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Stem Cell Therapy for GVHD

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Stem Cells: Basics and Clinical Translation

Part of the book series: Translational Medicine Research ((TRAMERE,volume 1))

Abstract

Graft-versus-host disease (GVHD) is a major complication associated with morbidity and mortality following allogeneic hematopoietic stem cell transplantation (HSCT). GVHD can be fatal, as patients frequently fail to respond to conventional immunosuppressants and no established second-line therapy is available. Stem cells have emerged as a therapeutic approach in a range of medical fields, including regenerative medicine, cancer, autoimmune diseases, and inflammatory diseases, because of their unique properties. In particular, mesenchymal stem cells (MSCs) have created increasing interest as a therapeutic agent for various immune-mediated diseases including GVHD. MSCs demonstrate therapeutic potential by exerting potent immunosuppressive effects through interactions between lymphocytes associated with both the innate and adaptive immune system. Preclinical experiments using MSCs for the treatment of GVHD have provided critical insights into the mechanism of action of MSCs and evidence for clinical translation. In the clinical setting, Ringden’s pilot study using MSCs to treat a steroid-refractory GVHD pediatric patient was a milestone in the field of MSC therapy, which leads to numerous worldwide studies on steroid-refractory GVHD, de novo GVHD, chronic GVHD treatment, and GVHD prevention. In this chapter, we focus on the recent advances of MSCs for the treatment of GVHD in both preclinical and clinical settings. We discuss the current limitations and highlight the future considerations that should be made when using stem cell therapy for GVHD.

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Notes

  1. 1.

    Osiris Therapeutics Inc. Products. Osiris Therapeutics Inc.

  2. 2.

    Athersys I MultiStem: a novel stem cell therapy. Athersys, Inc.

References

  • Badillo AT, Peranteau WH, Heaton TE, Quinn C, Flake AW. Murine bone marrow derived stromal progenitor cells fail to prevent or treat acute graft-versus-host disease. Br J Haematol. 2008;141:224–34.

    Article  PubMed  Google Scholar 

  • Bai L, Lennon DP, Eaton V, Maier K, Caplan AI, Miller SD, Miller RH. Human bone marrow-derived mesenchymal stem cells induce Th2-polarized immune response and promote endogenous repair in animal models of multiple sclerosis. Glia. 2009;57:1192–203.

    Article  PubMed Central  PubMed  Google Scholar 

  • Baron F, Lechanteur C, Willems E, Bruck F, Baudoux E, Seidel L, Vanbellinghen JF, Hafraoui K, Lejeune M, Gothot A, Fillet G, Beguin Y. 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. 2010;16:838–47.

    Article  PubMed  Google Scholar 

  • Batten P, Sarathchandra P, Antoniw JW, Tay SS, Lowdell MW, Taylor PM, Yacoub MH. 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;12:2263–73.

    Article  CAS  PubMed  Google Scholar 

  • Beres A, Komorowski R, Mihara M, Drobyski WR. Instability of Foxp3 expression limits the ability of induced regulatory T cells to mitigate graft versus host disease. Clin Cancer Res. 2011;17:3969–83.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bernardo ME, Zaffaroni N, Novara F, Cometa AM, Avanzini MA, Moretta A, Montagna D, Maccario R, Villa R, Daidone MG, Zuffardi O, Locatelli F. Human bone marrow derived mesenchymal stem cells do not undergo transformation after long-term in vitro culture and do not exhibit telomere maintenance mechanisms. Cancer Res. 2007;67:9142–9.

    Article  CAS  PubMed  Google Scholar 

  • Boozer S, Lehman N, Lakshmipathy U, Love B, Raber A, Maitra A, Deans R, Rao MS, Ting AE. Global characterization and genomic stability of human multistem, a multipotent adult progenitor cell. J Stem Cells. 2009;4:17–28.

    PubMed  Google Scholar 

  • Bruck F, Belle L, Lechanteur C, de Leval L, Hannon M, Dubois S, Castermans E, Humblet-Baron S, Rahmouni S, Beguin Y, Briquet A, Baron F. Impact of bone marrow-derived mesenchymal stromal cells on experimental xenogeneic graft-versus-host disease. Cytotherapy. 2013;15:267–79.

    Article  CAS  PubMed  Google Scholar 

  • Brunstein CG, Miller JS, Cao Q, McKenna DH, Hippen KL, Curtsinger J, Defor T, Levine BL, June CH, Rubinstein P, McGlave PB, Blazar BR, Wagner JE. Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics. Blood. 2011;117:1061–70.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Burr SP, Dazzi F, Garden OA. Mesenchymal stromal cells and regulatory T cells: the Yin and Yang of peripheral tolerance? Immunol Cell Biol. 2013;91:12–8.

    Article  CAS  PubMed  Google Scholar 

  • Cahn JY, Klein JP, Lee SJ, Milpied N, Blaise D, Antin JH, Leblond V, Ifrah N, Jouet JP, Loberiza F, Ringden O, Barrett AJ, Horowitz MM, Socie G, Societe Francaise de Greffe de Moelle et Therapie Cellulaire, Dana Farber Cancer Institute, International Bone Marrow Transplant Registry. Prospective evaluation of 2 acute graft-versus-host (GVHD) grading systems: a joint Societe Francaise de Greffe de Moelle et Therapie Cellulaire (SFGM-TC), Dana Farber Cancer Institute (DFCI), and International Bone Marrow Transplant Registry (IBMTR) prospective study. Blood. 2005;106:1495–500.

    Google Scholar 

  • Chapel A, Bertho JM, Bensidhoum M, Fouillard L, Young RG, Frick J, Demarquay C, Cuvelier F, Mathieu E, Trompier F, Dudoignon N, Germain C, Mazurier C, Aigueperse J, Borneman J, Gorin NC, 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;5:1028–38.

    Article  PubMed  Google Scholar 

  • Chen L, Tredget EE, Wu PY, Wu Y. Paracrine factors of mesenchymal stem cells recruit macrophages and endothelial lineage cells and enhance wound healing. PLoS ONE. 2008;3:e1886.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Chen B, Hu J, Liao L, Sun Z, Han Q, Song Z, Zhao RC. Flk-1+ mesenchymal stem cells aggravate collagen-induced arthritis by up-regulating interleukin-6. Clin Exp Immunol. 2010;159:292–302.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Choi H, Lee RH, Bazhanov N, Oh JY, Prockop DJ. Anti-inflammatory protein TSG-6 secreted by activated MSCs attenuates zymosan-induced mouse peritonitis by decreasing TLR2/NF-kappaB signaling in resident macrophages. Blood. 2011;118:330–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Choi YS, Jeong JA, Lim DS. Mesenchymal stem cell-mediated immature dendritic cells induce regulatory T cell-based immunosuppressive effect. Immunol Invest. 2012;41:214–29.

    Article  CAS  PubMed  Google Scholar 

  • Chung NG, Jeong DC, Park SJ, Choi BO, Cho B, Kim HK, Chun CS, Won JH, Han CW. Cotransplantation of marrow stromal cells may prevent lethal graft-versus-host disease in major histocompatibility complex mismatched murine hematopoietic stem cell transplantation. Int J Hematol. 2004;80:370–6.

    Article  PubMed  Google Scholar 

  • Cohen JL, Trenado A, Vasey D, Klatzmann D, Salomon BL. CD4(+)CD25(+) immunoregulatory T Cells: new therapeutics for graft-versus-host disease. J Exp Med. 2002;196:401–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Comoli P, Ginevri F, Maccario R, Avanzini MA, 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;23:1196–202.

    Article  CAS  PubMed  Google Scholar 

  • Corcione A, Benvenuto F, Ferretti E, Giunti D, Cappiello V, Cazzanti F, Risso M, Gualandi F, Mancardi GL, Pistoia V, Uccelli A. Human mesenchymal stem cells modulate B-cell functions. Blood. 2006;107:367–72.

    Article  CAS  PubMed  Google Scholar 

  • Dazzi F, Marelli-Berg FM. Mesenchymal stem cells for graft-versus-host disease: close encounters with T cells. Eur J Immunol. 2008;38:1479–82.

    Article  CAS  PubMed  Google Scholar 

  • Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P, Grisanti S, Gianni AM. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood. 2002;99:3838–43.

    Article  PubMed  Google Scholar 

  • Djouad F, Plence P, Bony C, Tropel P, Apparailly F, Sany J, Noel D, Jorgensen C. Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood. 2003;102:3837–44.

    Article  CAS  PubMed  Google Scholar 

  • Djouad F, Charbonnier LM, 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;25:2025–32.

    Article  CAS  PubMed  Google Scholar 

  • Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8:315–7.

    Article  CAS  PubMed  Google Scholar 

  • Duffy MM, Pindjakova J, Hanley SA, McCarthy C, Weidhofer GA, Sweeney EM, English K, Shaw G, Murphy JM, Barry FP, Mahon BP, Belton O, Ceredig R, Griffin MD. Mesenchymal stem cell inhibition of T-helper 17 cell- differentiation is triggered by cell-cell contact and mediated by prostaglandin E2 via the EP4 receptor. Eur J Immunol. 2011;41:2840–51.

    Article  CAS  PubMed  Google Scholar 

  • Edinger M, Hoffmann P, Ermann J, Drago K, Fathman CG, Strober S, Negrin RS. CD4+ CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation. Nat Med. 2003;9:1144–50.

    Article  CAS  PubMed  Google Scholar 

  • Eljaafari A, Tartelin ML, Aissaoui H, Chevrel G, Osta B, Lavocat F, Miossec P. Bone marrow-derived and synovium-derived mesenchymal cells promote Th17 cell expansion and activation through caspase 1 activation: contribution to the chronicity of rheumatoid arthritis. Arthritis Rheum. 2012;64:2147–57.

    Article  CAS  PubMed  Google Scholar 

  • Engela AU, Baan CC, Peeters AM, Weimar W, Hoogduijn MJ. Interaction between adipose tissue-derived mesenchymal stem cells and regulatory T-cells. Cell Transplant. 2013;22:41–54.

    Article  PubMed  Google Scholar 

  • English K, Barry FP, Mahon BP. Murine mesenchymal stem cells suppress dendritic cell migration, maturation and antigen presentation. Immunol Lett. 2008;115:50–8.

    Article  CAS  PubMed  Google Scholar 

  • English K, Ryan JM, Tobin L, Murphy MJ, Barry FP, Mahon BP. Cell contact, prostaglandin E(2) and transforming growth factor beta 1 play non-redundant roles in human mesenchymal stem cell induction of CD4+ CD25(High) forkhead box P3+ regulatory T cells. Clin Exp Immunol. 2009;156:149–60.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fang B, Song YP, Liao LM, Han Q, Zhao RC. Treatment of severe therapy-resistant acute graft-versus-host disease with human adipose tissue-derived mesenchymal stem cells. Bone Marrow Transplant. 2006;38:389–90.

    Article  CAS  PubMed  Google Scholar 

  • Galipeau J. The mesenchymal stromal cells dilemma–does a negative phase III trial of random donor mesenchymal stromal cells in steroid-resistant graft-versus-host disease represent a death knell or a bump in the road? Cytotherapy. 2013;15:2–8.

    Article  PubMed  Google Scholar 

  • Ghannam S, Pene J, Moquet-Torcy G, Jorgensen C, Yssel H. Mesenchymal stem cells inhibit human Th17 cell differentiation and function and induce a T regulatory cell phenotype. J Immunol. 2010;185:302–12.

    Article  CAS  PubMed  Google Scholar 

  • Gore A, Li Z, Fung HL, Young JE, Agarwal S, Antosiewicz-Bourget J, Canto I, Giorgetti A, Israel MA, Kiskinis E, Lee JH, Loh YH, Manos PD, Montserrat N, Panopoulos AD, Ruiz S, Wilbert ML, Yu J, Kirkness EF, Izpisua Belmonte JC, Rossi DJ, Thomson JA, Eggan K, Daley GQ, Goldstein LS, Zhang K. Somatic coding mutations in human induced pluripotent stem cells. Nature. 2011;471:63–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Guo Z, Zheng C, Chen Z, Gu D, Du W, Ge J, Han Z, Yang R. Fetal BM-derived mesenchymal stem cells promote the expansion of human Th17 cells, but inhibit the production of Th1 cells. Eur J Immunol. 2009;39:2840–9.

    Article  CAS  PubMed  Google Scholar 

  • Highfill SL, Kelly RM, O’Shaughnessy MJ, Zhou Q, Xia L, Panoskaltsis-Mortari A, Taylor PA, Tolar J, Blazar BR. Multipotent adult progenitor cells can suppress graft-versus-host disease via prostaglandin E2 synthesis and only if localized to sites of allopriming. Blood. 2009;114:693–701.

    Google Scholar 

  • Hoffmann P, Ermann J, Edinger M, Fathman CG, Strober S. Donor-type CD4(+)CD25(+) regulatory T cells suppress lethal acute graft-versus-host disease after allogeneic bone marrow transplantation. J Exp Med. 2002;196:389–99.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hoogduijn MJ, Popp F, Verbeek R, Masoodi M, Nicolaou A, Baan C, Dahlke MH. The immunomodulatory properties of mesenchymal stem cells and their use for immunotherapy. Int Immunopharmacol. 2010;10:1496–500.

    Article  CAS  PubMed  Google Scholar 

  • Im KI, Park MJ, Kim N, Lim JY, Park HS, Lee SH, Nam YS, Lee ES, Lee JH, Cho ML, Cho SG. Induction of mixed chimerism using combinatory cell-based immune modulation with mesenchymal stem cells and regulatory T cells for solid-organ transplant tolerance. Stem Cells Dev. 2014.

    Google Scholar 

  • Jacobs SA, Pinxteren J, Roobrouck VD, Luyckx A, van’t Hof W, Deans R, Verfaillie CM, Waer M, Billiau AD, Van Gool SW. Human multipotent adult progenitor cells are nonimmunogenic and exert potent immunomodulatory effects on alloreactive T-cell responses. Cell Transplant. 2013;22:1915–28.

    Google Scholar 

  • Jacobs SA, Roobrouck VD, Verfaillie CM, Van Gool SW. Immunological characteristics of human mesenchymal stem cells and multipotent adult progenitor cells. Immunol Cell Biol. 2013;91:32–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jagasia M, Arora M, Flowers ME, Chao NJ, McCarthy PL, Cutler CS, Urbano-Ispizua A, Pavletic SZ, Haagenson MD, Zhang MJ, Antin JH, Bolwell BJ, Bredeson C, Cahn JY, Cairo M, Gale RP, Gupta V, Lee SJ, Litzow M, Weisdorf DJ, Horowitz MM, Hahn T. Risk factors for acute GVHD and survival after hematopoietic cell transplantation. Blood. 2012;119:296–307.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jang YK, Kim M, Lee YH, Oh W, Yang YS, Choi SJ. Optimization of the therapeutic efficacy of human umbilical cord blood-mesenchymal stromal cells in an NSG mouse xenograft model of graft-versus-host disease. Cytotherapy. 2014;16:298–308.

    Article  CAS  PubMed  Google Scholar 

  • Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature. 2002;418:41–9.

    Article  CAS  PubMed  Google Scholar 

  • Joo SY, Cho KA, Jung YJ, Kim HS, Park SY, Choi YB, Hong KM, Woo SY, Seoh JY, Cho SJ, Ryu KH. Mesenchymal stromal cells inhibit graft-versus-host disease of mice in a dose-dependent manner. Cytotherapy. 2010;12:361–70.

    Article  CAS  PubMed  Google Scholar 

  • Joo SY, Cho KA, Jung YJ, Kim HS, Park SY, Choi YB, Hong KM, Woo SY, Seoh JY, Ryu KH. Bioimaging for the monitoring of the in vivo distribution of infused mesenchymal stem cells in a mouse model of the graft-versus-host reaction. Cell Biol Int. 2011;35:417–21.

    Article  PubMed  Google Scholar 

  • Jung Y, Bauer G, Nolta JA. Concise review: Induced pluripotent stem cell-derived mesenchymal stem cells: progress toward safe clinical products. Stem Cells. 2012;30:42–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, Richardson AL, Polyak K, Tubo R, Weinberg RA. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 2007;449:557–63.

    Article  CAS  PubMed  Google Scholar 

  • Karp JM, Leng Teo GS. Mesenchymal stem cell homing: the devil is in the details. Cell Stem Cell. 2009;4:206–16.

    Google Scholar 

  • Keating A. How do mesenchymal stromal cells suppress T cells? Cell Stem Cell. 2008;2:106–8.

    Article  CAS  PubMed  Google Scholar 

  • Kebriaei P, Isola L, Bahceci E, Holland K, Rowley S, McGuirk J, Devetten M, Jansen J, Herzig R, Schuster M, Monroy R, Uberti J. Adult human mesenchymal stem cells added to corticosteroid therapy for the treatment of acute graft-versus-host disease. Biol Blood Marrow Transplant. 2009;15:804–11.

    Article  CAS  PubMed  Google Scholar 

  • Kim N, Cho SG. Clinical applications of mesenchymal stem cells. Korean J Intern Med. 2013;28:387–402.

    Article  PubMed Central  PubMed  Google Scholar 

  • Kim J, Hematti P. Mesenchymal stem cell-educated macrophages: a novel type of alternatively activated macrophages. Exp Hematol. 2009;37:1445–53.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kim N, Im KI, Lim JY, Jeon EJ, Nam YS, Kim EJ, Cho SG. Mesenchymal stem cells for the treatment and prevention of graft-versus-host disease: experiments and practice. Ann Hematol. 2013a;92:1295–308.

    Article  CAS  PubMed  Google Scholar 

  • Kim EJ, Kim N, Cho SG. The potential use of mesenchymal stem cells in hematopoietic stem cell transplantation. Exp Mol Med. 2013b;45:e2.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Kovacsovics-Bankowski M, Mauch K, Raber A, Streeter PR, Deans RJ, Maziarz RT, Van’t Hof W. Pre-clinical safety testing supporting clinical use of allogeneic multipotent adult progenitor cells. Cytotherapy. 2008;10:730–42.

    Google Scholar 

  • Kovacsovics-Bankowski M, Streeter PR, Mauch KA, Frey MR, Raber A, van’t Hof W, Deans R, Maziarz RT. Clinical scale expanded adult pluripotent stem cells prevent graft-versus-host disease. Cell Immunol. 2009;255:55–60.

    Google Scholar 

  • 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;101:3722–9.

    Article  CAS  PubMed  Google Scholar 

  • 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;24:386–98.

    Article  CAS  PubMed  Google Scholar 

  • Kuzmina LA, Petinati NA, Parovichnikova EN, Lubimova LS, Gribanova EO, Gaponova TV, Shipounova IN, Zhironkina OA, Bigildeev AE, Svinareva DA, Drize NJ, Savchenko VG. Multipotent mesenchymal stromal cells for the prophylaxis of acute graft-versus-host disease-A phase II study. Stem Cells Int. 2012;2012:968213.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Lazarus HM, Koc ON, Devine SM, Curtin P, Maziarz RT, Holland HK, Shpall EJ, McCarthy P, Atkinson K, Cooper BW, Gerson SL, Laughlin MJ, Loberiza FR Jr, Moseley AB, 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;11:389–98.

    Article  PubMed  Google Scholar 

  • Le Blanc K, Tammik C, Rosendahl K, Zetterberg E, Ringden O. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol. 2003a;31:890–6.

    Article  PubMed  CAS  Google Scholar 

  • Le Blanc K, Tammik L, Sundberg B, Haynesworth SE, Ringden O. Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand J Immunol. 2003b;57:11–20.

    Article  PubMed  Google Scholar 

  • Le Blanc K, Rasmusson I, Sundberg B, Gotherstrom C, Hassan M, Uzunel M, Ringden O. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. 2004;363:1439–41.

    Article  PubMed  Google Scholar 

  • Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, Sundberg B, Bernardo ME, Remberger M, Dini G, Egeler RM, Bacigalupo A, Fibbe W, Ringden O, Developmental Committee of the European Group for Blood and Marrow Transplantation. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008;371:1579–86.

    Google Scholar 

  • Lee JH, Jeon EJ, Kim N, Nam YS, Im KI, Lim JY, Kim EJ, Cho ML, Han KT, Cho SG. The synergistic immunoregulatory effects of culture-expanded mesenchymal stromal cells and CD4(+)25(+)Foxp3+ regulatory T cells on skin allograft rejection. PLoS ONE. 2013;8:e70968.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lepperdinger G, Brunauer R, Jamnig A, Laschober G, Kassem M. Controversial issue: is it safe to employ mesenchymal stem cells in cell-based therapies? Exp Gerontol. 2008;43:1018–23.

    Article  CAS  PubMed  Google Scholar 

  • Li YP, Paczesny S, Lauret E, Poirault S, Bordigoni P, Mekhloufi F, Hequet O, Bertrand Y, Ou-Yang JP, Stoltz JF, Miossec P, Eljaafari A. Human mesenchymal stem cells license adult CD34+ hemopoietic progenitor cells to differentiate into regulatory dendritic cells through activation of the Notch pathway. J Immunol. 2008a;180:1598–608.

    Article  CAS  PubMed  Google Scholar 

  • Li H, Guo Z, Jiang X, Zhu H, Li X, Mao N. Mesenchymal stem cells alter migratory property of T and dendritic cells to delay the development of murine lethal acute graft-versus-host disease. Stem Cells. 2008b;26:2531–41.

    Article  CAS  PubMed  Google Scholar 

  • Li H, Jiang Y, Jiang X, Guo X, Ning H, Li Y, Liao L, Yao H, Wang X, Liu Y, Zhang Y, Chen H, Mao N. CCR7 guides migration of mesenchymal stem cell to secondary lymphoid organs: a novel approach to separate GvHD from GvL effect. Stem Cells. 2014;32:1890–903.

    Article  CAS  PubMed  Google Scholar 

  • Lian Q, Zhang Y, Zhang J, Zhang HK, Wu X, Zhang Y, Lam FF, Kang S, Xia JC, Lai WH, Au KW, Chow YY, Siu CW, Lee CN, Tse HF. Functional mesenchymal stem cells derived from human induced pluripotent stem cells attenuate limb ischemia in mice. Circulation. 2010;121:1113–23.

    Article  PubMed  Google Scholar 

  • Lim JY, Park MJ, Im KI, Kim N, Jeon EJ, Kim EJ, Cho ML, Cho SG. Combination cell therapy using mesenchymal stem cells and regulatory T-cells provides a synergistic immunomodulatory effect associated with reciprocal regulation of TH1/TH2 and th17/treg cells in a murine acute graft-versus-host disease model. Cell Transplant. 2014;23:703–14.

    Article  PubMed  Google Scholar 

  • 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 ML, 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;26:279–89.

    Article  CAS  PubMed  Google Scholar 

  • Liu X, Qu X, Chen Y, Liao L, Cheng K, Shao C, Zenke M, Keating A, Zhao RC. Mesenchymal stem/stromal cells induce the generation of novel IL-10-dependent regulatory dendritic cells by SOCS3 activation. J Immunol. 2012;189:1182–92.

    Article  CAS  PubMed  Google Scholar 

  • Lucchini G, Introna M, Dander E, Rovelli A, Balduzzi A, Bonanomi S, Salvade A, Capelli C, Belotti D, Gaipa G, Perseghin P, Vinci P, Lanino E, Chiusolo P, Orofino MG, Marktel S, Golay J, Rambaldi A, Biondi A, D’Amico G, Biagi E. 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. 2010;16:1293–301.

    Article  PubMed  Google Scholar 

  • 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;90:516–25.

    CAS  PubMed  Google Scholar 

  • Madec AM, Mallone R, Afonso G, Abou Mrad E, Mesnier A, Eljaafari A, Thivolet C. Mesenchymal stem cells protect NOD mice from diabetes by inducing regulatory T cells. Diabetologia. 2009;52:1391–9.

    Article  CAS  PubMed  Google Scholar 

  • Maggini J, Mirkin G, Bognanni I, Holmberg J, Piazzon IM, Nepomnaschy I, Costa H, Canones C, Raiden S, Vermeulen M, Geffner JR. Mouse bone marrow-derived mesenchymal stromal cells turn activated macrophages into a regulatory-like profile. PLoS ONE. 2010;5:e9252.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Marigo I, Dazzi F. The immunomodulatory properties of mesenchymal stem cells. Semin Immunopathol. 2011;33:593–602.

    Article  PubMed  Google Scholar 

  • Martin PJ, Uberti JP, Soiffer RJ, Klingemann H, Waller EK, Daly AS, Herrmann RP, Kebriaei P. 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: J Am Soc Blood Marrow Transplant. 2010;16:S169–70.

    Article  Google Scholar 

  • 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;103:4619–21.

    Article  CAS  PubMed  Google Scholar 

  • Min CK, Kim BG, Park G, Cho B, Oh IH. IL-10-transduced bone marrow mesenchymal stem cells can attenuate the severity of acute graft-versus-host disease after experimental allogeneic stem cell transplantation. Bone Marrow Transplant. 2007;39:637–45.

    Article  CAS  PubMed  Google Scholar 

  • Muller I, Kordowich S, Holzwarth C, Isensee G, Lang P, Neunhoeffer F, Dominici M, Greil J, Handgretinger R. Application of multipotent mesenchymal stromal cells in pediatric patients following allogeneic stem cell transplantation. Blood Cells Mol Dis. 2008;40:25–32.

    Article  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Nemeth K, Leelahavanichkul A, Yuen PS, Mayer B, Parmelee A, Doi K, Robey PG, Leelahavanichkul K, Koller BH, Brown JM, Hu X, Jelinek I, Star RA, Mezey E. Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat Med. 2009;15:42–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ning H, Yang F, Jiang M, Hu L, Feng K, Zhang J, Yu Z, Li B, Xu C, Li Y, Wang J, Hu J, Lou X, Chen H. The correlation between cotransplantation of mesenchymal stem cells and higher recurrence rate in hematologic malignancy patients: outcome of a pilot clinical study. Leukemia. 2008;22:593–9.

    Article  CAS  PubMed  Google Scholar 

  • Okita K, Ichisaka T, Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature. 2007;448:313–7.

    Article  CAS  PubMed  Google Scholar 

  • Olson JA, Leveson-Gower DB, Gill S, Baker J, Beilhack A, Negrin RS. NK cells mediate reduction of GVHD by inhibiting activated, alloreactive T cells while retaining GVT effects. Blood. 2010;115:4293–301.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Park MJ, Park HS, Cho ML, Oh HJ, Cho YG, Min SY, Chung BH, Lee JW, Kim HY, Cho SG. Transforming growth factor beta-transduced mesenchymal stem cells ameliorate experimental autoimmune arthritis through reciprocal regulation of Treg/Th17 cells and osteoclastogenesis. Arthritis Rheum. 2011;63:1668–80.

    Article  CAS  PubMed  Google Scholar 

  • Patel SA, Meyer JR, Greco SJ, Corcoran KE, Bryan M, Rameshwar P. Mesenchymal stem cells protect breast cancer cells through regulatory T cells: role of mesenchymal stem cell-derived TGF-beta. J Immunol. 2010;184:5885–94.

    Article  CAS  PubMed  Google Scholar 

  • Payne NL, Dantanarayana A, Sun G, Moussa L, Caine S, McDonald C, Herszfeld D, Bernard CC, Siatskas C. Early intervention with gene-modified mesenchymal stem cells overexpressing interleukin-4 enhances anti-inflammatory responses and functional recovery in experimental autoimmune demyelination. Cell Adh Migr. 2012;6:179–89.

    Article  PubMed Central  PubMed  Google Scholar 

  • Polchert D, Sobinsky J, Douglas G, Kidd M, Moadsiri A, Reina E, Genrich K, Mehrotra S, Setty S, Smith B, Bartholomew A. IFN-gamma activation of mesenchymal stem cells for treatment and prevention of graft versus host disease. Eur J Immunol. 2008;38:1745–55.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Prasad VK, Lucas KG, Kleiner GI, Talano JA, Jacobsohn D, Broadwater G, Monroy R, Kurtzberg J. 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. 2011;17:534–41.

    Article  CAS  PubMed  Google Scholar 

  • Prigozhina TB, Khitrin S, Elkin G, Eizik O, Morecki S, Slavin S. Mesenchymal stromal cells lose their immunosuppressive potential after allotransplantation. Exp Hematol. 2008;36:1370–6.

    Article  CAS  PubMed  Google Scholar 

  • Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. 1994 Consensus conference on acute GVHD grading. Bone Marrow Transplant. 1995;15:825–8.

    Google Scholar 

  • Rasmusson I, Le Blanc K, Sundberg B, Ringden O. Mesenchymal stem cells stimulate antibody secretion in human B cells. Scand J Immunol. 2007;65:336–43.

    Article  CAS  PubMed  Google Scholar 

  • Ren G, Zhang L, Zhao X, Xu G, Zhang Y, Roberts AI, Zhao RC, Shi Y. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell. 2008;2:141–50.

    Article  CAS  PubMed  Google Scholar 

  • Resnick IB, Barkats C, Shapira MY, Stepensky P, Bloom AI, Shimoni A, Mankuta D, Varda-Bloom N, Rheingold L, Yeshurun M, Bielorai B, Toren A, Zuckerman T, Nagler A, Or R. Treatment of severe steroid-resistant acute GVHD with mesenchymal stromal cells (MSC). Am J Blood Res. 2013;3:225–38.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ringden O, Uzunel M, Rasmusson I, Remberger M, Sundberg B, Lonnies H, Marschall HU, 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;81:1390–7.

    Article  PubMed  Google Scholar 

  • Roobrouck VD, Clavel C, Jacobs SA, Ulloa-Montoya F, Crippa S, Sohni A, Roberts SJ, Luyten FP, Van Gool SW, Sampaolesi M, Delforge M, Luttun A, Verfaillie CM. Differentiation potential of human postnatal mesenchymal stem cells, mesoangioblasts, and multipotent adult progenitor cells reflected in their transcriptome and partially influenced by the culture conditions. Stem Cells. 2011;29:871–82.

    Article  CAS  PubMed  Google Scholar 

  • Rubtsov YP, Niec RE, Josefowicz S, Li L, Darce J, Mathis D, Benoist C, Rudensky AY. Stability of the regulatory T cell lineage in vivo. Science. 2010;329:1667–71.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A, Posati S, Rogaia D, Frassoni F, Aversa F, Martelli MF, Velardi A. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002;295:2097–100.

    Article  CAS  PubMed  Google Scholar 

  • Schena F, Gambini C, Gregorio A, Mosconi M, Reverberi D, Gattorno M, Casazza S, Uccelli A, Moretta L, Martini A, Traggiai E. 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.

    Article  CAS  PubMed  Google Scholar 

  • Sotiropoulou PA, Perez SA, Gritzapis AD, Baxevanis CN, Papamichail M. Interactions between human mesenchymal stem cells and natural killer cells. Stem Cells. 2006;24:74–85.

    Article  PubMed  Google Scholar 

  • Spaggiari GM, Capobianco A, Becchetti S, Mingari MC, 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;107:1484–90.

    Article  CAS  PubMed  Google Scholar 

  • Spaggiari GM, Capobianco A, Abdelrazik H, Becchetti F, Mingari MC, 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;111:1327–33.

    Article  CAS  PubMed  Google Scholar 

  • Spaggiari GM, Abdelrazik H, Becchetti F, Moretta L. MSCs inhibit monocyte-derived DC maturation and function by selectively interfering with the generation of immature DCs: central role of MSC-derived prostaglandin E2. Blood. 2009;113:6576–83.

    Article  CAS  PubMed  Google Scholar 

  • Stagg J, Galipeau J. Mechanisms of immune modulation by mesenchymal stromal cells and clinical translation. Curr Mol Med. 2013;13:856–67.

    Article  CAS  PubMed  Google Scholar 

  • Stagg J, Pommey S, Eliopoulos N, Galipeau J. Interferon-gamma-stimulated marrow stromal cells: a new type of nonhematopoietic antigen-presenting cell. Blood. 2006;107:2570–7.

    Article  CAS  PubMed  Google Scholar 

  • Sudres M, Norol F, Trenado A, Gregoire S, Charlotte F, Levacher B, Lataillade JJ, Bourin P, Holy X, Vernant JP, Klatzmann D, Cohen JL. Bone marrow mesenchymal stem cells suppress lymphocyte proliferation in vitro but fail to prevent graft-versus-host disease in mice. J Immunol. 2006;176:7761–7.

    Article  CAS  PubMed  Google Scholar 

  • 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;92:1208–15.

    Article  CAS  PubMed  Google Scholar 

  • Svobodova E, Krulova M, Zajicova A, Pokorna K, Prochazkova J, Trosan P, Holan V. The role of mouse mesenchymal stem cells in differentiation of naive T-cells into anti-inflammatory regulatory T-cell or proinflammatory helper T-cell 17 population. Stem Cells Dev. 2012;21:901–10.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663–76.

    Article  CAS  PubMed  Google Scholar 

  • Taylor PA, Lees CJ, Blazar BR. The infusion of ex vivo activated and expanded CD4(+)CD25(+) immune regulatory cells inhibits graft-versus-host disease lethality. Blood. 2002;99:3493–9.

    Article  CAS  PubMed  Google Scholar 

  • Teshima T. Th1 and Th17 join forces for acute GVHD. Blood. 2011;118:4765–7.

    Article  CAS  PubMed  Google Scholar 

  • Tisato V, Naresh K, Girdlestone J, Navarrete C, Dazzi F. Mesenchymal stem cells of cord blood origin are effective at preventing but not treating graft-versus-host disease. Leukemia. 2007;21:1992–9.

    Article  CAS  PubMed  Google Scholar 

  • Tolar J, Nauta AJ, Osborn MJ, Panoskaltsis Mortari A, McElmurry RT, Bell S, Xia L, Zhou N, Riddle M, Schroeder TM, Westendorf JJ, McIvor RS, Hogendoorn PC, Szuhai K, Oseth L, Hirsch B, Yant SR, Kay MA, Peister A, Prockop DJ, Fibbe WE, Blazar BR. Sarcoma derived from cultured mesenchymal stem cells. Stem Cells. 2007;25:371–9.

    Article  CAS  PubMed  Google Scholar 

  • 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;26:562–9.

    Article  CAS  PubMed  Google Scholar 

  • Vaes B, Van’t Hof W, Deans R, Pinxteren J. Application of Multistem® allogeneic cells for immunomodulatory therapy: clinical progress and pre-clinical challenges in prophylaxis for graft versus host disease. Front Immunol. 2012;3:345.

    Article  PubMed Central  PubMed  Google Scholar 

  • von Bonin M, Stolzel F, Goedecke A, Richter K, Wuschek N, Holig K, Platzbecker U, Illmer T, Schaich M, Schetelig J, Kiani A, Ordemann R, Ehninger G, Schmitz M, Bornhauser M. Treatment of refractory acute GVHD with third-party MSC expanded in platelet lysate-containing medium. Bone Marrow Transplant. 2009;43:245–51.

    Article  CAS  Google Scholar 

  • Wang Y, Huso DL, Harrington J, Kellner J, Jeong DK, Turney J, McNiece IK. Outgrowth of a transformed cell population derived from normal human BM mesenchymal stem cell culture. Cytotherapy. 2005;7:509–19.

    Article  CAS  PubMed  Google Scholar 

  • Waterman RS, Tomchuck SL, Henkle SL, Betancourt AM. A new mesenchymal stem cell (MSC) paradigm: polarization into a pro-inflammatory MSC1 or an Immunosuppressive MSC2 phenotype. PLoS ONE. 2010;5:e10088.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Weng JY, Du X, Geng SX, Peng YW, Wang Z, Lu ZS, Wu SJ, Luo CW, Guo R, Ling W, Deng CX, Liao PJ, Xiang AP. Mesenchymal stem cell as salvage treatment for refractory chronic GVHD. Bone Marrow Transplant. 2010;45:1732–40.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wu KH, Chan CK, Tsai C, Chang YH, Sieber M, Chiu TH, Ho M, Peng CT, Wu HP, Huang JL. Effective treatment of severe steroid-resistant acute graft-versus-host disease with umbilical cord-derived mesenchymal stem cells. Transplantation. 2011;91:1412–6.

    Article  PubMed  Google Scholar 

  • Yang H, Aprecio RM, Zhou X, Wang Q, Zhang W, Ding Y, Li Y. Therapeutic effect of TSG-6 engineered iPSC-derived MSCs on experimental periodontitis in rats: a pilot study. PLoS ONE. 2014;9:e100285.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • 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;106:1755–61.

    Article  CAS  PubMed  Google Scholar 

  • Zhang B, Liu R, Shi D, Liu X, Chen Y, Dou X, Zhu X, Lu C, Liang W, Liao L, Zenke M, Zhao RC. Mesenchymal stem cells induce mature dendritic cells into a novel Jagged-2-dependent regulatory dendritic cell population. Blood. 2009;113:46–57.

    Article  CAS  PubMed  Google Scholar 

  • Zhou H, Guo M, Bian C, Sun Z, Yang Z, Zeng Y, Ai H, Zhao RC. Efficacy of bone marrow-derived mesenchymal stem cells in the treatment of sclerodermatous chronic graft-versus-host disease: clinical report. Biol Blood Marrow Transplant. 2010;16:403–12.

    Article  CAS  PubMed  Google Scholar 

  • Zhu W, Xu W, Jiang R, Qian H, Chen M, Hu J, Cao W, Han C, Chen Y. Mesenchymal stem cells derived from bone marrow favor tumor cell growth in vivo. Exp Mol Pathol. 2006;80:267–74.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Institute for Translational Research and Molecular Imaging, The Catholic University of Korea College of Medicine, Seoul, Korea

    Nayoun Kim & Seok-Goo Cho

  2. Laboratory of Immune Regulation, Convergent Research Consortium for Immunologic Disease (CRCID), The Catholic University of Korea College of Medicine, Seoul, Korea

    Nayoun Kim & Seok-Goo Cho

  3. Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary’s Hospital, The Catholic University of Korea College of Medicine, #505, Banpo-Dong, Seocho-Ku, Seoul, 137-040, Korea

    Seok-Goo Cho

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  1. Center of Excellence in Tissue Engineeri, Institute of Basic Medical Sciences School of Basic Medicine, Beijing, China

    Robert Chunhua Zhao

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Kim, N., Cho, SG. (2015). Stem Cell Therapy for GVHD. In: Zhao, R. (eds) Stem Cells: Basics and Clinical Translation. Translational Medicine Research, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-7273-0_15

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