• 1
    European Group for Bone Marrow Transplantation, Allogeneic bone marrow transplantation for leukaemia in Europe. Report from the Working Party on Leukaemia, European Group for Bone Marrow Transplantation. Lancet 1988 1: 13791382.
  • 2
    Lucarelli, G., Polchi, P., Galimberti, M., Izzi, T., Delfini, C., Manna, M., Agostinelli, F. et al., Marrow transplantation for thalassaemia following busulphan and cyclophosphamide. Lancet 1985 1: 13551357.
  • 3
    Boulad, F., Gillio, A., Small, T. N., George, D., Prasad, V., Torok-Castanza, J., Regan, A. D. et al., Stem cell transplantation for the treatment of Fanconi anaemia using a fludarabine-based cytoreductive regimen and T-cell-depleted related HLA-mismatched peripheral blood stem cell grafts. Br. J. Haematol. 2000 111: 11531157.
  • 4
    van Besien, K., Bartholomew, A., Stock, W., Peace, D., Devine, S., Sher, D., Sosman, J. et al., Fludarabine-based conditioning for allogeneic transplantation in adults with sickle cell disease. Bone Marrow Transplant. 2000 26: 445449.
  • 5
    Reisner, Y., Kapoor, N., Kirkpatrick, D., Pollack, M. S., Cunningham-Rundles, S., Dupont, B., Hodes, M. Z. et al., Transplantation for severe combined immunodeficiency with HLA-A,B,D,DR incompatible parental marrow cells fractionated by soybean agglutinin and sheep red blood cells. Blood 1983 61: 341348.
  • 6
    Wulffraat, N., van Royen, A., Bierings, M., Vossen, J. and Kuis, W., Autologous haemopoietic stem-cell transplantation in four patients with refractory juvenile chronic arthritis. Lancet 1999 353: 550553.
  • 7
    Baud, O., Goulet, O., Canioni, D., Le Deist, F., Radford, I., Rieu, D., Dupuis-Girod, S. et al., Treatment of the immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) by allogeneic bone marrow transplantation. N. Engl. J. Med. 2001 344: 17581762.
  • 8
    Friedrich, W., Goldmann, S. F., Vetter, U., Fliedner, T. M., Heymer, B., Peter, H. H., Reisner, Y. and Kleihauer, E., Immunoreconstitution in severe combined immunodeficiency after transplantation of HLA-haploidentical, T-cell-depleted bone marrow. Lancet 1984 1: 761764.
  • 9
    Antoine, C., Muller, S., Cant, A., Cavazzana-Calvo, M., Veys, P., Vossen, J., Fasth, A. et al., Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies: Report of the European experience 1968–99. Lancet 2003 361: 553560.
  • 10
    Spitzer, T. R., Delmonico, F., Tolkoff-Rubin, N., McAfee, S., Sackstein, R., Saidman, S., Colby, C. et al., Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal transplantation for multiple myeloma with end stage renal disease: The induction of allograft tolerance through mixed lymphohematopoietic chimerism. Transplantation 1999 68: 480484.
  • 11
    Kernan, N. A., Bartsch, G., Ash, R. C., Beatty, P. G., Champlin, R., Filipovich, A., Gajewski, J. et al., Analysis of 462 transplantations from unrelated donors facilitated by the National Marrow Donor Program. N. Engl. J. Med. 1993 328: 593602.
  • 12
    Powles, R. L., Morgenstern, G. R., Kay, H. E., McElwain, T. J., Clink, H. M., Dady, P. J., Barrett, A. et al., Mismatched family donors for bone-marrow transplantation as treatment for acute leukaemia. Lancet 1983 1: 612615.
  • 13
    Gale, R. P. and Reisner, Y., Graft rejection and graft-versus-host disease: Mirror images. Lancet 1986 1: 14681470.
  • 14
    Wagner, J. E., Thompson, J. S., Carter, S. L. and Kernan, N. A., Effect of graft-versus-host disease prophylaxis on 3-year disease-free survival in recipients of unrelated donor bone marrow (T-cell Depletion Trial): A multi-centre, randomised Phase II–III trial. Lancet 2005 366: 733741.
  • 15
    Lee, S. J., New approaches for preventing and treating chronic graft-versus-host disease. Blood 2005 105: 42004206.
  • 16
    Bacigalupo, A., Management of acute graft-versus-host disease. Br. J. Haematol. 2007 137: 8798.
  • 17
    Bacigalupo, A. and Palandri, F., Management of acute graft versus host disease (GvHD). Hematol. J. 2004 5: 189196.
  • 18
    Reddy, P. and Ferrara, J. L., Immunobiology of acute graft-versus-host disease. Blood Rev. 2003 17: 187194.
  • 19
    Ferrara, J. L. and Yanik, G., Acute graft versus host disease: Pathophysiology, risk factors, and prevention strategies. Clin. Adv. Hematol. Oncol. 2005 3: 415419, 428.
  • 20
    Andre-Schmutz, I., Le Deist, F., Hacein-Bey-Abina, S., Vitetta, E., Schindler, J., Chedeville, G., Vilmer, E. et al., Immune reconstitution without graft-versus-host disease after haemopoietic stem-cell transplantation: A phase 1/2 study. Lancet 2002 360: 130137.
  • 21
    Michalek, J., Collins, R. H., Hill, B. J., Brenchley, J. M. and Douek, D. C., Identification and monitoring of graft-versus-host specific T-cell clone in stem cell transplantation. Lancet 2003 361: 11831185.
  • 22
    Le Blanc, K., Rasmusson, I., Sundberg, B., Gotherstrom, C., Hassan, M., Uzunel, M. and Ringden, O., Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 2004 363: 14391441.
  • 23
    Le Blanc, K., Frassoni, F., Ball, L., Lanino, E., Sundberg, B., Lonnies, L., Roelofs, H. et al., Mesenchymal stem cells for treatment of severe acute graft-versus-host disease. Blood (ASH Annual Meeting Abstract) 2006 108: 5304a.
  • 24
    Lazarus, H. M., Koc, O. N., Devine, S. M., Curtin, P., Maziarz, R. T., Holland, H. K., Shpall, E. J. 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: 389398.
  • 25
    Tse, W. T., Pendleton, J. D., Beyer, W. M., Egalka, M. C. and Guinan, E. C., Suppression of allogeneic T-cell proliferation by human marrow stromal cells: Implications in transplantation. Transplantation 2003 75: 389397.
  • 26
    Di Nicola, M., Carlo-Stella, C., Magni, M., Milanesi, M., Longoni, P. D., Matteucci, P., Grisanti, S. and Gianni, A. M., Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 2002 99: 38383843.
  • 27
    Bartholomew, A., Sturgeon, C., Siatskas, M., Ferrer, K., McIntosh, K., Patil, S., Hardy, W. et al., Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp. Hematol. 2002 30: 4248.
  • 28
    Krampera, M., Glennie, S., Dyson, J., Scott, D., Laylor, R., Simpson, E. and Dazzi, F., Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood 2003 101: 37223729.
  • 29
    Klyushnenkova, E. N., Shustova, V., Mosca, J.D., Buyaner, D., Hendricks, J.K., Moseley, A.B., and McIntosh, K.R., Human mesenchymal stem cell-mediated suppression of allogeneic T cell responses: A cytokine analysis. FASEB J. 1999 13: A615.
  • 30
    Le Blanc, K., Immunomodulatory effects of fetal and adult mesenchymal stem cells. Cytotherapy 2003 5: 485489.
  • 31
    Potian, J. A., Aviv, H., Ponzio, N. M., Harrison, J. S. and Rameshwar, P., Veto-like activity of mesenchymal stem cells: Functional discrimination between cellular responses to alloantigens and recall antigens. J. Immunol. 2003 171: 34263434.
  • 32
    Chung, N. G., Jeong, D. C., Park, S. J., Choi, B. O., Cho, B., Kim, H. K., Chun, C. S. 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: 370376.
  • 33
    Sudres, M., Norol, F., Trenado, A., Gregoire, S., Charlotte, F., Levacher, B., Lataillade, J. J. 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: 77617767.
  • 34
    Tisato, V., Naresh, K., Girdlestone, J., Navarrete, C. and Dazzi, F., Mesenchymal stem cells of cord blood origin are effective at preventing but not treating graft-versus-host disease. Leukemia 2007 21: 19921999.
  • 35
    Min, C. K., Kim, B. G., Park, G., Cho, B. and Oh, I. H., 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: 637645.
  • 36
    Friedenstein, A., Chailakhjan, R. and Lalykina, K., Heterotopic Transplants of Bone Marrow: Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation 1968 6: 230247.
  • 37
    Baddoo, M., Hill, K., Wilkinson, R., Gaupp, D., Hughes, C., Kopen, G. C. and Phinney, D. G., Characterization of mesenchymal stem cells isolated from murine bone marrow by negative selection. J. Cell. Biochem 2003 89: 12351249.
  • 38
    Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., Moorman, M. A. et al., Multilineage potential of adult human mesenchymal stem cells. Science 1999 284: 143147.
  • 39
    Moadsiri, A., Polchert, D., Genrich, K., Napoles, P., Reina, E., Turian, J., Smith, B. and Bartholomew, A., Mesenchymal stem cells enhance xenochimerism in NK-depleted hosts. Surgery 2006 140: 315321.
  • 40
    Andre-Schmutz, I., Dal Cortivo, L., Fischer, A. and Cavazzana-Calvo, M., Improving immune reconstitution while preventing GvHD in allogeneic stem cell transplantation. Cytotherapy 2005 7: 102108.
  • 41
    Blazar, B. R., Lees, C. J., Martin, P. J., Noelle, R. J., Kwon, B., Murphy, W. and Taylor, P. A., Host T cells resist graft-versus-host disease mediated by donor leukocyte infusions. J. Immunol. 2000 165: 49014909.
  • 42
    Hirayama, M., Azuma, E., Kumamoto, T., Iwamoto, S., Yamada, H., Nashida, Y., Araki, M. et al., Prediction of acute graft-versus-host disease and detection of distinct end-organ targets by enumeration of peripheral blood cytokine spot-forming cells. Transplantation 2005 80: 5865.
  • 43
    Meisel, R., Zibert, A., Laryea, M., Gobel, U., Daubener, W. and Dilloo, D., Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation. Blood 2004 103: 46194621.
  • 44
    Ryan, J. M., Barry, F., Murphy, J. M. and Mahon, B. P., Interferon-gamma does not break, but promotes the immunosuppressive capacity of adult human mesenchymal stem cells. Clin. Exp. Immunol. 2007 149: 353363.
  • 45
    Sato, K., Yamashita, N., Yamashita, N., Baba, M. and Matsuyama, T., Regulatory dendritic cells protect mice from murine acute graft-versus-host disease and leukemia relapse. Immunity 2003 18: 367379.
  • 46
    Le Blanc, K., Tammik, C., Rosendahl, K., Zetterberg, E. and Ringden, O., HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp. Hematol. 2003 31: 890896.
  • 47
    Ringden, O., Uzunel, M., Rasmusson, I., Remberger, M., Sundberg, B., Lonnies, H., Marschall, H. U. et al., Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease. Transplantation 2006 81: 13901397.
  • 48
    Xun, C. Q., Thompson, J. S., Jennings, C. D., Brown, S. A. and Widmer, M. B., Effect of total body irradiation, busulfan-cyclophosphamide, or cyclophosphamide conditioning on inflammatory cytokine release and development of acute and chronic graft-versus-host disease in H-2- incompatible transplanted SCID mice. Blood 1994 83: 23602367.
  • 49
    English, K., Barry, F. P., Field-Corbett, C. P. and Mahon, B. P., IFN-gamma and TNF-alpha differentially regulate immunomodulation by murine mesenchymal stem cells. Immunol. Lett 2007 110: 91100.
  • 50
    Chabannes, D., Hill, M., Merieau, E., Rossignol, J., Brion, R., Soulillou, J. P., Anegon, I. and Cuturi, M. C., A role for heme oxygenase-1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells. Blood 2007 110: 36913694.
  • 51
    Nasef, A., Chapel, A., Mazurier, C., Bouchet, S., Lopez, M., Mathieu, N., Sensebe, L. et al., Identification of IL-10 and TGF-beta transcripts involved in the inhibition of T-lymphocyte proliferation during cell contact with human mesenchymal stem cells. Gene Expr. 2007 13: 217226.
  • 52
    New, J. Y., Li, B., Koh, W. P., Ng, H. K., Tan, S. Y., Yap, E. H., Chan, S. H. and Hu, H. Z., T cell infiltration and chemokine expression: Relevance to the disease localization in murine graft-versus-host disease. Bone Marrow Transplant. 2002 29: 979986.
  • 53
    Wang, L., Li, Y., Chen, X., Chen, J., Gautam, S. C., Xu, Y. and Chopp, M., MCP-1, MIP-1, IL-8 and ischemic cerebral tissue enhance human bone marrow stromal cell migration in interface culture. Hematology 2002 7: 113117.
  • 54
    Croitoru-Lamoury, J., Lamoury, F. M., Zaunders, J. J., Veas, L. A. and Brew, B. J., Human mesenchymal stem cells constitutively express chemokines and chemokine receptors that can be upregulated by cytokines, IFN-beta, and Copaxone. J. Interferon Cytokine Res. 2007 27: 5364.
  • 55
    Zhang, W., Ge, W., Li, C., You, S., Liao, L., Han, Q., Deng, W. and Zhao, R. C., Effects of mesenchymal stem cells on differentiation, maturation, and function of human monocyte-derived dendritic cells. Stem Cells Dev. 2004 13: 263271.
  • 56
    Beyth, S., Borovsky, Z., Mevorach, D., Liebergall, M., Gazit, Z., Aslan, H., Galun, E. and Rachmilewitz, J., Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness. Blood 2005 105: 22142219.
  • 57
    Aggarwal, S. and Pittenger, M. F., Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 2005 105: 18151822.
  • 58
    Gur-Wahnon, D., Borovsky, Z., Beyth, S., Liebergall, M. and Rachmilewitz, J., Contact-dependent induction of regulatory antigen-presenting cells by human mesenchymal stem cells is mediated via STAT3 signaling. Exp. Hematol. 2007 35: 426433.
  • 59
    Szebeni, J., Wang, M. G., Pearson, D. A., Szot, G. L. and Sykes, M., IL-2 inhibits early increases in serum gamma interferon levels associated with graft-versus-host-disease. Transplantation 1994 58: 13851393.
  • 60
    Blazar, B. R., Korngold, R. and Vallera, D. A., Recent advances in graft-versus-host disease (GVHD) prevention. Immunol. Rev. 1997 157: 79109.
  • 61
    Mosmann, T. R., Cherwinski, H., Bond, M. W., Giedlin, M. A. and Coffman, R. L., Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J. Immunol. 1986 136: 23482357.
  • 62
    Phinney, D. G. and Prockop, D. J., Concise review: Mesenchymal stem/multipotent stromal cells: The state of transdifferentiation and modes of tissue repair–Current views. Stem Cells 2007 25: 28962902.
  • 63
    Friedenstein, A., Chailakhjan, R. and Lalykina, K., The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet. 1970 3: 393403.
  • 64
    Witte, P. L., Robinson, M., Henley, A., Low, M. G., Stiers, D. L., Perkins, S., Fleischman, R. A. and Kincade, P. W., Relationships between B-lineage lymphocytes and stromal cells in long- term bone marrow cultures. Eur. J. Immunol. 1987 17: 14731484.
  • 65
    Kopen, G. C., Prockop, D. J. and Phinney, D. G., 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: 1071110716.
  • 66
    Ferrara, J., Guillen, F. J., Sleckman, B., Burakoff, S. J. and Murphy, G. F., Cutaneous acute graft-versus-host disease to minor histocompatibility antigens in a murine model: Histologic analysis and correlation to clinical disease. J. Invest. Dermatol. 1986 86: 371375.
  • 67
    Grass, J. A., Wafa, T., Reames, A., Wages, D., Corash, L., Ferrara, J. L. and Lin, L., Prevention of transfusion-associated graft-versus-host disease by photochemical treatment. Blood 1999 93: 31403147.
  • 68
    Hill, G. R., Crawford, J. M., Cooke, K. R., Brinson, Y. S., Pan, L. and Ferrara, J. L., Total body irradiation and acute graft-versus-host disease: The role of gastrointestinal damage and inflammatory cytokines. Blood 1997 90: 32043213.