Mesenchymal stem cells for treatment and prevention of graft-versus-host disease and graft failure after hematopoietic stem cell transplantation and future challenges

Mesenchymal Stem Cell Therapy

Volumn , Issue , 2013, Pages 173-205

  Ringdén, Olle ^a  

^a KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

Author keywords

Graft failure; Graft versus host disease; Hematopoietic stem cell transplantation; Mesenchymal stem cells

Indexed keywords

EID: 84979171566     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-1-62703-200-1_10     Document Type: Chapter

References (206)

1. Ringden O, Deeg HJ (1996) Clinical spectrum of graft-versus-host disease. In: Ferrara JLM, Deeg HJ, Burakoff S (eds) Graft vs host disease. Marcel Dekker, Inc., New York, pp 525-559
2. Storb R, Thomas ED (1985) Graft-versus-host disease in dog and man: the Seattle experience. Immunol Rev 88:215-238
3. van Bekkum DW (1985) Graft-versus-host disease. Marcel Dekker, Inc., New York
4. Dausset J (1958) Iso-leuko-antibodies. Acta Haematol 20:156-166
5. Dupont B, O'Reilly RJ, Pollack MS, Good RA (1980) Histocompatibility testing for clinical bone marrow transplantation and prospects for identification of donors other than HLA genotypically identical siblings. Haematol Blood Transfus 25:121-134
6. Ferrara JL, Levy R, Chao NJ (1999) Pathophysiologic mechanisms of acute graft-vs.-host disease. Biol Blood Marrow Transplant 5:347-356
7. Renkonen R, Hayry P (1987) Cellular infiltrates in the target organs associated with acute graft-versus-host disease. Bone Marrow Transplant 2:333-346
8. Ringden O, Witherspoon RP, Storb R, Ekelund E, Thomas ED (1980) Increased in vitro B-cell IgG secretion during acute graft-versus-host disease and infection. Observations in 50 human marrow transplant recipients. Blood 55:179-186
9. Dicke KA, Tridente G, van Bekkum DW (1969) The selective elimination of immunologically competent cells from bone marrow and lymphocyte cell mixtures. 3. In vitro test for detection of immunocompetent cells in fractionated mouse spleen cell suspensions and primate bone marrow suspensions. Transplantation 8:422-434
10. Korngold R, Sprent J (1987) T cell subsets and graft-versus-host disease. Transplantation 44:335-339
11. Prentice HG, Blacklock HA, Janossy G, Gilmore MJ, Price-Jones L, Tidman N, Trejdosiewicz LK, Skeggs DB, Panjwani D, Ball S et al (1984) Depletion of T lymphocytes in donor marrow prevents significant graft-versus-host disease in matched allogeneic leukaemic marrow transplant recipients. Lancet 1:472-476
12. Thomas E, Storb R, Clift RA, Fefer A, Johnson FL, Neiman PE, Lerner KG, Glucksberg H, Buckner CD (1975) Bone-marrow transplantation (first of two parts). N Engl J Med 292:832-843
13. Thomas ED, Storb R, Clift RA, Fefer A, Johnson L, Neiman PE, Lerner KG, Glucksberg H, Buckner CD (1975) Bone-marrow transplantation (second of two parts). N Engl J Med 292:895-902
14. Meyers JD, Thomas ED (1982) Infection complicating bone marrow transplantation. In: Rubin RH, Young LS (eds) Clinical approach to infection in the immunocompromised host. Plenum Press, New York, pp 507-551
15. Paulin T, Ringden O, Nilsson B (1987) Immunological recovery after bone marrow transplantation: role of age, graft-versus-host disease, prednisolone treatment and infections. Bone Marrow Transplant 1:317-328
16. Ringden O, Klaesson S, Sundberg B, Ljungman P, Lonnqvist B, Persson U (1992) Decreased incidence of graft-versus-host disease and improved survival with methotrexate combined with cyclosporin compared with monotherapy in recipients of bone marrow from donors other than HLA identical siblings. Bone Marrow Transplant 9:19-25
17. Storb R, Deeg HJ, Farewell V, Doney K, Appelbaum F, Beatty P, Bensinger W, Buckner CD, Clift R, Hansen J et al (1986) Marrow transplantation for severe aplastic anemia: methotrexate alone compared with a combination of methotrexate and cyclosporine for prevention of acute graft-versus-host disease. Blood 68:119-125
18. Storb R, Deeg HJ, Whitehead J, Appelbaum F, Beatty P, Bensinger W, Buckner CD, Clift R, Doney K, Farewell V et al (1986) Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia. N Engl J Med 314:729-735
19. Storb R, Kolb HJ, Deeg HJ, Weiden PL, Appelbaum F, Graham TC, Thomas ED (1986) Prevention of graft-versus-host disease by immunosuppressive agents after transplantation of DLA-nonidentical canine marrow. Bone Marrow Transplant 1:167-177
20. Ringden O, Horowitz MM, Sondel P, Gale RP, Biggs JC, Champlin RE, Deeg HJ, Dicke K, Masaoka T, Powles RL et al (1993) Methotrexate, cyclosporine, or both to prevent graft-versus-host disease after HLA-identical sibling bone marrow transplants for early leukemia? Blood 81:1094-1101
21. Groth CG, Gahrton G, Lundgren G, Moller E, Pihlstedt P, Ringden O, Sundelin P (1979) Successful treatment with prednisone and graft-versus-host disease in an allogeneic bone-marrow transplant recipient. Scand J Haematol 22:333-338
22. Mielcarek M, Storer BE, Boeckh M, Carpenter PA, McDonald GB, Deeg HJ, Nash RA, Flowers ME, Doney K, Lee S et al (2009) Initial therapy of acute graft-versus-host disease with low-dose prednisone does not compromise patient outcomes. Blood 113:2888-2894
23. Anasetti C, Hansen JA, Waldmann TA, Appelbaum FR, Davis J, Deeg HJ, Doney K, Martin PJ, Nash R, Storb R et al (1994) Treatment of acute graft-versus-host disease with humanized anti-Tac: an antibody that binds to the interleukin-2 receptor. Blood 84:1320-1327
24. Anasetti C, Martin PJ, Hansen JA, Appelbaum FR, Beatty PG, Doney K, Harkonen S, Jackson A, Reichert T, Stewart P et al (1990) A phase I-II study evaluating the murine anti-IL-2 receptor antibody 2A3 for treatment of acute graft-versus-host disease. Transplantation 50:49-54
25. Deeg HJ, Blazar BR, Bolwell BJ, Long GD, Schuening F, Cunningham J, Rifkin RM, Abhyankar S, Briggs AD, Burt R et al (2001) Treatment of steroid-refractory acute graft-versus-host disease with anti-CD147 monoclonal antibody ABX-CBL. Blood 98:2052-2058
26. Deeg HJ, Loughran TP Jr, Storb R, Kennedy MS, Sullivan KM, Doney K, Appelbaum FR, Thomas ED (1985) Treatment of human acute graft-versus-host disease with antithymocyte globulin and cyclosporine with or without methylprednisolone. Transplantation 40:162-166
27. Gratama JW, Jansen J, Lipovich RA, Tanke HJ, Goldstein G, Zwaan FE (1984) Treatment of acute graft-versus-host disease with monoclonal antibody OKT3. Clinical results and effect on circulating T lymphocytes. Transplantation 38:469-474
28. Remberger M, Aschan J, Barkholt L, Tollemar J, Ringden O (2001) Treatment of severe acute graft-versus-host disease with anti-thymocyte globulin. Clin Transplant 15:147-153
29. Ringden O, Aschan J, Westerberg L (1988) Thalidomide for severe acute graft-versus-host disease. Lancet 2:568
30. Weiden PL, Doney K, Storb R, Thomas ED (1978) Anti-human thymocyte globulin (ATG) for prophylaxis and treatment of graft-versus-host disease in recipients of allogeneic marrow grafts. Transplant Proc 10:213-216
31. Vogelsang GB, Santos GW, Colvin OM, Chen T (1988) Thalidomide for graft-versus-host disease. Lancet 1:827
32. Atkinson K, Horowitz MM, Gale RP, van Bekkum DW, Gluckman E, Good RA, Jacobsen N, Kolb HJ, Rimm AA, Ringden O et al (1990) Risk factors for chronic graft-versus-host disease after HLA-identical sibling bone marrow transplantation. Blood 75:2459-2464
33. Lee SJ, Klein JP, Barrett AJ, Ringden O, Antin JH, Cahn JY, Carabasi MH, Gale RP, Giralt S, Hale GA et al (2002) Severity of chronic graft-versus-host disease: association with treatment-related mortality and relapse. Blood 100:406-414
34. Ringden O, Paulin T, Lonnqvist B, Nilsson B (1985) An analysis of factors predisposing to chronic graft-versus-host disease. Exp Hematol 13:1062-1067
35. Storb R, Prentice RL, Sullivan KM, Shulman HM, Deeg HJ, Doney KC, Buckner CD, Clift RA, Witherspoon RP, Appelbaum FA et al (1983) Predictive factors in chronic graft-versus-host disease in patients with aplastic anemia treated by marrow transplantation from HLA- identical siblings. Ann Intern Med 98:461-466
36. Sullivan KM, Shulman HM, Storb R, Weiden PL, Witherspoon RP, McDonald GB, Schubert MM, Atkinson K, Thomas ED (1981) Chronic graft-versus-host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression. Blood 57:267-276
37. Zecca M, Prete A, Rondelli R, Lanino E, Balduzzi A, Messina C, Fagioli F, Porta F, Favre C, Pession A et al (2002) Chronic graft-versus-host disease in children: incidence, risk factors, and impact on outcome. Blood 100:1192-1200
38. Hildebrandt GC, Fazekas T, Lawitschka A, Bertz H, Greinix H, Halter J, Pavletic SZ, Holler E, Wolff D (2011) Diagnosis and treatment of pulmonary chronic GVHD: report from the consensus conference on clinical practice in chronic GVHD. Bone Marrow Transplant 46:1283-1295
39. Atkinson K, Farewell V, Storb R, Tsoi MS, Sullivan KM, Witherspoon RP, Fefer A, Clift R, Goodell B, Thomas ED (1982) Analysis of late infections after human bone marrow transplantation: role of genotypic nonidentity between marrow donor and recipient and of nonspecific suppressor cells in patients with chronic graft-versus-host disease. Blood 60:714-720
40. Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE, Hackman R, Tsoi MS, Storb R, Thomas ED (1980) Chronic graft-versus-host syndrome in man. A longterm clinicopathologic study of 20 Seattle patients. Am J Med 69:204-217
41. Carlens S, Ringden O, Remberger M, Lonnqvist B, Hagglund H, Klaesson S, Mattsson J, Svahn BM, Winiarski J, Ljungman P et al (1998) Risk factors for chronic graft-versus-host disease after bone marrow transplantation: a retrospective single centre analysis. Bone Marrow Transplant 22:755-761
42. Pavletic SZ, Martin P, Lee SJ, Mitchell S, Jacobsohn D, Cowen EW, Turner ML, Akpek G, Gilman A, McDonald G et al (2006) Measuring therapeutic response in chronic graft-versus-host disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. Response Criteria Working Group report. Biol Blood Marrow Transplant 12:252-266
43. Sullivan KM, Witherspoon RP, Storb R, Weiden P, Flournoy N, Dahlberg S, Deeg HJ, Sanders JE, Doney KC, Appelbaum FR et al (1988) Prednisone and azathioprine compared with prednisone and placebo for treatment of chronic graft-v-host disease: prognostic influence of prolonged thrombocytopenia after allogeneic marrow transplantation. Blood 72:546-554
44. Sullivan KM, Witherspoon RP, Storb R, Deeg HJ, Dahlberg S, Sanders JE, Appelbaum FR, Doney KC, Weiden P, Anasetti C et al (1988) Alternating-day cyclosporine and prednisone for treatment of high-risk chronic graft-v-host disease. Blood 72:555-561
45. Weisdorf DJ (2005) Chronic graft-versus-host disease: where is promise for the future? Leukemia 19:1532-1535
46. Canninga-van Dijk MR, van der Straaten HM, Fijnheer R, Sanders CJ, van den Tweel JG, Verdonck LF (2004) Anti-CD20 monoclonal antibody treatment in 6 patients with therapy-refractory chronic graft-versus-host disease. Blood 104:2603-2606
47. Flowers ME, Apperley JF, van Besien K, Elmaagacli A, Grigg A, Reddy V, Bacigalupo A, Kolb HJ, Bouzas L, Michallet M et al (2008) A multicenter prospective phase 2 randomized study of extracorporeal photopheresis for treatment of chronic graft-versus-host disease. Blood 112:2667-2674
48. Greinix HT, Volc-Platzer B, Kalhs P, Fischer G, Rosenmayr A, Keil F, Honigsmann H, Knobler RM (2000) Extracorporeal photochemotherapy in the treatment of severe steroid-refractory acute graft-versus-host disease: a pilot study. Blood 96:2426-2431
49. Koc S, Leisenring W, Flowers ME, Anasetti C, Deeg HJ, Nash RA, Sanders JE, Witherspoon RP, Storb R, Appelbaum FR et al (2002) Therapy for chronic graft-versus-host disease: a randomized trial comparing cyclosporine plus prednisone versus prednisone alone. Blood 100:48-51
50. Socie G, Devergie A, Cosset JM, Pierga JY, Esperou H, Girinski T, Gluckman E (1990) Low-dose (one gray) total-lymphoid irradiation for extensive, drug-resistant chronic graft-versus-host disease. Transplantation 49:657-658
51. Horowitz MM, Gale RP, Sondel PM, Goldman JM, Kersey J, Kolb HJ, Rimm AA, Ringden O, Rozman C, Speck B et al (1990) Graft-versus-leukemia reactions after bone marrow transplantation. Blood 75:555-562
52. Ringden O, Karlsson H, Olsson R, Omazic B, Uhlin M (2009) The allogeneic graft-versus-cancer effect. Br J Haematol 147:614-633
53. Weiden PL, Flournoy N, Thomas ED, Prentice R, Fefer A, Buckner CD, Storb R (1979) Antileukemic effect of graft-versus-host disease in human recipients of allogeneic-marrow grafts. N Engl J Med 300:1068-1073
54. Fefer A, Sullivan KM, Weiden PL, Buckner CD, Schoch G, Storb R, Thomas ED (1987) Graft versus leukemia effect in man: the relapse rate of acute leukemia is lower after allogeneic than syngeneic marrow transplantation. In: Truitt RL, Gale RP, Bortin MM (eds) Cellular immunotherapy of cancer. A R Liss, New York, pp 401-408
55. Ringden O, Labopin M, Gorin NC, Schmitz N, Schaefer UW, Prentice HG, Bergmann L, Jouet JP, Mandelli F, Blaise D et al (2000) Is there a graft-versus-leukaemia effect in the absence of graft-versus-host disease in patients undergoing bone marrow transplantation for acute leukaemia? Br J Haematol 111:1130-1137
56. Goldman JM, Gale RP, Horowitz MM, Biggs JC, Champlin RE, Gluckman E, Hoffmann RG, Jacobsen SJ, Marmont AM, McGlave PB et al (1988) Bone marrow transplantation for chronic myelogenous leukemia in chronic phase. Increased risk for relapse associated with T-cell depletion. Ann Intern Med 108:806-814
57. Marmont AM, Horowitz MM, Gale RP, Sobocinski K, Ash RC, van Bekkum DW, Champlin RE, Dicke KA, Goldman JM, Good RA et al (1991) T-cell depletion of HLA-identical transplants in leukemia. Blood 78:2120-2130
58. Ringden O, Labopin M, Gluckman E, Reiffers J, Vernant JP, Jouet JP, Harrousseau JL, Fiere D, Bacigalupo A, Frassoni F et al (1996) Graft-versus-leukemia effect in allogeneic marrow transplant recipients with acute leukemia is maintained using cyclosporin A combined with methotrexate as prophylaxis. Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 18:921-929
59. Bostrom L, Ringden O, Nilsson B, Jacobsen N, Zwaan F (1991) Early leukemia, seropositiv-ity for several herpes viruses and chronic graft-versus-host disease are associated with decreased incidence of relapse after allogeneic bone marrow transplantation. Clin Transpl 5:351-358
60. Jacobsen N, Keiding N, Ryder L, Ringden O, Lonnqvist B, Gahrton G, Rajantie J, Siimes M, Volin L, Ruutu T et al (1987) Graft-versus-leukaemia activity associated with cytomegalovirus antibody positive bone marrow donors in acute myeloid leukaemia. Lancet 1:456-457
61. Lonnqvist B, Ringden O, Ljungman P, Wahren B, Gahrton G (1986) Reduced risk of recurrent leukaemia in bone marrow transplant recipients after cytomegalovirus infection. Br J Haematol 63:671-679
62. Nordlander A, Mattsson J, Ringden O, Leblanc K, Gustafsson B, Ljungman P, Svenberg P, Svennilson J, Remberger M (2004) Graft-versus-host disease is associated with a lower relapse incidence after hematopoietic stem cell transplantation in patients with acute lymphoblastic leukemia. Biol Blood Marrow Transplant 10:195-203
63. Ringden O, Sundberg B, Lonnqvist B, Tollemar J, Gahrton G, Nilsson B (1988) Allogeneic bone marrow transplantation for leukemia: factors of importance for long-term survival and relapse. Bone Marrow Transplant 3:281-290
64. Elmaagacli AH, Steckel NK, Koldehoff M, Hegerfeldt Y, Trenschel R, Ditschkowski M, Christoph S, Gromke T, Kordelas L, Ottinger HD et al (2011) Early human cytomegalovirus replication after transplantation is associated with a decreased relapse risk: evidence for a putative virus-versus-leukemia effect in acute myeloid leukemia patients. Blood 118:1402-1412
65. Ringden O, Pavletic SZ, Anasetti C, Barrett AJ, Wang T, Wang D, Antin JH, Di Bartolomeo P, Bolwell BJ, Bredeson C et al (2009) The graft-versus-leukemia effect using matched unrelated donors is not superior to HLA-identical siblings for hematopoietic stem cell transplantation. Blood 113:3110-3118
66. Brooke G, Cook M, Blair C, Han R, Heazlewood C, Jones B, Kambouris M, Kollar K, McTaggart S, Pelekanos R et al (2007) Therapeutic applications of mesenchymal stromal cells. Semin Cell Dev Biol 18:846-858
67. Campagnoli C, Roberts IA, Kumar S, Bennett PR, Bellantuono I, Fisk NM (2001) Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood 98:2396-2402
68. De Ugarte DA, Morizono K, Elbarbary A, Alfonso Z, Zuk PA, Zhu M, Dragoo JL, Ashjian P, Thomas B, Benhaim P et al (2003) Comparison of multi-lineage cells from human adipose tissue and bone marrow. Cells Tissues Organs 174:101-109
69. In't Anker PS, Scherjon SA, de Kleijburg-van Keur C, de Groot-Swings GM, Claas FH, Fibbe WE, Kanhai HH (2004) Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta. Stem Cells 22:1338-1345
70. Yoshimura K, Shigeura T, Matsumoto D, Sato T, Takaki Y, Aiba-Kojima E, Sato K, Inoue K, Nagase T, Koshima I et al (2006) Characterization of freshly isolated and cultured cells derived from the fatty and fluid portions of liposuction aspirates. J Cell Physiol 208:64-76
71. Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP (1968) Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation 6:230-247
72. Haynesworth SE, Baber MA, Caplan AI (1992) Cell surface antigens on human marrow-derived mesenchymal cells are detected by monoclonal antibodies. Bone 13:69-80
73. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143-147
74. Prockop DJ (1997) Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276:71-74
75. Toma C, Pittenger MF, Cahill KS, Byrne BJ, Kessler PD (2002) Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation 105:93-98
76. Haynesworth SE, Baber MA, Caplan AI (1996) Cytokine expression by human marrow-derived mesenchymal progenitor cells in vitro: effects of dexamethasone and IL-1 alpha. J Cell Physiol 166:585-592
77. Majumdar MK, Thiede MA, Mosca JD, Moorman M, Gerson SL (1998) Phenotypic and functional comparison of cultures of marrow-derived mesenchymal stem cells (MSCs) and stromal cells. J Cell Physiol 176:57-66
78. Barry F, Boynton R, Murphy M, Haynesworth S, Zaia J (2001) The SH-3 and SH-4 antibodies recognize distinct epitopes on CD73 from human mesenchymal stem cells. Biochem Biophys Res Commun 289:519-524
79. Liechty KW, MacKenzie TC, Shaaban AF, Radu A, Moseley AM, Deans R, Marshak DR, Flake AW (2000) Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat Med 6:1282-1286
80. Pochampally RR, Neville BT, Schwarz EJ, Li MM, Prockop DJ (2004) Rat adult stem cells (marrow stromal cells) engraft and differentiate in chick embryos without evidence of cell fusion. Proc Natl Acad Sci U S A 101:9282-9285
81. Le Blanc K, Tammik C, Rosendahl K, Zetterberg E, Ringden O (2003) HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol 31:890-896
82. Rasmusson I, Ringden O, Sundberg B, Le Blanc K (2003) Mesenchymal stem cells inhibit the formation of cytotoxic T lymphocytes, but not activated cytotoxic T lymphocytes or natural killer cells. Transplantation 76:1208-1213
83. Tse WT, Pendleton JD, Beyer WM, Egalka MC, Guinan EC (2003) Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation 75:389-397
84. Grinnemo KH, Mansson A, Dellgren G, Klingberg D, Wardell E, Drvota V, Tammik C, Holgersson J, Ringden O, Sylven C et al (2004) Xenoreactivity and engraftment of human mesenchymal stem cells transplanted into infarcted rat myocardium. J Thorac Cardiovasc Surg 127:1293-1300
85. Koc ON, Gerson SL, Cooper BW, Dyhouse SM, Haynesworth SE, Caplan AI, Lazarus HM (2000) 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 18:307-316
86. Horwitz EM, Gordon PL, Koo WK, Marx JC, Neel MD, McNall RY, Muul L, 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
87. Devine SM, Cobbs C, Jennings M, Bartholomew A, Hoffman R (2003) Mesenchymal stem cells distribute to a wide range of tissues following systemic infusion into nonhuman primates. Blood 101:2999-3001
88. Gao J, Dennis JE, Muzic RF, Lundberg M, Caplan AI (2001) The dynamic in vivo distribution of bone marrow-derived mesenchymal stem cells after infusion. Cells Tissues Organs 169:12-20
89. Ringden O, Uzunel M, Rasmusson I, Remberger M, Sundberg B, Lonnies H, Marschall HU, Dlugosz A, Szakos A, Hassan Z et al (2006) Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease. Transplantation 81:1390-1397
90. Ringden O, Uzunel M, Sundberg B, Lonnies L, Nava S, Gustafsson J, Henningsohn L, Le Blanc K (2007) Tissue repair using allogeneic mesenchymal stem cells for hemorrhagic cystitis, pneumomediastinum and perforated colon. Leukemia 21:2271-2276
91. Le Blanc K, Gotherstrom C, Ringden O, Hassan M, McMahon R, Horwitz E, Anneren G, Axelsson O, Nunn J, Ewald U et al (2005) Fetal mesenchymal stem-cell engraftment in bone after in utero transplantation in a patient with severe osteogenesis imperfecta. Transplantation 79:1607-1614
92. Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, McIntosh K, Patil S, Hardy W, Devine S, Ucker D, Deans R et al (2002) Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol 30:42-48
93. Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P, Grisanti S, Gianni AM (2002) Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 99:3838-3843
94. Le Blanc K, Tammik L, Sundberg B, Haynesworth SE, 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
95. Le Blanc K, Rasmusson I, Gotherstrom C, Seidel C, Sundberg B, Sundin M, Rosendahl K, Tammik C, Ringden O (2004) Mesenchymal stem cells inhibit the expression of CD25 (interleukin-2 receptor) and CD38 on phytohaemagglutinin-activated lymphocytes. Scand J Immunol 60:307-315
96. Le Blanc K, Ringden O (2007) Immunomodulation by mesenchymal stem cells and clinical experience. J Intern Med 262:509-525
97. Aggarwal S, Pittenger MF (2005) Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105:1815-1822
98. Jiang XX, Zhang Y, Liu B, Zhang SX, Wu Y, Yu XD, Mao N (2005) Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood 105:4120-4126
99. Nauta AJ, Kruisselbrink AB, Lurvink E, Willemze R, Fibbe WE (2006) Mesenchymal stem cells inhibit generation and function of both CD34 +-derived and monocyte-derived dendritic cells. J Immunol 177:2080-2087
100. Ramasamy R, Fazekasova H, Lam EW, Soeiro I, Lombardi G, Dazzi F (2007) Mesenchymal stem cells inhibit dendritic cell differentiation and function by preventing entry into the cell cycle. Transplantation 83:71-76
101. Corcione A, Benvenuto F, Ferretti E, Giunti D, Cappiello V, Cazzanti F, Risso M, Gualandi F, Mancardi GL, Pistoia V et al (2006) Human mesenchymal stem cells modulate B-cell functions. Blood 107:367-372
102. Glennie S, Soeiro I, Dyson PJ, Lam EW, Dazzi F (2005) Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells. Blood 105:2821-2827
103. Rasmusson I, Le Blanc K, Sundberg B, Ringden O (2007) Mesenchymal stem cells stimulate antibody secretion in human B cells. Scand J Immunol 65:336-343
104. Maccario R, Podesta M, Moretta A, Cometa A, Comoli P, Montagna D, Daudt L, Ibatici A, Piaggio G, Pozzi S et al (2005) 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 90:516-525
105. Selmani Z, Naji A, Zidi I, Favier B, Gaiffe E, Obert L, Borg C, Saas P, Tiberghien P, Rouas- Freiss N et al (2008) 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 26:212-222
106. Kim J, Hematti P (2009) Mesenchymal stem cell-educated macrophages: a novel type of alternatively activated macrophages. Exp Hematol 37:1445-1453
107. Krampera M, Cosmi L, Angeli R, Pasini A, Liotta F, Andreini A, Santarlasci V, Mazzinghi B, Pizzolo G, Vinante F et al (2006) Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Stem Cells 24:386-398
108. Groh ME, Maitra B, Szekely E, Koc ON (2005) Human mesenchymal stem cells require monocyte-mediated activation to suppress alloreactive T cells. Exp Hematol 33:928-934
109. Liu H, Kemeny DM, Heng BC, Ouyang HW, Melendez AJ, Cao T (2006) The immunogenic-ity and immunomodulatory function of osteogenic cells differentiated from mesenchymal stem cells. J Immunol 176:2864-2871
110. Meisel R, Zibert A, Laryea M, Gobel U, Daubener W, Dilloo D (2004) Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation. Blood 103:4619-4621
111. Djouad F, Charbonnier LM, Bouffi C, Louis-Plence P, Bony C, Apparailly F, Cantos C, Jorgensen C, Noel D (2007) Mesenchymal stem cells inhibit the differentiation of dendritic cells through an interleukin-6-dependent mechanism. Stem Cells 25:2025-2032
112. Zhang W, Ge W, Li C, You S, Liao L, Han Q, Deng W, Zhao RC (2004) Effects of mesenchymal stem cells on differentiation, maturation, and function of human monocyte-derived dendritic cells. Stem Cells Dev 13:263-271
113. Beyth S, Borovsky Z, Mevorach D, Liebergall M, Gazit Z, Aslan H, Galun E, Rachmilewitz J (2005) Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness. Blood 105:2214-2219
114. Klyushnenkova E, Mosca JD, Zernetkina V, Majumdar MK, Beggs KJ, Simonetti DW, Deans RJ, McIntosh KR (2005) T cell responses to allogeneic human mesenchymal stem cells: immunogenicity, tolerance, and suppression. J Biomed Sci 12:47-57
115. Sato K, Ozaki K, Oh I, Meguro A, Hatanaka K, Nagai T, Muroi K, Ozawa K (2007) Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells. Blood 109:228-234
116. Chabannes D, Hill M, Merieau E, Rossignol J, Brion R, Soulillou JP, Anegon I, Cuturi MC (2007) A role for heme oxygenase-1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells. Blood 110:3691-3694
117. Rasmusson I, Ringden O, Sundberg B, Le Blanc K (2005) Mesenchymal stem cells inhibit lymphocyte proliferation by mitogens and alloantigens by different mechanisms. Exp Cell Res 305:33-41
118. Cheng L, Qasba P, Vanguri P, Thiede MA (2000) Human mesenchymal stem cells support megakaryocyte and pro-platelet formation from CD34(+) hematopoietic progenitor cells. J Cell Physiol 184:58-69
119. Almeida-Porada G, Flake AW, Glimp HA, Zanjani ED (1999) Cotransplantation of stroma results in enhancement of engraftment and early expression of donor hematopoietic stem cells in utero. Exp Hematol 27:1569-1575
120. In't Anker PS, Noort WA, Kruisselbrink AB, Scherjon SA, Beekhuizen W, Willemze R, Kanhai HH, Fibbe WE (2003) Nonexpanded primary lung and bone marrow-derived mesenchymal cells promote the engraftment of umbilical cord blood-derived CD34(+) cells in NOD/SCID mice. Exp Hematol 31:881-889
121. Lazarus HM, Koc ON, Devine SM, Curtin P, Maziarz RT, Holland HK, Shpall EJ, McCarthy P, Atkinson K, Cooper BW et al (2005) Cotransplantation of HLA-identical sibling culture-expanded mesenchymal stem cells and hematopoietic stem cells in hematologic malignancy patients. Biol Blood Marrow Transplant 11:389-398
122. Sundin M, Orvell C, Rasmusson I, Sundberg B, Ringden O, Le Blanc K (2006) Mesenchymal stem cells are susceptible to human herpesviruses, but viral DNA cannot be detected in the healthy seropositive individual. Bone Marrow Transplant 37:1051-1059
123. Le Blanc K, Rasmusson I, Sundberg B, Gotherstrom C, Hassan M, Uzunel M, Ringden O (2004) Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 363:1439-1441
124. Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, Sundberg B, Bernardo ME, Remberger M et al (2008) Mesenchymal stem cells for treatment of steroidresistant, severe, acute graft-versus-host disease: a phase II study. Lancet 371:1579-1586
125. Fang B, Song Y, Liao L, Zhang Y, Zhao RC (2007) Favorable response to human adipose tissue-derived mesenchymal stem cells in steroid-refractory acute graft-versus-host disease. Transplant Proc 39:3358-3362
126. von Bonin M, Stolzel F, Goedecke A, Richter K, Wuschek N, Holig K, Platzbecker U, Illmer T, Schaich M, Schetelig J et al (2009) Treatment of refractory acute GVHD with third-party MSC expanded in platelet lysate-containing medium. Bone Marrow Transplant 43:245-251
127. Ho SJ, Dyson P, Rawling T, Stevens J, Patton N, To LB, Lewis I (2007) Mesenchymal stem cells for treatment of steroid-resistant graft-versus-host disease. Biol Blood Marrow Transplant 13:46-47
128. Kebriaei P, Isola L, Bahceci E, Holland K, Rowley S, McGuirk J, Devetten M, Jansen J, Herzig R, Schuster M et al (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
129. Lucchini G, Introna M, Dander E, Rovelli A, Balduzzi A, Bonanomi S, Salvade A, Capelli C, Belotti D, Gaipa G et al (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
130. Lim JH, Lee MH, Yi HG, Kim CS, Kim JH, Song SU (2010) Mesenchymal stromal cells for steroid-refractory acute graft-versus-host disease: a report of two cases. Int J Hematol 92:204-207
131. Muller I, Kordowich S, Holzwarth C, Isensee G, Lang P, Neunhoeffer F, Dominici M, Greil J, Handgretinger R (2008) Application of multipotent mesenchymal stromal cells in pediatric patients following allogeneic stem cell transplantation. Blood Cells Mol Dis 40:25-32
132. Muroi K (2009) Treatment of GVHD with mesenchymal stromal cells. Jpn J Transfus Cell Ther 55:182 (in Japanese, Abstract)
133. Wernicke CM, Grunewald TG, Juenger H, Kuci S, Kuci Z, Koehl U, Mueller I, Doering M, Peters C, Lawitschka A et al (2011) Mesenchymal stromal cells for treatment of steroid-refractory GvHD: a review of the literature and two pediatric cases. Int arch Med 4:27
134. Wu KH, Chan CK, Tsai C, Chang YH, Sieber M, Chiu TH, Ho M, Peng CT, Wu HP, Huang JL (2011) Effective treatment of severe steroid-resistant acute graft-versus-host disease with umbilical cord-derived mesenchymal stem cells. Transplantation 91:1412-1416
135. Perez-Simon JA, Lopez-Villar O, Andreu EJ, Rifon J, Muntion S, Campelo MD, Sanchez- Guijo FM, Martinez C, Valcarcel D, Canizo CD (2011) Mesenchymal stem cells expanded in vitro with human serum for the treatment of acute and chronic graft-versus-host disease: results of a phase I/II clinical trial. Haematologica 96:1072-1076
136. Prasad VK, Lucas KG, Kleiner GI, Talano JA, Jacobsohn D, Broadwater G, Monroy R, Kurtzberg J (2011) Efficacy and safety of ex vivo cultured adult human mesenchymal stem cells (Prochymal) in pediatric patients with severe refractory acute graft-versus-host disease in a compassionate use study. Biol Blood Marrow Transplant 17:534-541
137. Martin PJ, Uberti J, Soiffer R, Klingemann HW, Waller EK, Daly AS, Hermann RP, 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. Biol Blood Marrow Transplant 16:S169-S170
138. Arima N, Nakamura F, Fukunaga A, Hirata H, Machida H, Kouno S, Ohgushi H (2010) Single intra-arterial injection of mesenchymal stromal cells for treatment of steroid-refractory acute graft-versus-host disease: a pilot study. Cytotherapy 12:265-268
139. von Bahr L, Sundberg B, Lonnies L, Sander B, Karbach H, Hagglund H, Ljungman P, Gustafsson B, Karlsson H, Le Blanc K et al (2012) Long-term complications, immunologic effects, and role of passage for outcome in mesenchymal stromal cell therapy. Biol Blood Marrow Transplant 18(4):557-564
140. Zhou H, Guo M, Bian C, Sun Z, Yang Z, Zeng Y, Ai H, Zhao RC (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
141. Weng JY, Du X, Geng SX, Peng YW, Wang Z, Lu ZS, Wu SJ, Luo CW, Guo R, Ling W et al (2010) Mesenchymal stem cell as salvage treatment for refractory chronic GVHD. Bone Marrow Transplant 45:1732-1740
142. Tsoi MS, Storb R, Jones E, Weiden PL, Shulman H, Witherspoon R, Atkinson K, Thomas ED (1978) Deposition of IgM and complement at the dermoepidermal junction in acute and chronic cutaneous graft-vs-host disease in man. J Immunol 120:1485-1492
143. Zhang LS, Liu QF, Huang K, Zhang Y, Fan ZP, Huang SL (2009) Mesenchymal stem cells for treatment of steroid-resistant chronic graft-versus-host disease. Zhonghua Nei Ke Za Zhi 48:542-546
144. Ringden O, Keating A (2011) Mesenchymal stromal cells as treatment for chronic GVHD. Bone Marrow Transplant 46:163-164
145. Sun L, Akiyama K, Zhang H, Yamaza T, Hou Y, Zhao S, Xu T, Le A, Shi S (2009) Mesenchymal stem cell transplantation reverses multiorgan dysfunction in systemic lupus erythematosus mice and humans. Stem Cells 27:1421-1432
146. Chung NG, Jeong DC, Park SJ, Choi BO, Cho B, Kim HK, Chun CS, Won JH, Han CW (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
147. Lee ST, Jang JH, Cheong JW, Kim JS, Maemg HY, Hahn JS, Ko YW, Min YH (2002) Treatment of high-risk acute myelogenous leukaemia by myeloablative chemoradiotherapy followed by co-infusion of T cell-depleted haematopoietic stem cells and culture-expanded marrow mesenchymal stem cells from a related donor with one fully mismatched human leucocyte antigen haplotype. Br J Haematol 118:1128-1131
148. Le Blanc K, Samuelsson H, Gustafsson B, Remberger M, Sundberg B, Arvidson J, Ljungman P, Lonnies H, Nava S, Ringden O (2007) Transplantation of mesenchymal stem cells to enhance engraftment of hematopoietic stem cells. Leukemia 21:1733-1738
149. Ning H, Yang F, Jiang M, Hu L, Feng K, Zhang J, Yu Z, Li B, Xu C, Li Y et al (2008) The correlation between cotransplantation of mesenchymal stem cells and higher recurrence rate in hematologic malignancy patients: outcome of a pilot clinical study. Leukemia 22:593-599
150. Baron F, Lechanteur C, Willems E, Bruck F, Baudoux E, Seidel L, Vanbellinghen JF, Hafraoui K, Lejeune M, Gothot A et al (2010) Cotransplantation of mesenchymal stem cells might prevent death from graft-versus-host disease (GVHD) without abrogating graft-versus-tumor effects after HLA-mismatched allogeneic transplantation following nonmyeloablative conditioning. Biol Blood Marrow Transplant 16:838-847
151. Gonzalo-Daganzo R, Regidor C, Martin-Donaire T, Rico MA, Bautista G, Krsnik I, Fores R, Ojeda E, Sanjuan I, Garcia-Marco JA et al (2009) Results of a pilot study on the use of third-party donor mesenchymal stromal cells in cord blood transplantation in adults. Cytotherapy 11:278-288
152. Mattsson J, Ringden O, Storb R (2008) Graft failure after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 14:165-170
153. Macmillan ML, Blazar BR, DeFor TE, Wagner JE (2009) 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 43:447-454
154. Larocca A, Piaggio G, Podesta M, Pitto A, Bruno B, Di Grazia C, Gualandi F, Occhini D, Raiola AM, Dominietto A et al (2006) Boost of CD34 +-selected peripheral blood cells without further conditioning in patients with poor graft function following allogeneic stem cell transplantation. Haematologica 91:935-940
155. Svahn BM, Alvin O, Ringden O, Gardulf A, Remberger M (2006) Costs of allogeneic hematopoietic stem cell transplantation. Transplantation 82:147-153
156. Ball LM, Bernardo ME, Roelofs H, Lankester A, Cometa A, Egeler RM, Locatelli F, Fibbe WE (2007) 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 110:2764-2767
157. Meuleman N, Tondreau T, Ahmad I, Kwan J, Crokaert F, Delforge A, Dorval C, Martiat P, Lewalle P, Lagneaux L et al (2009) Infusion of mesenchymal stromal cells can aid hematopoietic recovery following allogeneic hematopoietic stem cell myeloablative transplant: a pilot study. Stem Cells Dev 18:1247-1252
158. Ringden O (2009) Mesenchymal stromal cells as first-line treatment of graft failure after hematopoietic stem cell transplantation. Stem Cells Dev 18:1243-1246
159. Airey JA, Almeida-Porada G, Colletti EJ, Porada CD, Chamberlain J, Movsesian M, Sutko JL, Zanjani ED (2004) Human mesenchymal stem cells form Purkinje fibers in fetal sheep heart. Circulation 109:1401-1407
160. Pereira RF, O'Hara MD, Laptev AV, Halford KW, Pollard MD, Class R, Simon D, Livezey K, Prockop DJ (1998) Marrow stromal cells as a source of progenitor cells for nonhematopoietic tissues in transgenic mice with a phenotype of osteogenesis imperfecta. Proc Natl Acad Sci U S A 95:1142-1147
161. Groth CG, Ringden O (1984) Transplantation in relation to the treatment of inherited disease. Transplantation 38:319-327
162. Krivit W (1996) Bone marrow transplantation: treatment for globoid cell leukodystrophy, metachromatic leukodystrophy, adrenoleukodystrophy and Hurler syndrome. In: Moser HW, Vinken PJ, Bruijn GW (eds) Handbook of clinical neurology. Elsevier Science, Amsterdam, p 106
163. Hobbs JR (1981) Bone marrow transplantation for inborn errors. Lancet 2:735-739
164. Koc ON, Peters C, Aubourg P, Raghavan S, Dyhouse S, DeGasperi R, Kolodny EH, Yoseph YB, Gerson SL, Lazarus HM et al (1999) Bone marrow-derived mesenchymal stem cells remain host-derived despite successful hematopoietic engraftment after allogeneic transplantation in patients with lysosomal and peroxisomal storage diseases. Exp Hematol 27:1675-1681
165. Horwitz EM, Prockop DJ, Fitzpatrick LA, Koo WW, Gordon PL, Neel M, Sussman M, Orchard P, Marx JC, Pyeritz RE et al (1999) Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med 5:309-313
166. Bruder SP, Fink DJ, Caplan AI (1994) Mesenchymal stem cells in bone development, bone repair, and skeletal regeneration therapy. J Cell Biochem 56:283-294
167. Grande DA, Southerland SS, Manji R, Pate DW, Schwartz SE, Lucas PA (1995) Repair of articular cartilage defects using mesenchymal stem cells. Tissue Eng 1:345-353
168. Wang JS, Shum-Tim D, Galipeau J, Chedrawy E, Eliopoulos N, Chiu RC (2000) Marrow stromal cells for cellular cardiomyoplasty: feasibility and potential clinical advantages. J Thorac Cardiovasc Surg 120:999-1005
169. Young RG, Butler DL, Weber W, Gordon SL, Fink DJ (1997) Mesenchymal stem cell-based repair of rabbit Achilles tendon. Trans Orthop Res Soc 22:249
170. Caplan AI (1991) Mesenchymal stem cells. J Orthop Res 9:641-650
171. Chapel A, Bertho JM, Bensidhoum M, Fouillard L, Young RG, Frick J, Demarquay C, Cuvelier F, Mathieu E, Trompier F et al (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
172. Hassan Z, Remberger M, Svenberg P, Elbander M, Omazic B, Mattsson J, Conrad R, Svahn BM, Ahlgren A, Sairafi D et al (2007) Hemorrhagic cystitis: a retrospective single-center survey. Clin Transplant 21:659-667
173. Ringden O, Ruutu T, Remberger M, Nikoskelainen J, Volin L, Vindelov L, Parkkali T, Lenhoff S, Sallerfors B, Ljungman P et al (1994) A randomized trial comparing busulfan with total body irradiation as conditioning in allogeneic marrow transplant recipients with leukemia: a report from The Nordic Bone Marrow Transplantation Group. Blood 83:2723-2730
174. Ringden O, Leblanc K (2011) Pooled MSCs for treatment of severe hemorrhage. Bone Marrow Transplant 46:1158-1160
175. Rasmusson- F Hamad OA, Lonnios H, Masnusson Pu, Sanchez J, Teramura Y, Nilsson-Ektanlk, P, Nilsson B, Lc Blaue K, (2012) Arc Therapeutic Human mesenchymal stemed cells compatible with Human Blood? Stem cells 30 1565-1574
176. Sato K, Ozaki K, Mori M, Muroi K, Ozawa K (2010) Mesenchymal stromal cells for graft-versus-host disease: basic aspects and clinical outcomes. J Clin Exp Hematop 50:79-89
177. Le Blanc K, Ringden O (2005) Immunobiology of human mesenchymal stem cells and future use in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 11:321-334
178. Fang B, Song Y, Lin Q, Zhang Y, Cao Y, Zhao RC, Ma Y (2007) Human adipose tissue-derived mesenchymal stromal cells as salvage therapy for treatment of severe refractory acute graft-vs.-host disease in two children. Pediatr Transplant 11:814-817
179. Brooke G, Rossetti T, Pelekanos R, Ilic N, Murray P, Hancock S, Antonenas V, Huang G, Gottlieb D, Bradstock K et al (2009) Manufacturing of human placenta-derived mesenchymal stem cells for clinical trials. Br J Haematol 144:571-579
180. Chang CJ, Yen ML, Chen YC, Chien CC, Huang HI, Bai CH, Yen BL (2006) Placenta-derived multipotent cells exhibit immunosuppressive properties that are enhanced in the presence of interferon-gamma. Stem Cells 24:2466-2477
181. Karlsson H, Nava S, Ruhm S, Westgren M, Ringden O (2012) Stromal cells from term fetal membrane are highly suppressive in allogeneic settings in vitro. Clin Exp Immunol 167(3):543-555
182. Donnelly JJ, Xi MS, Rockey JH (1993) A soluble product of human corneal fibroblasts inhibits lymphocyte activation. Enhancement by interferon-gamma. Exp Eye Res 56:157-165
183. Korn JH (1981) Modulation of lymphocyte mitogen responses by cocultured fibroblasts. Cell Immunol 63:374-384
184. Shimabukuro Y, Murakami S, Okada H (1992) Interferon-gamma-dependent immunosuppressive effects of human gingival fibroblasts. Immunology 76:344-347
185. Haniffa MA, Wang XN, Holtick U, Rae M, Isaacs JD, Dickinson AM, Hilkens CM, Collin MP (2007) Adult human fibroblasts are potent immunoregulatory cells and functionally equivalent to mesenchymal stem cells. J Immunol 179:1595-1604
186. Haniffa MA, Collin MP, Buckley CD, Dazzi F (2009) Mesenchymal stem cells: the fibroblasts' new clothes? Haematologica 94:258-263
187. Romani L, Fallarino F, De Luca A, Montagnoli C, D'Angelo C, Zelante T, Vacca C, Bistoni F, Fioretti MC, Grohmann U et al (2008) Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease. Nature 451:211-215
188. Montagnoli C, Fallarino F, Gaziano R, Bozza S, Bellocchio S, Zelante T, Kurup WP, Pitzurra L, Puccetti P, Romani L (2006) Immunity and tolerance to Aspergillus involve functionally distinct regulatory T cells and tryptophan catabolism. J Immunol 176:1712-1723
189. Romani L, Zelante T, De Luca A, Fallarino F, Puccetti P (2008) IL-17 and therapeutic kynure-nines in pathogenic inflammation to fungi. J Immunol 180:5157-5162
190. Ringden O, Meunier F, Tollemar J, Ricci P, Tura S, Kuse E, Viviani MA, Gorin NC, Klastersky J, Fenaux P et al (1991) Efficacy of amphotericin B encapsulated in liposomes (AmBisome) in the treatment of invasive fungal infections in immunocompromised patients. J Antimicrob Chemother 28(Suppl B):73-82
191. Ringden O, Nilsson B (1985) Death by graft-versus-host disease associated with HLA mismatch, high recipient age, low marrow cell dose, and splenectomy. Transplantation 40:39-44
192. Tollemar J, Ringden O, Bostrom L, Nilsson B, Sundberg B (1989) Variables predicting deep fungal infections in bone marrow transplant recipients. Bone Marrow Transplant 4:635-641
193. Karlsson H, Samarasinghe S, Ball LM, Sundberg B, Lankester AC, Dazzi F, Uzunel M, Rao K, Veys P, Le Blanc K et al (2008) Mesenchymal stem cells exert differential effects on alloantigen and virus-specific T-cell responses. Blood 112:532-541
194. Meisel R, Brockers S, Heseler K, Degistirici O, Bulle H, Woite C, Stuhlsatz S, Schwippert W, Jager M, Sorg R et al (2011) Human but not murine multipotent mesenchymal stromal cells exhibit broad-spectrum antimicrobial effector function mediated by indoleamine 2,3-dioxygenase. Leukemia 25:648-654
195. Bernardo ME, Ball LM, Cometa AM, Roelofs H, Zecca M, Avanzini MA, Bertaina A, Vinti L, Lankester A, Maccario R et al (2011) Co-infusion of ex vivo-expanded, parental MSCs prevents life-threatening acute GVHD, but does not reduce the risk of graft failure in pediatric patients undergoing allogeneic umbilical cord blood transplantation. Bone Marrow Transplant 46:200-207
196. Basara N, Blau WI, Romer E, Rudolphi M, Bischoff M, Kirsten D, Sanchez H, Gunzelmann S, Fauser AA (1998) Mycophenolate mofetil for the treatment of acute and chronic GVHD in bone marrow transplant patients. Bone Marrow Transplant 22:61-65
197. Benito AI, Furlong T, Martin PJ, Anasetti C, Appelbaum FR, Doney K, Nash RA, Papayannopoulou T, Storb R, Sullivan KM et al (2001) Sirolimus (rapamycin) for the treatment of steroid-refractory acute graft-versus-host disease. Transplantation 72:1924-1929
198. Bolanos-Meade J, Jacobsohn DA, Margolis J, Ogden A, Wientjes MG, Byrd JC, Lucas DM, Anders V, Phelps M, Grever MR et al (2005) Pentostatin in steroid-refractory acute graft-versus-host disease. J Clin Oncol 23:2661-2668
199. Greinix HT, Worel N, Knobler R (2010) Role of extracorporeal photopheresis (ECP) in treatment of steroid-refractory acute graft-versus-host disease. Biol Blood Marrow Transplant 16:1747-1748, author reply 1749
200. Ho VT, Zahrieh D, Hochberg E, Micale E, Levin J, Reynolds C, Steckel S, Cutler C, Fisher DC, Lee SJ et al (2004) Safety and efficacy of denileukin diftitox in patients with steroid-refractory acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Blood 104:1224-1226
201. Shapira MY, Resnick IB, Bitan M, Ackerstein A, Tsirigotis P, Gesundheit B, Zilberman I, Miron S, Leubovic A, Slavin S et al (2005) Rapid response to alefacept given to patients with steroid resistant or steroid dependent acute graft-versus-host disease: a preliminary report. Bone Marrow Transplant 36:1097-1101
202. Wolf D, von Lilienfeld-Toal M, Wolf AM, Schleuning M, von Bergwelt-Baildon M, Held SA, Brossart P (2012) Novel treatment concepts for graft versus host disease (GvHD). Blood 119(1): 16-25
203. Ringden O, Le Blanc K (2006) Mesenchymal stem cells combined with cyclosporine inhibits cytotoxic T cells. Biol Blood Marrow Transplant 12:693-694
204. Buron F, Perrin H, Malcus C, Hequet O, Thaunat O, Kholopp-Sarda MN, Moulin FT, Morelon E (2009) Human mesenchymal stem cells and immunosuppressive drug interactions in allogeneic responses: an in vitro study using human cells. Transplant Proc 41:3347-3352
205. Parekkadan B, Upadhyay R, Dunham J, Iwamoto Y, Mizoguchi E, Mizoguchi A, Weissleder R, Yarmush ML (2011) Bone marrow stromal cell transplants prevent experimental enterocolitis and require host CD11b + splenocytes. Gastroenterology 140:966-975
206. Ringden O (1986) Cyclosporine in allogeneic bone marrow transplantation. Transplantation 42:445-452