Treatment of inflammatory diseases with mesenchymal stem cells

Inflammation and Allergy - Drug Targets

Volumn 8, Issue 2, 2009, Pages 110-123

  Newman, Robert E ^a   Yoo, Dana ^a   LeRoux, Michelle A ^a   Danilkovitch Miagkova, Alla ^a  

^a OSIRIS THERAPEUTICS INC   (United States)

Author keywords

Cellular target; Clinical trial; Immunogenicity; Immunomodulation; Inflammatory diseases; Mechanism of action; Mesenchymal stem cell; Regeneration

Indexed keywords

APOLIPOPROTEIN B100; BOVINE SERUM ALBUMIN; CYCLOOXYGENASE 2; CYTOKINE; HLA G ANTIGEN; INDOLEAMINE 2,3 DIOXYGENASE; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; PROSTAGLANDIN E2; STEROID; TRANSFORMING GROWTH FACTOR BETA;

ALLOGENEIC STEM CELL TRANSPLANTATION; ALLOIMMUNITY; AUTOLOGOUS STEM CELL TRANSPLANTATION; B LYMPHOCYTE; BACTERIUM; CELL CULTURE; CELL FUNCTION; CELLULAR DISTRIBUTION; CLINICAL TRIAL; CROHN DISEASE; CYTOKINE PRODUCTION; DENDRITIC CELL; EX VIVO STUDY; GRAFT VERSUS HOST REACTION; HEART INFARCTION; HEMATOLOGIC MALIGNANCY; HEMATOPOIETIC STEM CELL; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HLA MATCHING; HOST PATHOGEN INTERACTION; HUMAN; IMMUNE RESPONSE; IMMUNOGENICITY; IMMUNOMODULATION; IMMUNOREGULATION; IMMUNOSUPPRESSIVE TREATMENT; INFLAMMATORY DISEASE; INTERMETHOD COMPARISON; MACROPHAGE; MESENCHYMAL STEM CELL; MESENCHYMAL STEM CELL TRANSPLANTATION; MOLECULAR DYNAMICS; NATURAL KILLER CELL; NEUTROPHIL; NONHUMAN; PARASITE; PROCHYMAL; PROTEIN FUNCTION; REVIEW; T LYMPHOCYTE; TARGET CELL; VIRUS;

ANIMALS; CELL DIFFERENTIATION; CELL MOVEMENT; CLINICAL TRIALS AS TOPIC; CROHN DISEASE; GRAFT VS HOST DISEASE; HISTOCOMPATIBILITY; HUMANS; IMMUNOLOGIC FACTORS; IMMUNOSUPPRESSION; INFLAMMATION; MESENCHYMAL STEM CELL TRANSPLANTATION; MESENCHYMAL STEM CELLS; RECEPTORS, IMMUNOLOGIC; REGENERATION;

EID: 70349501666     PISSN: 18715281     EISSN: None     Source Type: Journal    
DOI: 10.2174/187152809788462635     Document Type: Review

References (103)

1. Friedenstein, A.J.; Chailakhyan, R.K.; Latsinik, N.V.; Panasyuk, A.F.; Keiliss-Borok, I.V. Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation, 1974, 331-340.
2. Bruder, S.P.; Jaiswal, N.; Haynesworth, S.E. Growth kinetics, self-renewal, and the osteogenic potential of purified human mesenchymal stem cells during extensive subcultivation and following cryopreservation. J. Cell Biochem., 1997, 278-294.
3. Haynesworth, S.E.; Goshima, J.; Goldberg, V.M.; Caplan, A.I. Characterization of cells with osteogenic potential from human marrow. Bone, 1992, 81-88.
4. 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.; Marshak, D.R. Multilineage potential of adult human mesenchymal stem cells. Science, 1999, 284, 143-147.
5. Kopen, G.C.; Prockop, D.J.; 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, 10711-10716.
6. Pittenger, M.F.; Martin, B.J. Mesenchymal stem cells and their potential as cardiac therapeutics. Circ. Res., 2004, 95, 9-20.
7. Petersen, B.E.; Bowen, W.C.; Patrene, K.D.; Mars, W.M.; Sullivan, A.K.; Murase, N.; Boggs, S.S.; Greenberger, J.S.; Goff, J.P. Bone marrow as a potential source of hepatic oval cells. Science, 1999, 284, 1168-1170.
8. Honczarenko, M.; Le, Y.; Swierkowski, M.; Ghiran, I.; Glodek, A.M.; Silberstein, L.E. Human bone marrow stromal cells express a distinct set of biologically functional chemokine receptors. Stem Cells, 2006, 24, 1030-1041.
9. Ji, J.F.; He, B.P.; Dheen, S.T.; Tay, S.S. Interactions of chemokines and chemokine receptors mediate the migration of mesenchymal stem cells to the impaired site in the brain after hypoglossal nerve injury. Stem Cells, 2004, 22, 415-427.
10. Ponte, A.L.; Marais, E.; Gallay, N.; Langonne, A.; Delorme, B.; Herault, O.; Charbord, P.; Domenech, J. The in vitro migration capacity of human bone marrow mesenchymal stem cells: comparison of chemokine and growth factor chemotactic activities. Stem Cells, 2007, 25, 1737-1745.
11. Ringe, J.; Strassburg, S.; Neumann, K.; Endres, M.; Notter, M.; Burmester, G.R.; Kaps, C.; Sittinger, M. Towards in situ tissue repair: human mesenchymal stem cells express chemokine receptors CXCR1, CXCR2 and CCR2, and migrate upon stimulation with CXCL8 but not CCL2. J. Cell Biochem., 2007, 101, 135-146.
12. Sordi, V.; Malosio, M.L.; Marchesi, F.; Mercalli, A.; Melzi, R.; Giordano, T.; Belmonte, N.; Ferrari, G.; Leone, B.E.; Bertuzzi, F.; Zerbini, G.; Allavena, P.; Bonifacio, E.; Piemonti, L. Bone marrow mesenchymal stem cells express a restricted set of functionally active chemokine receptors capable of promoting migration to pancreatic islets. Blood, 2005, 106, 419-427.
13. Wang, L.; Li, Y.; Chen, J.; Gautam, S.C.; Zhang, Z.; Lu, M.; Chopp, M. Ischemic cerebral tissue and MCP-1 enhance rat bone marrow stromal cell migration in interface culture. Exp. Hematol., 2002, 30, 831-836.
14. Bartholomew, A.; Sturgeon, C.; Siatskas, M.; Ferrer, K.; McIntosh, K.; Patil, S.; Hardy, W.; Devine, S.; Ucker, D.; Deans, R.; Moseley, A.; Hoffman, R. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp. Hematol., 2002, 30, 42-48.
15. Aggarwal, S.; Pittenger, M.F. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood, 2005, 105, 1815-1822.
16. 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.; Thierry, D. 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., 2003, 5, 1028-1038.
17. Devine, S.M.; 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, 2999-3001.
18. Munoz, J.R.; Stoutenger, B.R.; Robinson, A.P.; Spees, J.L.; Prockop, D.J. Human stem/progenitor cells from bone marrow promote neurogenesis of endogenous neural stem cells in the hippocampus of mice. Proc. Natl. Acad. Sci. USA, 2005, 102, 18171-18176.
19. Prockop, D.J.; Gregory, C.A.; Spees, J.L. One strategy for cell and gene therapy: harnessing the power of adult stem cells to repair tissues. Proc. Natl. Acad. Sci. USA, 2003, 100 (Suppl 1), 11917-11923.
20. Urbanek, K.; Rota, M.; Cascapera, S.; Bearzi, C.; Nascimbene, A.; De Angelis, A.; Hosoda, T.; Chimenti, S.; Baker, M.; Limana, F.; Nurzynska, D.; Torella, D.; Rotatori, F.; Rastaldo, R.; Musso, E.; Quaini, F.; Leri, A.; Kajstura, J.; Anversa, P. Cardiac stem cells possess growth factor-receptor systems that after activation regenerate the infarcted myocardium, improving ventricular function and long-term survival. Circ. Res., 2005, 97, 663-673.
21. O'Donoghue, K.; Chan, J.; de la Fuente, J.; Kennea, N.; Sandison, A.; Anderson, J.R.; Roberts, I.A.; Fisk, N.M. Microchimerism in female bone marrow and bone decades after fetal mesenchymal stem-cell trafficking in pregnancy. Lancet, 2004, 364, 179-182.
22. Tse, W.T.; Pendleton, J.D.; Beyer, W.M.; Egalka, M.C.; Guinan, E.C. Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation, 2003, 75, 389-397.
23. Moretta, A.; Bottino, C.; Vitale, M.; Pende, D.; Cantoni, C.; Mingari, M.C.; Biassoni, R.; Moretta, L.Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu. Rev. Immunol., 2001, 19 197-223.
24. Rasmusson, I.; Ringden, O.; Sundberg, B.; Le Blanc, K. Mesenchymal stem cells inhibit the formation of cytotoxic T lymphocytes, but not activated cytotoxic T lymphocytes or natural killer cells. Transplantation, 2003, 76, 1208-1213.
25. Nasef, A.; Mathieu, N.; Chapel, A.; Frick, J.; Francois, S.; Mazurier, C.; Boutarfa, A.; Bouchet, S.; Gorin, N. C.; Thierry, D.; Fouillard, L. Immunosuppressive effects of mesenchymal stem cells: involvement of HLA-G. Transplantation, 2007, 84, 231-237.
26. Eliopoulos, N.; Stagg, J.; Lejeune, L.; Pommey, S.; Galipeau, J. Allogeneic marrow stromal cells are immune rejected by MHC class I- and class II-mismatched recipient mice. Blood, 2005, 106, 4057-4065.
27. Nauta, A.J.; Westerhuis, G.; Kruisselbrink, A.B.; Lurvink, E.G.; Willemze, R.; Fibbe, W.E. Donor-derived mesenchymal stem cells are immunogenic in an allogeneic host and stimulate donor graft rejection in a nonmyeloablative setting. Blood, 2006, 108, 2114-2120.
28. Poncelet, A.J.; Vercruysse, J.; Saliez, A.; Gianello, P. Although pig allogeneic mesenchymal stem cells are not immunogenic in vitro, intracardiac injection elicits an immune response in vivo. Transplantation, 2007, 83, 783-790.
29. Sakamoto, N.; Tsuji, K.; Muul, L.M.; Lawler, A.M.; Petricoin, E.F.; Candotti, F.; Metcalf, J.A.; Tavel, J.A.; Lane, H.C.; Urba, W.J.; Fox, B.A.; Varki, A.; Lunney, J.K.; Rosenberg, A.S. Bovine apolipoprotein B-100 is a dominant immunogen in therapeutic cell populations cultured in fetal calf serum in mice and humans. Blood, 2007, 110, 501-508.
30. Spees, J.L.; Gregory, C.A.; Singh, H.; Tucker, H.A.; Peister, A.; Lynch, P.J.; Hsu, S.C.; Smith, J.; Prockop, D.J. Internalized antigens must be removed to prepare hypoimmunogenic mesenchymal stem cells for cell and gene therapy. Mol. Ther., 2004, 9, 747-756.
31. Sundin, M.; Ringden, O.; Sundberg, B.; Nava, S.; Gotherstrom, C.; Le Blanc, K.No alloantibodies against mesenchymal stromal cells, but presence of anti-fetal calf serum antibodies, after transplantation in allogeneic hematopoietic stem cell recipients. Haematologica, 2007, 92, 1208-1215.
32. Le Blanc, K.; Rasmusson, I.; Sundberg, B.; Gotherstrom, C.; Hassan, M.; Uzunel, M.; Ringden, O. Treatment of severe acute graftversus-host disease with third party haploidentical mesenchymal stem cells. Lancet, 2004, 363, 1439-1441.
33. Moneret-Vautrin, A.; Wal, J.M.; Guillet-Rossof, F.; Gerard, H.; Boulard, P. Bovine serum albumin immunization: a new risk of allergy during protocols for in vitro fertilization. Allergy, 1991, 46, 228-234.
34. Colten, H.R.; Polakoff, P.L.; Weinstein, S.F.; Strieder, D.J. Immediate hypersensitivity to hog trypsin resulting from industrial exposure. N. Engl. J. Med., 1975, 292, 1050-1053.
35. Orta, M.; Ordoqui, E.; Aranzabal, A.; Fernandez, C.; Bartolome, B.; Sanz, M.L. Anaphylactic reaction after artificial insemination. Ann. Allergy Asthma Immunol., 2003, 90, 446-451.
36. de Benito, V.; de Barrio, M.; de Lopez-Saez, M.P.; Ordoqui, E.; Prieto-Garcia, A.; Sainza, T.; Baeza, M.L. Anaphylactic shock caused by impurities in orgotein preparations. Allergol. Immunopathol. (Madr.), 2001, 29, 272-275.
37. Di Nicola, M.; Carlo-Stella, C.; Magni, M.; Milanesi, M.; Longoni, P.D.; Matteucci, P.; Grisanti, S.; Gianni, A.M. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood, 2002, 99, 3838- 3843.
38. Krampera, M.; Glennie, S.; Dyson, J.; Scott, D.; Laylor, R.; Simpson, E.; 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, 3722-3729.
39. Le Blanc, K. [Mesenchymal stem cells. Basic science and future clinical use]. Lakartidningen, 2002, 99, 1318-1321, 1324.
40. Rasmusson, I.; Ringden, O.; Sundberg, B.; Le Blanc, K. Mesenchymal stem cells inhibit lymphocyte proliferation by mitogens and alloantigens by different mechanisms. Exp. Cell Res., 2005, 305, 33-41.
41. Groh, M.E.; Maitra, B.; Szekely, E.; Koc, O.N. Human mesenchymal stem cells require monocyte-mediated activation to suppress alloreactive T cells. Exp. Hematol., 2005, 33, 928-934.
42. Djouad, F.; Charbonnier, L.M.; Bouffi, C.; Louis-Plence, P.; Bony, C.; Apparailly, F.; Cantos, C.; Jorgensen, C.; Noel, D. Mesenchymal stem cells inhibit the differentiation of dendritic cells through an interleukin-6-dependent mechanism. Stem Cells, 2007, 25, 2025-2032.
43. Ryan, J.M.; Barry, F.; Murphy, J.M.; Mahon, B.P. Interferon-gamma does not break, but promotes the immunosuppressive capacity of adult human mesenchymal stem cells. Clin. Exp. Immunol., 2007, 149, 353-363.
44. Sato, K.; Ozaki, K.; Oh, I.; Meguro, A.; Hatanaka, K.; Nagai, T.; Muroi, K.; Ozawa, K. Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells. Blood, 2007, 109, 228-234.
45. Krampera, M.; Cosmi, L.; Angeli, R.; Pasini, A.; Liotta, F.; Andreini, A.; Santarlasci, V.; Mazzinghi, B.; Pizzolo, G.; Vinante, F.; Romagnani, P.; Maggi, E.; Romagnani, S.; Annunziato, F. Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Stem Cells, 2006, 24, 386-398.
46. 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, 4619-4621.
47. Plumas, J.; Chaperot, L.; Richard, M.J.; Molens, J.P.; Bensa, J.C.; Favrot, M.C. Mesenchymal stem cells induce apoptosis of activated T cells. Leukemia, 2005, 19, 1597-1604.
48. Chabannes, D.; Hill, M.; Merieau, E.; Rossignol, J.; Brion, R.; Soulillou, J.P.; Anegon, I.; Cuturi, M.C. A role for heme oxygenase-1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells. Blood, 2007, 110, 3691-3694.
49. Nasef, A.; Mazurier, C.; Bouchet, S.; Francois, S.; Chapel, A.; Thierry, D.; Gorin, N. C.; Fouillard, L. Leukemia inhibitory factor: Role in human mesenchymal stem cells mediated immunosuppression. Cell Immunol., 2008, 253, 16-22.
50. Nauta, A.J.; Kruisselbrink, A.B.; Lurvink, E.; Willemze, R.; Fibbe, W.E. Mesenchymal stem cells inhibit generation and function of both CD34+-derived and monocyte-derived dendritic cells. J. Immunol., 2006, 177, 2080-2087.
51. Oh, I.; Ozaki, K.; Sato, K.; Meguro, A.; Tatara, R.; Hatanaka, K.; Nagai, T.; Muroi, K.; Ozawa, K. Interferon-gamma and NF-kappaB mediate nitric oxide production by mesenchymal stromal cells. Biochem. Biophys. Res. Commun., 2007, 355, 956-962.
52. Ortiz, L.A.; Dutreil, M.; Fattman, C.; Pandey, A.C.; Torres, G.; Go, K.; Phinney, D.G. Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. Proc. Natl. Acad. Sci. USA, 2007, 104, 11002-11007.
53. Gieseke, F.; Schutt, B.; Viebahn, S.; Koscielniak, E.; Friedrich, W.; Handgretinger, R.; Muller, I. Human multipotent mesenchymal stromal cells inhibit proliferation of PBMCs independently of IFNgammaR1 signaling and IDO expression. Blood, 2007, 110, 2197-2200.
54. Selmani, Z.; Naji, A.; Zidi, I.; Favier, B.; Gaiffe, E.; Obert, L.; Borg, C.; Saas, P.; Tiberghien, P.; Rouas-Freiss, N.; Carosella, E.D.; Deschaseaux, F. 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, 212-222.
55. Djouad, F.; Fritz, V.; Apparailly, F.; Louis-Plence, P.; Bony, C.; Sany, J.; Jorgensen, C.; Noel, D. Reversal of the immunosuppressive properties of mesenchymal stem cells by tumor necrosis factor alpha in collagen-induced arthritis. Arthritis. Rheum., 2005, 52, 1595-1603.
56. Kang, H.S.; Habib, M.; Chan, J.; Abavana, C.; Potian, J.A.; Ponzio, N.M.; Rameshwar, P.A paradoxical role for IFN-gamma in the immune properties of mesenchymal stem cells during viral challenge. Exp. Hematol., 2005, 33, 796-803.
57. Batten, P.; Sarathchandra, P.; Antoniw, J.W.; Tay, S.S.; Lowdell, M.W.; Taylor, P.M.; Yacoub, M. H. Human mesenchymal stem cells induce T cell anergy and downregulate T cell allo-responses via the TH2 pathway: relevance to tissue engineering human heart valves. Tissue Eng., 2006, 12, 2263-2273.
58. Rasmusson, I.; Le Blanc, K.; Sundberg, B.; Ringden, O. Mesenchymal stem cells stimulate antibody secretion in human B cells. Scand. J. Immunol., 2007, 65, 336-343.
59. Sotiropoulou, P.A.; Perez, S.A.; Gritzapis, A.D.; Baxevanis, C.N.; Papamichail, M. Interactions between human mesenchymal stem cells and natural killer cells. Stem Cells, 2006, 24, 74-85.
60. Spaggiari, G.M.; Capobianco, A.; Abdelrazik, H.; Becchetti, F.; Mingari, M.C.; Moretta, L. Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2, 3-dioxygenase and prostaglandin E2. Blood, 2008, 111, 1327-1333.
61. Jiang, X.X.; Zhang, Y.; Liu, B.; Zhang, S.X.; Wu, Y.; Yu, X.D.; Mao, N. Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood, 2005, 105, 4120-4126.
62. Raffaghello, L.; Bianchi, G.; Bertolotto, M.; Montecucco, F.; Busca, A.; Dallegri, F.; Ottonello, L.; Pistoia, V. Human mesenchymal stem cells inhibit neutrophil apoptosis: a model for neutrophil preservation in the bone marrow niche. Stem Cells, 2008, 26, 151-162.
63. Liotta, F.; Angeli, R.; Cosmi, L.; Fili, L.; Manuelli, C.; Frosali, F.; Mazzinghi, B.; Maggi, L.; Pasini, A.; Lisi, V.; Santarlasci, V.; Consoloni, L.; Angelotti, M.L.; Romagnani, P.; Parronchi, P.; Krampera, M.; Maggi, E.; Romagnani, S.; Annunziato, F. 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, 279-289.
64. Augello, A.; Tasso, R.; Negrini, S.M.; Amateis, A.; Indiveri, F.; Cancedda, R.; Pennesi, G. Bone marrow mesenchymal progenitor cells inhibit lymphocyte proliferation by activation of the programmed death 1 pathway. Eur. J. Immunol., 2005, 35, 1482-1490.
65. Prevosto, C.; Zancolli, M.; Canevali, P.; Zocchi, M.R.; Poggi, A. Generation of CD4+ or CD8+ regulatory T cells upon mesenchymal stem cell-lymphocyte interaction. Haematologica, 2007, 92, 881-888.
66. Chan, J.L.; Tang, K.C.; Patel, A.P.; Bonilla, L.M.; Pierobon, N.; Ponzio, N.M.; Rameshwar, P. Antigen-presenting property of mesenchymal stem cells occurs during a narrow window at low levels of interferon-gamma. Blood, 2006, 107, 4817-4824.
67. Majumdar, M.K.; Keane-Moore, M.; Buyaner, D.; Hardy, W.B.; Moorman, M.A.; McIntosh, K.R.; Mosca, J.D. Characterization and functionality of cell surface molecules on human mesenchymal stem cells. J. Biomed. Sci., 2003, 10, 228-241.
68. Morandi, F.; Raffaghello, L.; Bianchi, G.; Meloni, F.; Salis, A.; Millo, E.; Ferrone, S.; Barnaba, V.; Pistoia, V. Immunogenicity of human mesenchymal stem cells in HLA-class I-restricted T-cell responses against viral or tumor-associated antigens. Stem Cells, 2008, 26, 1275-1287.
69. Potian, J.A.; Aviv, H.; Ponzio, N.M.; Harrison, J.S.; Rameshwar, P. Veto-like activity of mesenchymal stem cells: functional discrimination between cellular responses to alloantigens and recall antigens. J. Immunol., 2003, 171, 3426-3434.
70. Weiss, D.J.; Kolls, J.K.; Ortiz, L.A.; Panoskaltsis-Mortari, A.; Prockop, D.J. Stem cells and cell therapies in lung biology and lung diseases. Proc. Am. Thorac. Soc., 2008, 5, 637-667.
71. Rasmusson, I.; Uhlin, M.; Le Blanc, K.; Levitsky, V. Mesenchymal stem cells fail to trigger effector functions of cytotoxic T lymphocytes. J. Leukoc. Biol., 2007, 82, 887-893.
72. Maccario, R.; Podesta, M.; Moretta, A.; Cometa, A.; Comoli, P.; Montagna, D.; Daudt, L.; Ibatici, A.; Piaggio, G.; Pozzi, S.; Frassoni, F.; Locatelli, F. 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, 9, 516-525.
73. Zappia, E.; Casazza, S.; Pedemonte, E.; Benvenuto, F.; Bonanni, I.; Gerdoni, E.; Giunti, D.; Ceravolo, A.; Cazzanti, F.; Frassoni, F.; Mancardi, G.; Uccelli, A. Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergy. Blood, 2005, 106, 1755-1761.
74. Gerdoni, E.; Gallo, B.; Casazza, S.; Musio, S.; Bonanni, I.; Pedemonte, E.; Mantegazza, R.; Frassoni, F.; Mancardi, G.; Pedotti, R.; Uccelli, A. Mesenchymal stem cells effectively modulate pathogenic immune response in experimental autoimmune encephalomyelitis. Ann. Neurol., 2007, 61, 219-227.
75. Kassis, I.; Grigoriadis, N.; Gowda-Kurkalli, B.; Mizrachi-Kol, R.; Ben-Hur, T.; Slavin, S.; Abramsky, O.; Karussis, D. Neuroprotection and immunomodulation with mesenchymal stem cells in chronic experimental autoimmune encephalomyelitis. Arch. Neurol., 2008, 65, 753-761.
76. Glennie, S.; Soeiro, I.; Dyson, P.J.; Lam, E.W.; Dazzi, F. Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells. Blood, 2005, 105, 2821-2827.
77. Benvenuto, F.; Ferrari, S.; Gerdoni, E.; Gualandi, F.; Frassoni, F.; Pistoia, V.; Mancardi, G.; Uccelli, A. Human mesenchymal stem cells promote survival of T cells in a quiescent state. Stem Cells, 2007, 25, 1753-1760.
78. Aarden, L.A.; van Kooten, C. The action of interleukin 6 on lymphoid populations. Ciba. Found. Symp., 1992, 167, 68-74; discussion 74-69.
79. Ward, S.G.; Westwick, J. Chemokines: understanding their role in T-lymphocyte biology. Biochem. J., 1998, 333 457-470.
80. Klyushnenkova, E.; Mosca, J.D.; Zernetkina, V.; Majumdar, M.K.; Beggs, K.J.; Simonetti, D.W.; Deans, R.J.; McIntosh, K.R. T cell responses to allogeneic human mesenchymal stem cells: immunogenicity, tolerance, and suppression. J. Biomed. Sci., 2005, 12, 47-57.
81. Corcione, A.; Benvenuto, F.; Ferretti, E.; Giunti, D.; Cappiello, V.; Cazzanti, F.; Risso, M.; Gualandi, F.; Mancardi, G.L.; Pistoia, V.; Uccelli, A. Human mesenchymal stem cells modulate B-cell functions. Blood, 2006, 107, 367-372.
82. Tabera, S.; Perez-Simon, J.A.; Diez-Campelo, M.; Sanchez-Abarca, L.I.; Blanco, B.; Lopez, A.; Benito, A.; Ocio, E.; Sanchez-Guijo, F.M.; Canizo, C.; San Miguel, J.F. The effect of mesenchymal stem cells on the viability, proliferation and differentiation of B-lymphocytes. Haematologica, 2008, 93, 1301-1309.
83. Comoli, P.; Ginevri, F.; Maccario, R.; Avanzini, M.A.; Marconi, M.; Groff, A.; Cometa, A.; Cioni, M.; Porretti, L.; Barberi, W.; Frassoni, F.; Locatelli, F. Human mesenchymal stem cells inhibit antibody production induced in vitro by allostimulation. Nephrol. Dial. Transplant, 2008, 23, 1196-1202.
84. Traggiai, E.; Volpi, S.; Schena, F.; Gattorno, M.; Ferlito, F.; Moretta, L.; Martini, A. Bone marrow-derived mesenchymal stem cells induce both polyclonal expansion and differentiation of B cells isolated from healthy donors and systemic lupus erythematosus patients. Stem Cells, 2008, 26, 562-569.
85. Beyth, S.; Borovsky, Z.; Mevorach, D.; Liebergall, M.; Gazit, Z.; Aslan, H.; Galun, E.; Rachmilewitz, J. Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness. Blood, 2005, 105, 2214-2219.
86. Zhang, B.; Liu, R.; Shi, D.; Liu, X.; Chen, Y.; Dou, X.; Zhu, X.; Lu, C.; Liang, W.; Liao, L.; Zenke, M.; Zhao, R.C. Mesenchymal stem cells induce mature dendritic cells into a novel Jagged-2-dependent regulatory dendritic cell population. Blood, 2009, 113, 46-57.
87. Spaggiari, G.M.; Capobianco, A.; Becchetti, S.; Mingari, M.C.; 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, 1484-1490.
88. English, K.; Barry, F.P.; Field-Corbett, C.P.; Mahon, B.P. IFN-gamma and TNF-alpha differentially regulate immunomodulation by murine mesenchymal stem cells. Immunol. Lett., 2007, 110, 91-100.
89. Karlsson, H.; Samarasinghe, S.; Ball, L.M.; Sundberg, B.; Lankester, A.C.; Dazzi, F.; Uzunel, M.; Rao, K.; Veys, P.; Le Blanc, K.; Ringden, O.; Amrolia, P.J. Mesenchymal stem cells exert differential effects on alloantigen and virus-specific T-cell responses. Blood, 2008, 112, 532-541.
90. Gazzinelli, R.T.; Ropert, C.; Campos, M.A. Role of the Toll/ interleukin-1 receptor signaling pathway in host resistance and pathogenesis during infection with protozoan parasites. Immunol. Rev., 2004, 201 9-25.
91. Caplan, A.I. Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J. Cell Physiol., 2007, 213, 341-347.
92. Stolzing, A.; Jones, E.; McGonagle, D.; Scutt, A. Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies. Mech. Ageing Dev., 2008, 129, 163-173.
93. Arnulf, B.; Lecourt, S.; Soulier, J.; Ternaux, B.; Lacassagne, M.N.; Crinquette, A.; Dessoly, J.; Sciaini, A.K.; Benbunan, M.; Chomienne, C.; Fermand, J.P.; Marolleau, J.P.; Larghero, J. Phenotypic and functional characterization of bone marrow mesenchymal stem cells derived from patients with multiple myeloma. Leukemia, 2007, 21, 158-163.
94. Corre, J.; Mahtouk, K.; Attal, M.; Gadelorge, M.; Huynh, A.; Fleury-Cappellesso, S.; Danho, C.; Laharrague, P.; Klein, B.; Reme, T.; Bourin, P. Bone marrow mesenchymal stem cells are abnormal in multiple myeloma. Leukemia, 2007, 21, 1079-1088.
95. Giles, F.J.; Keating, A.; Goldstone, A.H.; Avivi, I.; Willman, C.L.; Kantarjian, H.M. Acute myeloid leukemia. Hematol. Am. Soc. Hematol. Educ. Program, 2002, 73-110.
96. Sun, L.Y.; Zhang, H.Y.; Feng, X.B.; Hou, Y.Y.; Lu, L.W.; Fan, L.M. Abnormality of bone marrow-derived mesenchymal stem cells in patients with systemic lupus erythematosus. Lupus, 2007, 16, 121-128.
97. Cipriani, P.; Guiducci, S.; Miniati, I.; Cinelli, M.; Urbani, S.; Marrelli, A.; Dolo, V.; Pavan, A.; Saccardi, R.; Tyndall, A.; Giacomelli, R.; Cerinic, M.M. Impairment of endothelial cell differentiation from bone marrow-derived mesenchymal stem cells: new insight into the pathogenesis of systemic sclerosis. Arthritis Rheum., 2007, 56, 1994-2004.
98. Macmillan, M.L.; Blazar, B.R.; Defor, T.E.; Wagner, J.E. 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, 2008.
99. Lazarus, H.M.; Koc, O.N.; Devine, S.M.; Curtin, P.; Maziarz, R.T.; Holland, H.K.; Shpall, E.J.; McCarthy, P.; Atkinson, K.; Cooper, B.W.; Gerson, S.L.; Laughlin, M.J.; Loberiza, F.R., Jr.; Moseley, A.B.; Bacigalupo, A. Cotransplantation of HLA-identical sibling culture-expanded mesenchymal stem cells and hematopoietic stem cells in hematologic malignancy patients. Biol. Blood Marrow Transplant, 2005, 11, 389-398.
100. 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.; Le Blanc, K. Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease. Transplantation, 2006, 81, 1390-1397.
101. Ball, L.M.; Bernardo, M.E.; Roelofs, H.; Lankester, A.; Cometa, A.; Egeler, R.M.; Locatelli, F.; Fibbe, W.E. 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, 2764-2767.
102. 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.; Ringden, O. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet, 2008, 371, 1579-1586.
103. MacMillan, M.L.; Weisdorf, D.J.; Wagner, J.E.; DeFor, T.E.; Burns, L.J.; Ramsay, N.K.; Davies, S.M.; Blazar, B.R. Response of 443 patients to steroids as primary therapy for acute graft-versus-host disease: comparison of grading systems. Biol. Blood Marrow Transplant, 2002, 8, 387-394.