Update on mesenchymal stem cell-based therapy in lupus and scleroderma

Arthritis Research and Therapy

Volumn 17, Issue 1, 2015, Pages

  Cras, Audrey ^a,b   Farge, Dominique ^a   Carmoi, Thierry ^c   Lataillade, Jean Jacques ^d   Wang, Dan Dan ^e   Sun, Lingyun ^e  

^a SAINT LOUIS HOSPITAL   (France)

^b Fondation Carpentier   (France)

^c University of Paris Descartes   (France)

^d PERCY MILITARY HOSPITAL   (France)

^e THE AFFILIATED DRUM TOWER HOSPITAL OF NANJING UNIVERSITY MEDICAL SCHOOL   (China)

Author keywords

[No Author keywords available]

Indexed keywords

ALLOGENEIC STEM CELL TRANSPLANTATION; BONE MARROW DERIVED MESENCHYMAL STEM CELL; CELL ISOLATION; CLINICAL EFFECTIVENESS; DISEASE SEVERITY; EXPERIMENTAL ANIMAL; HEMATOPOIETIC STEM CELL; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMAN; IN VITRO STUDY; MESENCHYMAL STEM CELL TRANSPLANTATION; MULTICENTER STUDY (TOPIC); NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); REMISSION; REVIEW; SCLERODERMA; SYSTEMIC LUPUS ERYTHEMATOSUS; SYSTEMIC SCLEROSIS; TREATMENT INDICATION; UMBILICAL CORD DERIVED MESENCHYMAL STEM CELL; ANIMAL; IMMUNOLOGY; LUPUS ERYTHEMATOSUS, SYSTEMIC; MESENCHYMAL STROMA CELL; MOUSE; MULTIPOTENT STEM CELL; PROCEDURES; SCLERODERMA, SYSTEMIC; TREATMENT OUTCOME;

ANIMALS; HUMANS; LUPUS ERYTHEMATOSUS, SYSTEMIC; MESENCHYMAL STEM CELL TRANSPLANTATION; MESENCHYMAL STROMAL CELLS; MICE; MULTIPOTENT STEM CELLS; REMISSION INDUCTION; SCLERODERMA, SYSTEMIC; TREATMENT OUTCOME;

EID: 84955339270     PISSN: 14786354     EISSN: 14786362     Source Type: Journal    
DOI: 10.1186/s13075-015-0819-7     Document Type: Review

References (89)

1. Rioux JD, Abbas AK. Paths to understanding the genetic basis of autoimmune disease. Nature. 2005;435:584-9.
2. McGonagle D, McDermott MF. A proposed classification of the immunological diseases. PLoS Med. 2006;3, e297.
3. Boumpas DT, Austin 3rd HA, Vaughn EM, Klippel JH, Steinberg AD, Yarboro CH, et al. Controlled trial of pulse methylprednisolone versus two regimens of pulse cyclophosphamide in severe lupus nephritis. Lancet. 1992;340:741-5.
4. Houssiau FA, Vasconcelos C, D'Cruz D, Sebastiani GD, Garrido Ed Ede R, Danieli MG, et al. Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum. 2002;46:2121-31.
5. Appel GB, Contreras G, Dooley MA, Ginzler EM, Isenberg D, Jayne D, et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol. 2009;20:1103-12.
6. Ginzler EM, Dooley MA, Aranow C, Kim MY, Buyon J, Merrill JT, et al. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med. 2005;353:2219-28.
7. Davies RJ, Sangle SR, Jordan NP, Aslam L, Lewis MJ, Wedgwood R, et al. Rituximab in the treatment of resistant lupus nephritis: therapy failure in rapidly progressive crescentic lupus nephritis. Lupus. 2013;22:574-82.
8. Furie R, Petri M, Zamani O, Cervera R, Wallace DJ, Tegzová D, et al. A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum. 2011;63:3918-30.
9. Doria A, Gatto M, Zen M, Iaccarino L, Punzi L. Optimizing outcome in SLE: treating-to-target and definition of treatment goals. Autoimmun Rev. 2014;13:770-7.
10. Fransen J, Popa-Diaconu D, Hesselstrand R, Carreira P, Valentini G, Beretta L, et al. Clinical prediction of 5-year survival in systemic sclerosis: validation of a simple prognostic model in EUSTAR centres. Ann Rheum Dis. 2011;70:1788-92.
11. van Laar JM, Farge D, Sont JK, Naraghi K, Marjanovic Z, Larghero J, et al. Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial. JAMA. 2014;311:2490-8.
12. Friedenstein AJ, Gorskaja JF, Kulagina NN. Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp Hematol. 1976;4:267-74.
13. Caplan AI. Mesenchymal stem cells. J Orthop Res. 1991;9:641-50.
14. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8:315-7.
15. Le Blanc K, Tammik C, Rosendahl K, Zetterberg E, Ringdén O. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol. 2003;31:890-6.
16. Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem. 2006;98:1076-84.
17. Chamberlain G, Fox J, Ashton B, Middleton J. Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells. 2007;25:2739-49.
18. Chen PM, Yen ML, Liu KJ, Sytwu HK, Yen BL. Immunomodulatory properties of human adult and fetal multipotent mesenchymal stem cells. J Biomed Sci. 2011;18:49.
19. Strioga M, Viswanathan S, Darinskas A, Slaby O, Michalek J. Same or not the same? Comparison of adipose tissue-derived versus bone marrow-derived mesenchymal stem and stromal cells. Stem Cells Dev. 2012;21:2724-52.
20. Dazzi F, Horwood NJ. Potential of mesenchymal stem cell therapy. Curr Opin Oncol. 2007;19:650-5.
21. Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P, et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood. 2002;99:3838-43.
22. Meisel R, Zibert A, Laryea M, Göbel U, Däubener W, Dilloo D. Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation. Blood. 2004;103:4619-21.
23. Glennie S, Soeiro I, Dyson PJ, Lam EW, Dazzi F. Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells. Blood. 2005;105:2821-7.
24. Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 2005;105:1815-22.
25. Zappia E, Casazza S, Pedemonte E, Benvenuto F, Bonanni I, Gerdoni E, et al. Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergy. Blood. 2005;106:1755-61.
26. Maccario R, Podestà M, Moretta A, Cometa A, Comoli P, Montagna D, et al. Interaction of human mesenchymal stem cells with cells involved in alloantigen-specific immune response favors the differentiation of CD4+ T-cell subsets expressing a regulatory/suppressive phenotype. Haematologica. 2005;90:516-25.
27. Comoli P, Ginevri F, Maccario R, Avanzini MA, Marconi M, Groff A, et al. Human mesenchymal stem cells inhibit antibody production induced in vitro by allostimulation. Nephrol Dial Transplant. 2008;23:1196-202.
28. Corcione A, Benvenuto F, Ferretti E, Giunti D, Cappiello V, Cazzanti F, et al. Human mesenchymal stem cells modulate B-cell functions. Blood. 2006;107:367-72.
29. Rosado MM, Bernardo ME, Scarsella M, Conforti A, Giorda E, Biagini S, et al. Inhibition of B-cell proliferation and antibody production by mesenchymal stromal cells is mediated by T cells. Stem Cells Dev. 2015;24:93-103.
30. Rasmusson I, Le Blanc K, Sundberg B, Ringdén O. Mesenchymal stem cells stimulate antibody secretion in human B cells. Scand J Immunol. 2007;65:336-43.
31. Traggiai E, Volpi S, Schena F, Gattorno M, Ferlito F, Moretta L, et al. 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;26:562-9.
32. Jiang XX, Zhang Y, Liu B, Zhang SX, Wu Y, Yu XD, et al. Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood. 2005;105:4120-6.
33. Nauta AJ, Kruisselbrink AB, Lurvink E, Willemze R, Fibbe WE. Mesenchymal stem cells inhibit generation and function of both CD34+-derived and monocyte-derived dendritic cells. J Immunol. 2006;177:2080-7.
34. Ramasamy R, Fazekasova H, Lam EW, Soeiro I, Lombardi G, Dazzi F. Mesenchymal stem cells inhibit dendritic cell differentiation and function by preventing entry into the cell cycle. Transplantation. 2007;83:71-6.
35. Le Blanc K, Ringden O. Immunomodulation by mesenchymal stem cells and clinical experience. J Intern Med. 2007;262:509-25.
36. Deuse T, Stubbendorff M, Tang-Quan K, Phillips N, Kay MA, Eiermann T, et al. Immunogenicity and immunomodulatory properties of umbilical cord lining mesenchymal stem cells. Cell Transplant. 2011;20:655-67.
37. Wegmeyer H, Bröske AM, Leddin M, Kuentzer K, Nisslbeck AK, Hupfeld J, et al. Mesenchymal stromal cell characteristics vary depending on their origin. Stem Cells Dev. 2013;22:2606-18.
38. Bochev I, Elmadjian G, Kyurkchiev D, Tzvetanov L, Altankova I, Tivchev P, et al. Mesenchymal stem cells from human bone marrow or adipose tissue differently modulate mitogen-stimulated B-cell immunoglobulin production in vitro. Cell Biol Int. 2008;32:384-93.
39. Ivanova-Todorova E, Bochev I, Mourdjeva M, Dimitrov R, Bukarev D, Kyurkchiev S, et al. Adipose tissue-derived mesenchymal stem cells are more potent suppressors of dendritic cells differentiation compared to bone marrow-derived mesenchymal stem cells. Immunol Lett. 2009;126:37-42.
40. Karussis DM, Slavin S, Lehmann D, Mizrachi-Koll R, Abramsky O, Ben-Nun A. Prevention of experimental autoimmune encephalomyelitis and induction of tolerance with acute immunosuppression followed by syngeneic bone marrow transplantation. J Immunol. 1992;148:1693-8.
41. Augello A, Tasso R, Negrini SM, Cancedda R, Pennesi G. Cell therapy using allogeneic bone marrow mesenchymal stem cells prevents tissue damage in collagen-induced arthritis. Arthritis Rheum. 2007;56:1175-86.
42. Fiorina P, Jurewicz M, Augello A, Vergani A, Dada S, La Rosa S, et al. Immunomodulatory function of bone marrow-derived mesenchymal stem cells in experimental autoimmune type 1 diabetes. J Immunol. 2009;183:993-1004.
43. Sun L, Akiyama K, Zhang H, Yamaza T, Hou Y, Zhao S, et al. Mesenchymal stem cell transplantation reverses multiorgan dysfunction in systemic lupus erythematosus mice and humans. Stem Cells. 2009;27:1421-32.
44. Zhou K, Zhang H, Jin O, Feng X, Yao G, Hou Y, et al. Transplantation of human bone marrow mesenchymal stem cell ameliorates the autoimmune pathogenesis in MRL/lpr mice. Cell Mol Immunol. 2008;5:417-24.
45. Ma X, Che N, Gu Z, Huang J, Wang D, Liang J, et al. Allogenic mesenchymal stem cell transplantation ameliorates nephritis in lupus mice via inhibition of B-cell activation. Cell Transplant. 2013;22:2279-90.
46. Schena F, Gambini C, Gregorio A, Mosconi M, Reverberi D, Gattorno M, et al. Interferon-gamma-dependent inhibition of B cell activation by bone marrow-derived mesenchymal stem cells in a murine model of systemic lupus erythematosus. Arthritis Rheum. 2010;62:2776-86.
47. Youd M, Blickarz C, Woodworth L, Touzjian T, Edling A, Tedstone J, et al. Allogeneic mesenchymal stem cells do not protect NZBxNZW F1 mice from developing lupus disease. Clin Exp Immunol. 2010;161:176-86.
48. Gu F, Molano I, Ruiz P, Sun L, Gilkeson GS. Differential effect of allogeneic versus syngeneic mesenchymal stem cell transplantation in MRL/lpr and (NZB/NZW)F1 mice. Clin Immunol. 2012;145:142-52.
49. Collins E, Gu F, Qi M, Molano I, Ruiz P, Sun L, et al. Differential efficacy of human mesenchymal stem cells based on source of origin. J Immunol. 2014;193:4381-90.
50. Gu Z, Akiyama K, Ma X, Zhang H, Feng X, Yao G, et al. Transplantation of umbilical cord mesenchymal stem cells alleviates lupus nephritis in MRL/lpr mice. Lupus. 2010;19:1502-14.
51. Chang JW, Hung SP, Wu HH, Wu WM, Yang AH, Tsai HL, et al. Therapeutic effects of umbilical cord blood-derived mesenchymal stem cell transplantation in experimental lupus nephritis. Cell Transplant. 2011;20:245-57.
52. Choi EW, Shin IS, Park SY, Park JH, Kim JS, Yoon EJ, et al. Reversal of serologic, immunologic, and histologic dysfunction in mice with systemic lupus erythematosus by long-term serial adipose tissue-derived mesenchymal stem cell transplantation. Arthritis Rheum. 2012;64:243-53.
53. Derrett-Smith EC, Denton CP, Sonnylal S. Animal models of scleroderma: lessons from transgenic and knockout mice. Curr Opin Rheumatol. 2009;21:630-5.
54. Servettaz A, Goulvestre C, Kavian N, Nicco C, Guilpain P, Chéreau C, et al. Selective oxidation of DNA topoisomerase 1 induces systemic sclerosis in the mouse. J Immunol. 2009;182:5855-64.
55. Kumamoto M, Nishiwaki T, Matsuo N, Kimura H, Matsushima K. Minimally cultured bone marrow mesenchymal stem cells ameliorate fibrotic lung injury. Eur Respir J. 2009;34:740-8.
56. Moodley Y, Atienza D, Manuelpillai U, Samuel CS, Tchongue J, Ilancheran S, et al. Human umbilical cord mesenchymal stem cells reduce fibrosis of bleomycin-induced lung injury. Am J Pathol. 2009;175:303-13.
57. Zhao F, Zhang YF, Liu YG, Zhou JJ, Li ZK, Wu CG, et al. Therapeutic effects of bone marrow-derived mesenchymal stem cells engraftment on bleomycin-induced lung injury in rats. Transplant Proc. 2008;40:1700-5.
58. Ortiz LA, Dutreil M, Fattman C, Pandey AC, Torres G, Go K, et al. Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. Proc Natl Acad Sci U S A. 2007;104:11002-7.
59. Papadaki HA, Boumpas DT, Gibson FM, Jayne DR, Axford JS, Gordon-Smith EC, et al. Increased apoptosis of bone marrow CD34(+) cells and impaired function of bone marrow stromal cells in patients with systemic lupus erythematosus. Br J Haematol. 2001;115:167-74.
60. Nie Y, Lau C, Lie A, Chan G, Mok M. Defective phenotype of mesenchymal stem cells in patients with systemic lupus erythematosus. Lupus. 2010;19:850-9.
61. Sun LY, Zhang HY, Feng XB, Hou YY, Lu LW, Fan LM. Abnormality of bone marrow-derived mesenchymal stem cells in patients with systemic lupus erythematosus. Lupus. 2007;16:121-8.
62. Tang Y, Ma X, Zhang H, Gu Z, Hou Y, Gilkeson GS, et al. Gene expression profile reveals abnormalities of multiple signaling pathways in mesenchymal stem cell derived from patients with systemic lupus erythematosus. Clin Dev Immunol. 2012;2012:826182.
63. Gu Z, Cao X, Jiang J, Li L, Da Z, Liu H, et al. Upregulation of p16INK4A promotes cellular senescence of bone marrow-derived mesenchymal stem cells from systemic lupus erythematosus patients. Cell Signal. 2012;24:2307-14.
64. Gu Z, Tan W, Feng G, Meng Y, Shen B, Liu H, et al. Wnt/beta-catenin signaling mediates the senescence of bone marrow-mesenchymal stem cells from systemic lupus erythematosus patients through the p53/p21 pathway. Mol Cell Biochem. 2014;387:27-37.
65. Li X, Liu L, Meng D, Wang D, Zhang J, Shi D, et al. Enhanced apoptosis and senescence of bone-marrow-derived mesenchymal stem cells in patients with systemic lupus erythematosus. Stem Cells Dev. 2012;21:2387-94.
66. Del Papa N, Quirici N, Soligo D, Scavullo C, Cortiana M, Borsotti C, et al. Bone marrow endothelial progenitors are defective in systemic sclerosis. Arthritis Rheum. 2006;54:2605-15.
67. Cipriani P, Guiducci S, Miniati I, Cinelli M, Urbani S, Marrelli A, et al. 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.
68. Cipriani P, Di Benedetto P, Liakouli V, Del Papa B, Di Padova M, Di Ianni M, et al. Mesenchymal stem cells (MSCs) from scleroderma patients (SSc) preserve their immunomodulatory properties although senescent and normally induce T regulatory cells (Tregs) with a functional phenotype: implications for cellular-based therapy. Clin Exp Immunol. 2013;173:195-206.
69. Larghero J, Farge D, Braccini A, Lecourt S, Scherberich A, Foïs E, et al. Phenotypical and functional characteristics of in vitro expanded bone marrow mesenchymal stem cells from patients with systemic sclerosis. Ann Rheum Dis. 2008;67:443-9.
70. Bocelli-Tyndall C, Bracci L, Spagnoli G, Braccini A, Bouchenaki M, Ceredig R, et al. Bone marrow mesenchymal stromal cells (BM-MSCs) from healthy donors and auto-immune disease patients reduce the proliferation of autologous- and allogeneic-stimulated lymphocytes in vitro. Rheumatology (Oxford). 2007;46:403-8.
71. Vanneaux V, Farge-Bancel D, Lecourt S, Baraut J, Cras A, Jean-Louis F, et al. Expression of transforming growth factor beta receptor II in mesenchymal stem cells from systemic sclerosis patients. BMJ Open. 2013;3. doi: 10.1136/bmjopen-2012-001890.
72. Ikehara S, Good RA, Nakamura T, Sekita K, Inoue S, Oo MM, et al. Rationale for bone marrow transplantation in the treatment of autoimmune diseases. Proc Natl Acad Sci U S A. 1985;82:2483-7.
73. van Bekkum DW. Experimental basis of hematopoietic stem cell transplantation for treatment of autoimmune diseases. J Leukoc Biol. 2002;72:609-20.
74. Tyndall A, Gratwohl A. Blood and marrow stem cell transplants in auto-immune disease: a consensus report written on behalf of the European League against Rheumatism (EULAR) and the European Group for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant. 1997;19:643-5.
75. Snowden JA, Saccardi R, Allez M, Ardizzone S, Arnold R, Cervera R, et al. Haematopoietic SCT in severe autoimmune diseases: updated guidelines of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant. 2012;47:770-90.
76. Farge D, Henegar C, Carmagnat M, Daneshpouy M, Marjanovic Z, Rabian C, et al. Analysis of immune reconstitution after autologous bone marrow transplantation in systemic sclerosis. Arthritis Rheum. 2005;52:1555-63.
77. Muraro PA, Douek DC, Packer A, Chung K, Guenaga FJ, Cassiani-Ingoni R, et al. Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients. J Exp Med. 2005;201:805-16.
78. Alexander T, Thiel A, Rosen O, Massenkeil G, Sattler A, Kohler S, et al. Depletion of autoreactive immunologic memory followed by autologous hematopoietic stem cell transplantation in patients with refractory SLE induces long-term remission through de novo generation of a juvenile and tolerant immune system. Blood. 2009;113:214-23.
79. Zhang L, Bertucci AM, Ramsey-Goldman R, Burt RK, Datta SK. Regulatory T cell (Treg) subsets return in patients with refractory lupus following stem cell transplantation, and TGF-beta-producing CD8+ Treg cells are associated with immunological remission of lupus. J Immunol. 2009;183:6346-58.
80. Bingham S, Veale D, Fearon U, Isaacs JD, Morgan G, Emery P, et al. High-dose cyclophosphamide with stem cell rescue for severe rheumatoid arthritis: short-term efficacy correlates with reduction of macroscopic and histologic synovitis. Arthritis Rheum. 2002;46:837-9.
81. Muraro PA, Douek DC. Renewing the T cell repertoire to arrest autoimmune aggression. Trends Immunol. 2006;27:61-7.
82. Le Blanc K, Rasmusson I, Sundberg B, Götherström C, Hassan M, Uzunel M, et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. 2004;363:1439-41.
83. Wang D, Zhang H, Liang J, Li X, Feng X, Wang H, et al. Allogeneic mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus: 4 years of experience. Cell Transplant. 2013;22:2267-77.
84. Sun L, Wang D, Liang J, Zhang H, Feng X, Wang H, et al. Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus. Arthritis Rheum. 2010;62:2467-75.
85. Shi D, Wang D, Li X, Zhang H, Che N, Lu Z, et al. Allogeneic transplantation of umbilical cord-derived mesenchymal stem cells for diffuse alveolar hemorrhage in systemic lupus erythematosus. Clin Rheumatol. 2012;31:841-6.
86. Li X, Wang D, Liang J, Zhang H, Sun L. Mesenchymal SCT ameliorates refractory cytopenia in patients with systemic lupus erythematosus. Bone Marrow Transplant. 2013;48:544-50.
87. Wang D, Li J, Zhang Y, Zhang M, Chen J, Li X, et al. Umbilical cord mesenchymal stem cell transplantation in active and refractory systemic lupus erythematosus: a multicenter clinical study. Arthritis Res Ther. 2014;16:R79.
88. Christopeit M, Schendel M, Föll J, Müller LP, Keysser G, Behre G. Marked improvement of severe progressive systemic sclerosis after transplantation of mesenchymal stem cells from an allogeneic haploidentical-related donor mediated by ligation of CD137L. Leukemia. 2008;22:1062-4.
89. Keyszer G, Christopeit M, Fick S, Schendel M, Taute BM, Behre G, et al. Treatment of severe progressive systemic sclerosis with transplantation of mesenchymal stromal cells from allogeneic related donors: report of five cases. Arthritis Rheum. 2011;63:2540-2.