchymal stem cells inhibit the differentiation of dendritic cells through an interleukin-6-dependent mechanism. Stem Cells. 2007;25(8):2025.

    Article  PubMed  CAS  Google Scholar 

  167. Selmani Z, Naji A, Zidi I, et al. Human leukocyte antigen-G5 secretion by human mesenchymal stem cells is required to suppress T lymphocyte and natural killer function and to induce CD4+ CD25highFOXP3+ regulatory T cells. Stem Cells. 2008;26(1):212.

    Article  PubMed  CAS  Google Scholar 

  168. Poggi A, Prevosto C, Massaro AM, et al. Interaction between human NK cells and bone marrow stromal cells induces NK cell triggering: role of NKp30 and NKG2D receptors. J Immunol. 2005;175(10):6352.

    PubMed  CAS  Google Scholar 

  169. Nash RA, Antin JH, Karanes C, et al. Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors. Blood. 2000;96(6):2062.

    PubMed  CAS  Google Scholar 

  170. Ratanatharathorn V, Nash RA, Przepiorka D, et al. Phase III study comparing methotrexate and tacrolimus (prograf, FK506) with methotrexate and cyclosporine for graft-versus-host disease prophylaxis after HLA-identical sibling bone marrow transplantation. Blood. 1998;92(7):2303.

    PubMed  CAS  Google Scholar 

  171. Zeiser R, Marks R, Bertz H, Finke J. Immunopathogenesis of acute graft-versus-host disease: implications for novel preventive and therapeutic strategies. Ann Hematol. 2004;83(9):551.

    Article  PubMed  CAS  Google Scholar 

  172. Tian Y, Deng YB, Huang YJ, Wang Y. Bone marrow-derived mesenchymal stem cells decrease acute graft-versus-host disease after allogeneic hematopoietic stem cells transplantation. Immunol Invest. 2008;37(1):29.

    Article  PubMed  CAS  Google Scholar 

  173. Chung NG, Jeong DC, Park SJ, et al. Cotransplantation of marrow stromal cells may prevent lethal graft-versus-host disease in major histocompatibility complex mismatched murine hematopoietic stem cell transplantation. Int J Hematol. 2004;80(4):370.

    Article  PubMed  Google Scholar 

  174. Polchert D, Sobinsky J, Douglas G, et al. IFN-gamma activation of mesenchymal stem cells for treatment and prevention of graft versus host disease. Eur J Immunol. 2008;38(6):1745.

    Article  PubMed  CAS  Google Scholar 

  175. Yanez R, Lamana ML, Garcia-Castro J, Colmenero I, Ramirez M, Bueren JA. Adipose tissue-derived mesenchymal stem cells have in vivo immunosuppressive properties applicable for the control of the graft-versus-host disease. Stem Cells. 2006;24(11):2582.

    Article  PubMed  CAS  Google Scholar 

  176. Aksu AE, Horibe E, Sacks J, et al. Co-infusion of donor bone marrow with host mesenchymal stem cells treats GVHD and promotes vascularized skin allograft survival in rats. Clin Immunol. 2008;127(3):348.

    Article  PubMed  CAS  Google Scholar 

  177. Christensen ME, Turner BE, Sinfield LJ, et al. Mesenchymal stromal cells transiently alter the inflammatory milieu post-transplant to delay graft-versus-host disease. Haematologica. 2010;95(12):2102.

    Article  PubMed  Google Scholar 

  178. Li H, Guo Z, Jiang X, Zhu H, Li X, Mao N. Mesenchymal stem cells alter migratory property of T and dendritic cells to delay the development of murine lethal acute graft-versus-host disease. Stem Cells. 2008;26(10):2531.

    Article  PubMed  CAS  Google Scholar 

  179. Min CK, Kim BG, Park G, Cho B, Oh IH. IL-10-transduced bone marrow mesenchymal stem cells can attenuate the severity of acute graft-versus-host disease after experimental allogeneic stem cell transplantation. Bone Marrow Transplant. 2007;39(10):637.

    Article  PubMed  CAS  Google Scholar 

  180. Tisato V, Naresh K, Girdlestone J, Navarrete C, Dazzi F. Mesenchymal stem cells of cord blood origin are effective at preventing but not treating graft-versus-host disease. Leukemia. 2007;21(9):1992.

    Article  PubMed  CAS  Google Scholar 

  181. Chiesa S, Morbelli S, Morando S, et al. Mesenchymal stem cells impair in vivo T-cell priming by dendritic cells. Proc Natl Acad Sci USA. 2011;108(42):17384.

    Google Scholar 

  182. Hao L, Zhang C, Chen XH, et al. Human umbilical cord blood-derived stromal cells suppress xenogeneic immune cell response in vitro. Croat Med J. 2009;50(4):351.

    Article  PubMed  CAS  Google Scholar 

  183. Hao L, Gao L, Chen XH, et al. Human umbilical cord blood-derived stromal cells prevent graft-versus-host disease in mice following haplo-identical stem cell transplantation. Cytotherapy. 2011;13(1):83.

    Google Scholar 

  184. Sudres M, Norol F, Trenado A, et al. Bone marrow mesenchymal stem cells suppress lymphocyte proliferation in vitro but fail to prevent graft-versus-host disease in mice. J Immunol. 2006;176(12):7761.

    PubMed  CAS  Google Scholar 

  185. Prigozhina TB, Khitrin S, Elkin G, Eizik O, Morecki S, Slavin S. Mesenchymal stromal cells lose their immunosuppressive potential after allotransplantation. Exp Hematol. 2008;36(10):1370.

    Article  PubMed  CAS  Google Scholar 

  186. Le Blanc K, Rasmusson I, Sundberg B, et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. 2004;363(9419):1439.

    Article  PubMed  Google Scholar 

  187. Ringden O, Uzunel M, Rasmusson I, et al. Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease. Transplantation. 2006;81(10):1390.

    Article  PubMed  Google Scholar 

  188. Ning H, Yang F, Jiang M, et al. The correlation between cotransplantation of mesenchymal stem cells and higher recurrence rate in hematologic malignancy patients: outcome of a pilot clinical study. Leukemia. 2008;22(3):593.

    Article  PubMed  CAS  Google Scholar 

  189. Aguayo-Mazzucato C, Bonner-Weir S. Stem cell therapy for type 1 diabetes mellitus. Nat Rev Endocrinol. 2010;6(3):139.

    Google Scholar 

  190. Ianus A, Holz GG, Theise ND, Hussain MA. In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion. J Clin Invest. 2003;111(6):843.

    PubMed  CAS  Google Scholar 

  191. Oh SH, Muzzonigro TM, Bae SH, LaPlante JM, Hatch HM, Petersen BE. Adult bone marrow-derived cells trans-differentiating into insulin-producing cells for the treatment of type I diabetes. Lab Invest. 2004;84(5):607.

    Article  PubMed  CAS  Google Scholar 

  192. Lee RH, Seo MJ, Reger RL, et al. Multipotent stromal cells from human marrow home to and promote repair of pancreatic islets and renal glomeruli in diabetic NOD/scid mice. Proc Natl Acad Sci USA. 2006;103(46):17438.

    Article  PubMed  CAS  Google Scholar 

  193. Urban VS, Kiss J, Kovacs J, et al. Mesenchymal stem cells cooperate with bone marrow cells in therapy of diabetes. Stem Cells. 2008;26(1):244.

    Article  PubMed  CAS  Google Scholar 

  194. Hess D, Li L, Martin M, et al. Bone marrow-derived stem cells initiate pancreatic regeneration. Nat Biotechnol. 2003;21(7):763.

    Article  PubMed  CAS  Google Scholar 

  195. Boumaza I, Srinivasan S, Witt WT, et al. Autologous bone marrow-derived rat mesenchymal stem cells promote PDX-1 and insulin expression in the islets, alter T cell cytokine pattern and preserve regulatory T cells in the periphery and induce sustained normoglycemia. J Autoimmun. 2009;32(1):33.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was partially supported by the National Natural Science Foundation, China (30828007), the Key Projects of Natural Science Foundation of Chongqing (SCTC, 2007BA5011).

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Authors and Affiliations

  1. Department of Internal Medicine, No. 324 Hospital of PLA, Chongqing, 400020, China

    Lei Hao

  2. Institute of Combined Injury, State Key Laboratory of Trauma, Burn and Combined Injury, Third Military Medical University, Chongqing, 400038, China

    Huiqin Sun & Tao Wang

  3. Department of Hematology, Daping Hospital, Chongqing, 400038, China

    Jin Wang

  4. Department of Chemical Defense and Toxicology, Institute of Toxicology, School of Preventive Medicine, Third Military Medical University, Chongqing, 400038, China

    Mingke Wang & Zhongmin Zou

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  1. Lei Hao
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  2. Huiqin Sun
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  4. Tao Wang
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  6. Zhongmin Zou
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Correspondence to Zhongmin Zou.

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Hao, L., Sun, H., Wang, J. et al. Mesenchymal stromal cells for cell therapy: besides supporting hematopoiesis. Int J Hematol 95, 34–46 (2012). https://doi.org/10.1007/s12185-011-0991-8

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