Mesenchymal stem cell therapy in the treatment of acute and chronic graft versus host disease

Frontiers in Oncology

Volumn 1, Issue JUL, 2011, Pages

  Kebriaei, Partow ^a   Robinson, Simon ^a  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

Animal models; Clinical trials; Graft versus host disease; Mesenchymal stem cell

Indexed keywords

EID: 84874209081     PISSN: None     EISSN: 2234943X     Source Type: Journal    
DOI: 10.3389/fonc.2011.00016     Document Type: Review

References (78)

1. Aggarwal, S., and Pittenger, M. F. (2005). Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105, 1815-1822.
2. Auletta, J. J., Cooke, K. R., Solchaga, L. A., Deans, R. J., and vant Hof, W. (2010). Regenerative stromal cell therapy in allogeneic hematopoietic stem cell transplantation: current impact and future directions. Biol. Blood Marrow Transplant. 16, 891-906.
3. Beyth, S., Borovsky, Z., Mevorach, D., Liebergall, M., Gazit, Z., Aslan, H., Galun, E., and Rachmilewitz, J. (2005). Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness. Blood 105, 2214-2219.
4. Bieback, K., Hecker, A., Kocaomer, A., Lannert, H., Schallmoser, K., Strunk, D., and Kluter, H. (2009). Human alternatives to fetal bovine serum for the expansion of mesenchymal stromal cells from bone marrow. Stem Cells 27, 2331-2341.
5. Casiraghi, F., Azzollini, N., Cassis, P., Imberti, B., Morigi, M., Cugini, D., Cavinato, R. A., Todeschini, M., Solini, S., Sonzogni, A., Perico, N., Remuzzi, G., and Noris, M. (2008). Pretransplant infusion of mesenchymal stem cells prolongs the survival of a semiallogeneic heart transplant through the generation of regulatory T cells. J. Immunol. 181, 3933-3946.
6. Chapel, A., Bertho, J. M., Bensidhoum, M., Fouillard, L., Young, R. G., Frick, J., Demarquay, C., Cuvelier, F., Mathieu, E., Trompier, F., Dudoignon, N., Germain, C., Mazurier, C., Aigueperse, J., Borneman, J., Gorin, N. C., Gourmelon, P., and Thierry, D. (2003). Mesenchymal stem cells home to injured tissues when co-infused with hematopoietic cells to treat a radiation-induced multi-organ failure syndrome. J. Gene. Med. 5, 1028-1038.
7. Chung, N. G., Jeong, D. C., Park, S. J., Choi, B. O., Cho, B., Kim, H. K., Chun, C. S., Won, J. H., and Han, C. W. (2004). 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. 80, 370-376.
8. Croitoru-Lamoury, J., Lamoury, F. M., Zaunders, J. J., Veas, L. A., and Brew, B. J. (2007). Human mesenchymal stem cells constitutively express chemokines and chemokine receptors that can be upregulated by cytokines, IFN-beta, and Copaxone. J. Interferon Cytokine Res. 27, 53-64.
9. Deans, R. J., and Moseley, A. B. (2000). Mesenchymal stem cells: biology and potential clinical uses. Exp. Hematol. 28, 875-884.
10. Devine, S. M., Cobbs, C., Jennings, M., Bartholomew, A., and Hoffman, R. (2003). Mesenchymal stem cells distribute to a wide range of tissues following systemic infusion into nonhuman primates. Blood 101, 2999-3001.
11. Di Ianni, M., Del Papa, B., De Ioanni, M., Moretti, L., Bonifacio, E., Cecchini, D., Sportoletti, P., Falzetti, F., and Tabilio, A. (2008). Mesenchymal cells recruit and regulate T regulatory cells. Exp. Hematol. 36, 309-318.
12. Di Nicola, M., Carlo-Stella, C., Magni, M., Milanesi, M., Longoni, P. D., Matteucci, P., Grisanti, S., and Gianni, A. M. (2002). Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 99, 3838-3843.
13. Dominici, M., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F., Krause, D., Deans, R., Keating, A., Prockop, D., and Horwitz, E. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8, 315-317.
14. Doucet, C., Ernou, I., Zhang, Y., Llense, J. R., Begot, L., Holy, X., and Lataillade, J. J. (2005). Platelet lysates promote mesenchymal stem cell expansion: a safety substitute for animal serum in cell-based therapy applications. J. Cell. Physiol. 205, 228-236.
15. Fang, B., Song, Y., Zhao, R. C., Han, Q., and Lin, Q. (2007). Using human adipose tissue-derived mesenchymal stem cells as salvage therapy for hepatic graft-versus-host disease resembling acute hepatitis. Transplant. Proc. 39, 1710-1713.
16. Gao, J., Dennis, J. E., Muzic, R. F., Lundberg, M., and Caplan, A. I. (2001). The dynamic in vivo distribution of bone marrow-derived mesenchymal stem cells after infusion. Cells Tissues Organs. 169, 12-20.
17. Gonzalez-Rey, E., Gonzalez, M. A., Varela, N., O'Valle, F., Hernandez-Cortes, P., Rico, L., Buscher, D., and Delgado, M. (2010). Human adipose-derived mesenchymal stem cells reduce inflammatory and T cell responses and induce regulatory T cells in vitro in rheumatoid arthritis. Ann. Rheum. Dis. 69, 241-248.
18. Gur-Wahnon, D., Borovsky, Z., Beyth, S., Liebergall, M., and Rachmilewitz, J. (2007). Contact-dependent induction of regulatory antigen-presenting cells by human mesenchymal stem cells is mediated via STAT3 signaling. Exp. Hematol. 35, 426-433.
19. Hartmann, I., Hollweck, T., Haffner, S., Krebs, M., Meiser, B., Reichart, B., and Eissner, G. (2010). Umbilical cord tissue-derived mesenchymal stem cells grow best under GMP-compliant culture conditions and maintain their phenotypic and functional properties. J. Immunol. Methods 363, 80-89.
20. Horwitz, E. M., Gordon, P. L., Koo, W. K., Marx, J. C., Neel, M. D., McNall, R. Y., Muul, L., and Hofmann, T. (2002). Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: implications for cell therapy of bone. Proc. Natl. Acad. Sci. U.S.A. 99, 8932-8937.
21. Horwitz, E. M., Le Blanc, K., Dominici, M., Mueller, I., Slaper-Cortenbach, I., Marini, F. C., Deans, R. J., Krause, D. S., and Keating, A. (2005). Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy 7, 393-395.
22. Jiang, Y., Jahagirdar, B. N., Reinhardt, R. L., Schwartz, R. E., Keene, C. D., Ortiz-Gonzalez, X. R., Reyes, M., Lenvik, T., Lund, T., Blackstad, M., Du, J., Aldrich, S., Lisberg, A., Low, W. C., Largaespada, D. A., and Verfaillie, C. M. (2002). Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418, 41-49.
23. Joo, S. Y., Cho, K. A., Jung, Y. J., Kim, H. S., Park, S. Y., Choi, Y. B., Hong, K. M., Woo, S. Y., Seoh, J. Y., Cho, S. J., and Ryu, K. H. (2010). Mesenchymal stromal cells inhibit graft-versus-host disease of mice in a dose-dependent manner. Cytotherapy 12, 361-370.
24. Joo, S. Y., Cho, K. A., Jung, Y. J., Kim, H. S., Park, S. Y., Choi, Y. B., Hong, K. M., Woo, S. Y., Seoh, J. Y., and Ryu, K. H. (2011). Bioimaging for the monitoring of the in vivo distribution of infused mesenchymal stem cells in a mouse model of the graft-versus-host reaction. Cell Biol. Int. 35, 417-421.
25. Kavanagh, H., and Mahon, B. P. (2011). Allogeneic mesenchymal stem cells prevent allergic airway inflammation by inducing murine regulatory T cells. Allergy 66, 523-531.
26. Keating, A. (2008). How do mesenchymal stromal cells suppress T cells? Cell Stem Cell 2, 106-108.
27. Kebriaei, P., Isola, L., Bahceci, E., Holland, K., Rowley, S., McGuirk, J., Devetten, M., Jansen, J., Herzig, R., Schuster, M., Monroy, R., and Uberti, J. (2009). Adult human mesenchymal stem cells added to corticosteroid therapy for the treatment of acute graft-versus-host disease. Biol. Blood Marrow Transplant. 15, 804-811.
28. Kocaoemer, A., Kern, S., Kluter, H., and Bieback, K. (2007). Human AB serum and thrombin-activated platelet-rich plasma are suitable alternatives to fetal calf serum for the expansion of mesenchymal stem cells from adipose tissue. Stem Cells 25, 1270-1278.
29. Kurtzberg, J., Prasad, V., Grimley, M. S., Horn, B., Carpenter, P. A., Jacobsen, D., and Prockop, S. (2009). Allogeneic Himan Mesenchymal Stem Cell Therapy (Prochymal) As A Rescue Agent For Severe Treatment Resistant GVHD in Pediatric Patients. Orlando, FL: American Society of Blood and Marrow Transplantation.
30. Kuznetsov, S. A., Mankani, M. H., and Robey, P. G. (2000). Effect of serum on human bone marrow stromal cells: ex vivo expansion and in vivo bone formation. Transplantation 70, 1780-1787.
31. Le Blanc, K., Frassoni, F., Ball, L., Locatelli, F., Roelofs, H., Lewis, I., Lanino, E., Sundberg, B., Bernardo, M. E., Remberger, M., Dini, G., Egeler, R. M., Bacigalupo, A., Fibbe, W., and Ringden, O. (2008). Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 371, 1579-1586.
32. Le Blanc, K., Rasmusson, I., Sundberg, B., Gotherstrom, C., Hassan, M., Uzunel, M., and Ringden, O. (2004). Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 363, 1439-1441
33. Le Blanc, K., Tammik, L., Sundberg, B., Haynesworth, S. E., and Ringden, O. (2003). Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand. J. Immunol. 57, 11-20.
34. Lee, R. H., Pulin, A. A., Seo, M. J., Kota, D. J., Ylostalo, J., Larson, B. L., Semprun-Prieto, L., Delafontaine, P., and Prockop, D. J. (2009). Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell 5, 54-63.
35. Li, J., Zhu, H., Liu, Y., Li, Q., Lu, S., Feng, M., Xu, Y., Huang, L., Ma, C., An, Y., Zhao, R. C., Wang, R., and Qin, C. (2010). Human mesenchymal stem cell transplantation protects against cerebral ischemic injury and upregulates interleukin-10 expression in Macacafascicularis. Brain Res. 1334, 65-72.
36. Lin, H. T., Tarng, Y. W., Chen, Y. C., Kao, C. L., Hsu, C. J., Shyr, Y. M., Ku, H. H., and Chiou, S. H. (2005). Using human plasma supplemented medium to cultivate human bone marrow-derived mesenchymal stem cell and evaluation of its multiple-lineage potential. Transplant. Proc. 37, 4504-4505.
37. Lucchini, G., Introna, M., Dander, E., Rovelli, A., Balduzzi, A., Bonanomi, S., Salvade, A., Capelli, C., Belotti, D., Gaipa, G., Perseghin, P., Vinci, P., Lanino, E., Chiusolo, P., Orofino, M. G., Marktel, S., Golay, J., Rambaldi, A., Biondi, A., D'Amico, G., and Biagi, E. (2010). Platelet-lysate-expanded mesenchymal stromal cells as a salvage therapy for severe resistant graft-versus-host disease in a pediatric population. Biol. Blood Marrow Transplant. 16, 1293-1301.
38. Majore, I., Moretti, P., Stahl, F., Hass, R., and Kasper, C. (2011). Growth and differentiation properties of mesenchymal stromal cell populations derived from whole human umbilical cord. Stem. Cell Rev. 7, 17-31.
39. Martin, B. J., Uberti, J. P., Soiffer, R. J., Klingemann, H., Waller, E. K., Daly, A. S., Herrmann, R. P., and Kebriaei, P. (2010). Prochymal Improves Response Rates In Patients With Steroid-Refractory Acute Graft Versus Host Disease (SR-GVHD) Involving The Liver And Gut: Results Of A Randomized, Placebo-Controlled, Multicenter Phase Iii Trial In GVHD. Orlando, FL: Amercian Society of Bone Marrow Transplantation.
40. McNiece, I., Harrington, J., Turney, J., Kellner, J., and Shpall, E. J. (2004). Ex vivo expansion of cord blood mononuclear cells on mesenchymal stem cells. Cytotherapy 6, 311-317.
41. Mielcarek, M., Storb, R., Georges, G. E., Golubev, L., Nikitine, A., Hwang, B., Nash, R. A., and Torok-Storb, B. (2011). Mesenchymal stromal cells fail to prevent acute graft-versus-host disease and graft rejection after dog leukocyte antigen-haploidentical bone marrow transplantation. Biol. Blood Marrow Transplant. 17, 214-225.
42. Min, C. K., Kim, B. G., Park, G., Cho, B., and Oh, I. H. (2007) 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. 39, 637-645.
43. Muller, I., Kordowich, S., Holzwarth, C., Isensee, G., Lang, P., Neunhoeffer, F., Dominici, M., Greil, J., and Handgretinger, R. (2008). Application of multipotent mesenchymal stromal cells in pediatric patients following allogeneic stem cell transplantation. Blood Cells Mol. Dis. 40, 25-32.
44. Muller, I., Kordowich, S., Holzwarth, C., Spano, C., Isensee, G., Staiber, A., Viebahn, S., Gieseke, F., Langer, H., Gawaz, M. P., Horwitz, E. M., Conte, P., Handgretinger, R., and Dominici, M. (2006). Animal serum-free culture conditions for isolation and expansion of multipotent mesenchymal stromal cells from human BM. Cytotherapy 8, 437-444.
45. Najar, M., Raicevic, G., Boufker, H. I., Fayyad Kazan, H., De Bruyn, C., Meuleman, N., Bron, D., Toungouz, M., and Lagneaux, L. (2010a). Mesenchymal stromal cells use PGE2 to modulate activation and proliferation of lymphocyte subsets: Combined comparison of adipose tissue, Wharton's Jelly and bone marrow sources. Cell Immunol. 264, 171-179.
46. Najar, M., Raicevic, G., Boufker, H. I., Fayyad-Kazan, H., De Bruyn, C., Meuleman, N., Bron, D., Toungouz, M., and Lagneaux, L. (2010b). Adipose-tissue-derived and Wharton's jelly-derived mesenchymal stromal cells suppress lymphocyte responses by secreting leukemia inhibitory factor. Tissue Eng. Part A 16, 3537-3546.
47. New, J. Y., Li, B., Koh, W. P., Ng, H. K., Tan, S. Y., Yap, E. H., Chan, S. H., and Hu, H. Z. (2002). T cell infiltration and chemokine expression: relevance to the disease localization in murine graft-versus-host disease. Bone Marrow Transplant. 29, 979-986.
48. Oreffo, R. O., Virdi, A. S., and Triffitt, J. T. (1997). Modulation of osteogenesis and adipogenesis by human serum in human bone marrow cultures. Eur. J. Cell Biol. 74, 251-261.
49. Osiris Therapeuticsn, Inc. (2009). Osiris therapeutics announces preliminary results for prochymal phase III GvHD trials. Available at: http://investor.osiris.com/
50. Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., Moorman, M. A., Simonetti, D. W., Craig, S., and Marshak, D. R. (1999). Multilineage potential of adult human mesenchymal stem cells. Science 284, 143-147.
51. Pittenger, M. F., and Martin, B. J. (2004). Mesenchymal stem cells and their potential as cardiac therapeutics. Circ. Res. 95, 9-20.
52. Polchert, D., Sobinsky, J., Douglas, G., Kidd, M., Moadsiri, A., Reina, E., Genrich, K., Mehrotra, S., Setty, S., Smith, B., and Bartholomew, A. (2008). IFN-gamma activation of mesenchymal stem cells for treatment and prevention of graft versus host disease. Eur. J. Immunol. 38, 1745-1755.
53. Prevosto, C., Zancolli, M., Canevali, P., Zocchi, M. R., and Poggi, A. (2007). Generation of CD4+ or CD8+ regulatory T cells upon mesenchymal stem cell-lymphocyte interaction. Haematologica 92, 881-888.
54. Prockop, D. J., and Olson, S. D. (2007). Clinical trials with adult stem/progenitor cells for tissue repair: let's not overlook some essential precautions. Blood 109, 3147-3151.
55. Ramasamy, R., Tong, C. K., Seow, H. F., Vidyadaran, S., and Dazzi, F. (2008). The immunosuppressive effects of human bone marrow-derived mesenchymal stem cells target T cell proliferation but not its effector function. Cell Immunol. 251, 131-136.
56. Ringden, O., Uzunel, M., Rasmusson, I., Remberger, M., Sundberg, B., Lonnies, H., Marschall, H. U., Dlugosz, A., Szakos, A., Hassan, Z., Omazic, B., Aschan, J., Barkholt, L., and Le Blanc, K. (2006). Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease. Transplantation 81, 1390-1397.
57. Robinson, S. N., Ng, J., Niu, T., Yang, H., McMannis, J. D., Karandish, S., Kaur, I., Fu, P., Del Angel, M., Messinger, R., Flagge, F., de Lima, M., Decker, W., Xing, D., Champlin, R., and Shpall, E. J. (2006). Superior ex vivo cord blood expansion following co-culture with bone marrow-derived mesenchymal stem cells. Bone Marrow Transplant. 37, 359-366.
58. Schallmoser, K., Bartmann, C., Rohde, E., Reinisch, A., Kashofer, K., Stadelmeyer, E., Drexler, C., Lanzer, G., Linkesch, W., and Strunk, D. (2007). Human platelet lysate can replace fetal bovine serum for clinical-scale expansion of functional mesenchymal stromal cells. Transfusion 47, 1436-1446.
59. Shahdadfar, A., Fronsdal, K., Haug, T., Reinholt, F. P., and Brinchmann, J. E. (2005). 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 239, 1357-1366.
60. Shlomchik, W. D. (2007). Graft-versus-host disease. Nat. Rev. Immunol. 7, 340-352.
61. Spaggiari, G. M., Capobianco, A., Becchetti, S., Mingari, M. C., and Moretta, L. (2006). 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 107, 1484-1490.
62. Stute, N., Holtz, K., Bubenheim, M., Lange, C., Blake, F., and Zander, A. R. (2004). Autologous serum for isolation and expansion of human mesenchymal stem cells for clinical use. Exp. Hematol. 32, 1212-1225.
63. Sudres, M., Norol, F., Trenado, A., Gregoire, S., Charlotte, F., Levacher, B., Lataillade, J. J., Bourin, P., Holy, X., Vernant, J. P., Klatzmann, D., and Cohen, J. L. (2006). Bone marrow mesenchymal stem cells suppress lymphocyte proliferation in vitro but fail to prevent graft-versus-host disease in mice. J. Immunol. 176, 7761-777.
64. Sundin, M., Barrett, A. J., Ringden, O., Uzunel, M., Lonnies, H., Dackland, A. L., Christensson, B., and Blanc, K. L. (2009). HSCT recipients have specific tolerance to MSC but not to the MSC donor. J. Immunother. 32, 755-764.
65. Sundin, M., Ringden, O., Sundberg, B., Nava, S., Gotherstrom, C., and Le Blanc, K. (2007). No alloantibodies against mesenchymal stromal cells, but presence of anti-fetal calf serum antibodies, after transplantation in allogeneic hematopoietic stem cell recipients. Haematologica 929, 1208-1215.
66. Tisato, V., Naresh, K., Girdlestone, J., Navarrete, C., and Dazzi, F. (2007). Mesenchymal stem cells of cord blood origin are effective at preventing but not treating graft-versus-host disease. Leukemia 21, 1992-1999.
67. Toma, C., Pittenger, M. F., Cahill, K. S., Byrne, B. J., and Kessler, P. D. (2002). Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation 105, 93-98.
68. Tong, C. K., Vellasamy, S., Tan, B. C., Abdullah, M., Vidyadaran, S., Seow, H. F., and Ramasamy, R. (2010). Generation of mesenchymal stem cell from human umbilical cord tissue using combination of enzymatic and mechanical disassociation method. Cell Biol. Int. 35, 221-226.
69. Uccelli, A., Moretta, L., and Pistoia, V. (2008). Mesenchymal stem cells in health and disease. Nat. Rev. Immunol. 8, 726-736.
70. von Bonin, M., Stolzel, F., Goedecke, A., Richter, K., Wuschek, N., Holig, K., Platzbecker, U., Illmer, T., Schaich, M., Schetelig, J., Kiani, A., Ordemann, R., Ehninger, G., Schmitz, M., and Bornhauser, M. (2009). Treatment of refractory acute GVHD with third-party MSC expanded in platelet lysate-containing medium. Bone Marrow Transplant. 43, 245-251.
71. Wang, L., Li, Y., Chen, X., Chen, J., Gautam, S. C., Xu, Y., and Chopp, M. (2002). MCP-1, MIP-1, IL-8 and ischemic cerebral tissue enhance human bone marrow stromal cell migration in interface culture. Hematology 7, 113-117.
72. Welniak, L. A., Blazar, B. R., and Murphy, W. J. (2007). Immunobiology of allogeneic hematopoietic stem cell transplantation. Annu. Rev. Immunol. 25, 139-170.
73. Weng, J. Y., Du, X., Geng, S. X., Peng, Y. W., Wang, Z., Lu, Z. S., Wu, S. J., Luo, C. W., Guo, R., Ling, W., Deng, C. X., Liao, P. J., and Xiang, A. P. (2010). Mesenchymal stem cell as salvage treatment for refractory chronic GVHD. Bone Marrow Transplant. 45, 1732-1740.
74. Yamaguchi, M., Hirayama, F., Wakamoto, S., Fujihara, M., Murahashi, H., Sato, N., Ikebuchi, K., Sawada, K., Koike, T., Kuwabara, M., Azuma, H., and Ikeda, H. (2002). Bone marrow stromal cells prepared using AB serum and bFGF for hematopoietic stem cells expansion. Transfusion 42, 921-927.
75. Ye, Z., Wang, Y., Xie, H. Y., and Zheng, S. S. (2008). Immunosuppressive effects of rat mesenchymal stem cells: involvement of CD4+CD25+ regulatory T cells. Hepatobiliary Pancreat. Dis. Int. 7, 608-614.
76. Zhang, Y., Li, C., Jiang, X., Zhang, S., Wu, Y., Liu, B., Tang, P., and Mao, N. (2004a). Human placenta-derived mesenchymal progenitor cells support culture expansion of long-term culture-initiating cells from cord blood CD34+ cells. Exp. Hematol. 32, 657-664.
77. Zhang, W., Ge, W., Li, C., You, S., Liao, L., Han, Q., Deng, W., and Zhao, R. C. (2004b). Effects of mesenchymal stem cells on differentiation, maturation, and function of human monocyte-derived dendritic cells. Stem Cells Dev. 13, 263-271.
78. Zhou, H., Guo, M., Bian, C., Sun, Z., Yang, Z., Zeng, Y., Ai, H., and Zhao, R. C. (2010). Efficacy of bone marrow-derived mesenchymal stem cells in the treatment of sclerodermatous chronic graft-versus-host disease: clinical report. Biol. Blood Marrow Transplant. 16, 403-412.