[en] Mesenchymal stromal cells (MSCs) have potent immunomodulatory properties that make them an attractive tool against graft- vs.-host disease (GVHD). However, despite promising results in phase I/II studies, bone marrow (BM-) derived MSCs failed to demonstrate their superiority over placebo in the sole phase III trial reported thus far. MSCs from different tissue origins display different characteristics, but their therapeutic benefits have never been directly compared in GVHD. Here, we compared the impact of BM-, umbilical cord (UC-), and adipose-tissue (AT-) derived MSCs on T-cell function in vitro and assessed their efficacy for the treatment of GVHD induced by injection of human peripheral blood mononuclear cells in NOD-scid IL-2Rgamma(null) HLA-A2/HHD mice. In vitro, resting BM- and AT-MSCs were more potent than UC-MSCs to inhibit lymphocyte proliferation, whereas UC- and AT-MSCs induced a higher regulatory T-cell (CD4(+)CD25(+)FoxP3(+))/T helper 17 ratio. Interestingly, AT-MSCs and UC-MSCs activated the coagulation pathway at a higher level than BM-MSCs. In vivo, AT-MSC infusions were complicated by sudden death in 4 of 16 animals, precluding an analysis of their efficacy. Intravenous MSC infusions (UC- or BM- combined) failed to significantly increase overall survival (OS) in an analysis combining data from 80 mice (hazard ratio [HR] = 0.59, 95% confidence interval [CI] 0.32-1.08, P = 0.087). In a sensitivity analysis we also compared OS in control vs. each MSC group separately. The results for the BM-MSC vs. control comparison was HR = 0.63 (95% CI 0.30-1.34, P = 0.24) while the figures for the UC-MSC vs. control comparison was HR = 0.56 (95% CI 0.28-1.10, P = 0.09). Altogether, these results suggest that MSCs from various origins have different effects on immune cells in vitro and in vivo. However, none significantly prevented death from GVHD. Finally, our data suggest that the safety profile of AT-MSC and UC-MSC need to be closely monitored given their pro-coagulant activities in vitro.
Veriter, Sophie; Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Laboratoire de thérapie cellulaire et génique (LTCG)
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Bibliography
Baron F, Storb R. Allogeneic hematopoietic cell transplantation as treatment for hematological malignancies: a review. Springer Semin Immunopathol. (2004) 26:71–94. doi: 10.1007/s00281-004-0165-3
Dickinson AM, Norden J, Li S, Hromadnikova I, Schmid C, Schmetzer H, et al. Graft- vs.leukemia effect following hematopoietic stem cell transplantation for leukemia. Front Immunol. (2017) 8:496. doi: 10.3389/fimmu.2017.00496
Bleakley M, Riddell SR. Molecules and mechanisms of the graft- vs.-leukaemia effect. Nat Rev Cancer. (2004) 4:371–80. doi: 10.1038/nrc1365
Blazar BR, Murphy WJ, Abedi M. Advances in graft-vs.-host disease biology and therapy. Nat Rev Immunol. (2012) 12:443–58. doi: 10.1038/nri3212
Ghimire S, Weber D, Mavin E, Wang XN, Dickinson AM, Holler E. Pathophysiology of GvHD and other HSCT-related major complications. Front Immunol. (2017) 8:79. doi: 10.3389/fimmu.2017.00079
Zeiser R, Socie G, Blazar BR. Pathogenesis of acute graft- vs.-host disease: from intestinal microbiota alterations to donor T cell activation. Br J Haematol. (2016) 175:191–207. doi: 10.1111/bjh.14295
Baron F, Labopin M, Niederwieser D, Vigouroux S, Cornelissen JJ, Malm C, et al. Impact of graft- vs.-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European group for blood and marrow transplantation. Leukemia. (2012) 26:2462–8. doi: 10.1038/leu.2012.135
Baron F, Ruggeri A, Beohou E, Labopin M, Mohty M, Sanz J, et al. Occurrence of graft- vs.-host disease increases mortality after umbilical cord blood transplantation for acute myeloid leukemia: a report from Eurocord and the ALWP of the EBMT. J Intern Med. (2018) 283:178–89. doi: 10.1111/joim.12696
Socie G, Vigouroux S, Yakoub-Agha I, Bay JO, Furst S, Bilger K, et al. A phase 3 randomized trial comparing inolimomab vs. usual care in steroid-resistant acute GVHD. Blood. (2017) 129:643–9. doi: 10.1182/blood-2016-09-738625
Dominici M, Le BK, 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. doi: 10.1080/14653240600855905
Le Blanc K, Mougiakakos D. Multipotent mesenchymal stromal cells and the innate immune system. Nat Rev Immunol. (2012) 12:383–96. doi: 10.1038/nri3209
Reis M, Ogonek J, Qesari M, Borges NM, Nicholson L, Preussner L, et al. Recent developments in cellular immunotherapy for HSCT-associated complications. Front Immunol. (2016) 7:500. doi: 10.3389/fimmu.2016.00500
Davies LC, Heldring N, Kadri N, Le Blanc K. Mesenchymal stromal cell secretion of programmed death-1 ligands regulates T cell mediated immunosuppression. Stem Cells. (2017) 35:766–76. doi: 10.1002/stem.2509
Baron F, Storb R. Mesenchymal stromal cells: a new tool against graft- vs.-host disease? Biol Blood Marrow Transplant. (2012) 18:822–40. doi: 10.1016/j.bbmt.2011.09.003
Zhang L, Yu J, Wei W. Advance in targeted immunotherapy for graft- vs.-host disease. Front Immunol. (2018) 9:1087. doi: 10.3389/fimmu.2018.01087
Blazar BR, MacDonald KPA, Hill GR. Immune regulatory cell infusion for graft- vs.-host disease prevention and therapy. Blood. (2018) 131:2651–60. doi: 10.1182/blood-2017-11-785865
Ball LM, Bernardo ME, Roelofs H, Lankester A, Cometa A, Egeler RM, et al. 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) 110:2764–7. doi: 10.1182/blood-2007-04-087056
Ning H, Yang F, Jiang M, Hu L, Feng K, Zhang J, et al. 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. doi: 10.1038/sj.leu.2405090
Baron F, Lechanteur C, Willems E, Bruck F, Baudoux E, Seidel L, et al. Cotransplantation of mesenchymal stem cells might prevent death from graft- vs.-host disease (GVHD) without abrogating graft- vs.-tumor effects after HLA-mismatched allogeneic transplantation following nonmyeloablative conditioning. Biol Blood Marrow Transpl. (2010) 16:838–47. doi: 10.1016/j.bbmt.2010.01.011
Kallekleiv M, Larun L, Bruserud O, Hatfield KJ. Co-transplantation of multipotent mesenchymal stromal cells in allogeneic hematopoietic stem cell transplantation: a systematic review and meta-analysis. Cytotherapy. (2016) 18:172–85. doi: 10.1016/j.jcyt.2015.11.010
Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, et al. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft- vs.-host disease: a phase II study. Lancet. (2008) 371:1579–86. doi: 10.1016/S0140-6736(08)60690-X
Chen X, Wang C, Yin J, Xu J, Wei J, Zhang Y. Efficacy of mesenchymal stem cell therapy for steroid-refractory acute graft- vs.-host disease following allogeneic hematopoietic stem cell transplantation: a systematic review and meta-analysis. PloS ONE. (2015) 10:e0136991. doi: 10.1371/journal.pone.0136991
Servais S, Baron F, Lechanteur C, Seidel L, Selleslag D, Maertens J, et al. Infusion of bone marrow derived multipotent mesenchymal stromal cells for the treatment of steroid-refractory acute graft- vs.-host disease: a multicenter prospective study. Oncotarget. (2018) 9:20590–604. doi: 10.18632/oncotarget.25020
Hashmi S, Ahmed M, Murad MH, Litzow MR, Adams RH, Ball LM, et al. Survival after mesenchymal stromal cell therapy in steroid-refractory acute graft- vs.-host disease: systematic review and meta-analysis. Lancet Haematol. (2016) 3:e45–52. doi: 10.1016/S2352-3026(15)00224-0
Martin PJ, Uberti JP, Soiffer RJ, Klingemann H, Waller EK, Daly AS, et al. Prochymal improves response rates in patients with steroid-refractory acute graft vs. host disease (SR-GVHD) involving the liver and gut: results of a randomized, placebo-controlled, multicenter phase III trial In GVHD. Biol Blood Marrow Transpl. (2010) 16 (Suppl. 2):S169–70. doi: 10.1016/j.bbmt.2009.12.057
Galipeau J, Sensebe L. Mesenchymal stromal cells: clinical challenges and therapeutic opportunities. Cell Stem Cell. (2018) 22:824–33. doi: 10.1016/j.stem.2018.05.004
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. doi: 10.1371/journal.pone.0010088
Mattar P, Bieback K. Comparing the immunomodulatory properties of bone marrow, adipose tissue, and birth-associated tissue mesenchymal stromal cells. Front Immunol. (2015) 6:560. doi: 10.3389/fimmu.2015.00560
Waldner M, Zhang W, James IB, Allbright K, Havis E, Bliley JM, et al. Characteristics and immunomodulating functions of adipose-derived and bone marrow-derived mesenchymal stem cells across defined human leukocyte antigen barriers. Front Immunol. (2018) 9:1642. doi: 10.3389/fimmu.2018.01642
Ehx G, Somja J, Warnatz HJ, Ritacco C, Hannon M, Delens L, et al. Xenogeneic graft- vs.-host disease in humanized NSG and NSG-HLA-A2/HHD mice. Front Immunol. (2018) 9:1943. doi: 10.3389/fimmu.2018.01943
Betts BC, Veerapathran A, Pidala J, Yang H, Horna P, Walton K, et al. Targeting aurora kinase A and JAK2 prevents GVHD while maintaining Treg and antitumor CTL function. Sci Transl Med. (2017) 9:eaai8269. doi: 10.1126/scitranslmed.aai8269
Lechanteur C, Briquet A, Giet O, Delloye O, Baudoux E, Beguin Y. Clinical-scale expansion of mesenchymal stromal cells: a large banking experience. J Transl Med. (2016) 14:145. doi: 10.1186/s12967-016-0892-y
Veriter S, Andre W, Aouassar N, Poirel HA, Lafosse A, Docquier PL, et al. Human adipose-derived mesenchymal stem cells in cell therapy: safety and feasibility in different “hospital exemption” clinical applications. PloS ONE. (2015) 10:e0139566. doi: 10.1371/journal.pone.0139566
Shultz LD, Saito Y, Najima Y, Tanaka S, Ochi T, Tomizawa M, et al. Generation of functional human T-cell subsets with HLA-restricted immune responses in HLA class I expressing NOD/SCID/IL2r gamma(null) humanized mice. Proc Natl Acad Sci USA. (2010) 107:13022–7. doi: 10.1073/pnas.1000475107
Hannon M, Lechanteur C, Lucas S, Somja J, Seidel L, Belle L, et al. Infusion of clinical-grade enriched regulatory T cells delays experimental xenogeneic graft- vs.-host disease. Transfusion. (2014) 54:353–63. doi: 10.1111/trf.12279
Delens L, Ehx G, Somja J, Vrancken L, Belle L, Seidel L, et al. In vitro Th17-polarized human CD4(+) T cells exacerbate xenogeneic graft- vs.-host disease. Biol Blood Marrow Transpl. (2018) 25:204–15. doi: 10.1016/j.bbmt.2018.10.007
Ryan JM, Barry F, Murphy JM, Mahon BP. Interferon-gamma does not break, but promotes the immunosuppressive capacity of adult human mesenchymal stem cells. Clin Exp Immunol. (2007) 149:353–63. doi: 10.1111/j.1365-2249.2007.03422.x
Polchert D, Sobinsky J, Douglas G, Kidd M, Moadsiri A, Reina E, et al. IFN-gamma activation of mesenchymal stem cells for treatment and prevention of graft vs. host disease. Eur J Immunol. (2008) 38:1745–55. doi: 10.1002/eji.200738129
Luk F, Carreras-Planella L, Korevaar SS, de Witte SFH, Borras FE, Betjes MGH, et al. Inflammatory conditions dictate the effect of mesenchymal stem or stromal cells on B cell function. Front Immunol. (2017) 8:1042. doi: 10.3389/fimmu.2017.01042
Yan L, Zheng D, Xu RH. Critical role of tumor necrosis factor signaling in mesenchymal stem cell-based therapy for autoimmune and inflammatory diseases. Front Immunol. (2018) 9:1658. doi: 10.3389/fimmu.2018.01658
Boland L, Burand AJ, Brown AJ, Boyt D, Lira VA, Ankrum JA. IFN-gamma and TNF-alpha pre-licensing protects mesenchymal stromal cells from the pro-inflammatory effects of palmitate. Mol Ther. (2018) 26:860–73. doi: 10.1016/j.ymthe.2017.12.013
Reddy M, Eirikis E, Davis C, Davis HM, Prabhakar U. Comparative analysis of lymphocyte activation marker expression and cytokine secretion profile in stimulated human peripheral blood mononuclear cell cultures: an in vitro model to monitor cellular immune function. J Immunol Methods. (2004) 293:127–42. doi: 10.1016/j.jim.2004.07.006
Bruck F, Belle L, Lechanteur C, De LL, Hannon M, Dubois S, et al. Impact of bone marrow-derived mesenchymal stromal cells on experimental xenogeneic graft- vs.-host disease. Cytotherapy. (2013) 15:267–79. doi: 10.1016/j.jcyt.2012.09.003
Moll G, Ignatowicz L, Catar R, Luecht C, Sadeghi B, Hamad O, et al. Different procoagulant activity of therapeutic mesenchymal stromal cells derived from bone marrow and placental decidua. Stem Cells Dev. (2015) 24:2269–79. doi: 10.1089/scd.2015.0120
Tatsumi K, Ohashi K, Matsubara Y, Kohori A, Ohno T, Kakidachi H, et al. Tissue factor triggers procoagulation in transplanted mesenchymal stem cells leading to thromboembolism. Biochem Biophys Res Commun. (2013) 431:203–9. doi: 10.1016/j.bbrc.2012.12.134
Sadeghi B, Heshmati Y, Khoein B, Kaipe H, Uzunel M, Walfridsson J, et al. Xeno-immunosuppressive properties of human decidual stromal cells in mouse models of alloreactivity in vitro and in vivo. Cytotherapy. (2015) 17:1732–45. doi: 10.1016/j.jcyt.2015.09.001
Le Blanc K, Rasmusson I, Sundberg B, Gotherstrom C, Hassan M, Uzunel M, et al. Treatment of severe acute graft- vs.-host disease with third party haploidentical mesenchymal stem cells. Lancet. (2004) 363:1439–41. doi: 10.1016/S0140-6736(04)16104-7
King MA, Covassin L, Brehm MA, Racki W, Pearson T, Leif J, et al. Human peripheral blood leucocyte non-obese diabetic-severe combined immunodeficiency interleukin-2 receptor gamma chain gene mouse model of xenogeneic graft- vs.-host-like disease and the role of host major histocompatibility complex. Clin Exp Immunol. (2009) 157:104–18. doi: 10.1111/j.1365-2249.2009.03933.x
Kanakry CG, Ganguly S, Zahurak M, Bolanos-Meade J, Thoburn C, Perkins B, et al. Aldehyde dehydrogenase expression drives human regulatory T cell resistance to posttransplantation cyclophosphamide. Sci Transl Med. (2013) 5:211ra157. doi: 10.1126/scitranslmed.3006960
Cuende J, Lienart S, Dedobbeleer O, van der Woning B, De Boeck G, Stockis J, et al. Monoclonal antibodies against GARP/TGF-beta1 complexes inhibit the immunosuppressive activity of human regulatory T cells in vivo. Sci Transl Med. (2015) 7:284ra56. doi: 10.1126/scitranslmed.aaa1983
Coman T, Rossignol J, D'Aveni M, Fabiani B, Dussiot M, Rignault R, et al. Human CD4-invariant NKT lymphocytes regulate graft vs. host disease. Oncoimmunology. (2018) 7:e1470735. doi: 10.1080/2162402X.2018.1470735
Ehx G, Fransolet G, de Leval L, D'Hondt S, Lucas S, Hannon M, et al. Azacytidine prevents experimental xenogeneic graft- vs.-host disease without abrogating graft- vs.-leukemia effects. Oncoimmunology. (2017) 6:e1314425. doi: 10.1080/2162402X.2017.1314425
Joo SY, Cho KA, Jung YJ, Kim HS, Park SY, Choi YB, et al. Mesenchymal stromal cells inhibit graft- vs.-host disease of mice in a dose-dependent manner. Cytotherapy. (2010) 12:361–70. doi: 10.3109/14653240903502712
Girdlestone J, Pido-Lopez J, Srivastava S, Chai J, Leaver N, Galleu A, et al. Enhancement of the immunoregulatory potency of mesenchymal stromal cells by treatment with immunosuppressive drugs. Cytotherapy. (2015) 17:1188–99. doi: 10.1016/j.jcyt.2015.05.009
Tobin LM, Healy ME, English K, Mahon BP. Human mesenchymal stem cells suppress donor CD4(+) T cell proliferation and reduce pathology in a humanized mouse model of acute graft-vs.-host disease. Clin Exp Immunol. (2013) 172:333–48. doi: 10.1111/cei.12056
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- vs.-host disease. Leukemia. (2007) 21:1992–9. doi: 10.1038/sj.leu.2404847
Gregoire-Gauthier J, Selleri S, Fontaine F, Dieng MM, Patey N, Despars G, et al. Therapeutic efficacy of cord blood-derived mesenchymal stromal cells for the prevention of acute graft- vs.host disease in a xenogenic mouse model. Stem Cells Dev. (2012) 21:1616–26. doi: 10.1089/scd.2011.0413
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- vs.-host disease. Cytotherapy. (2014) 16:298–308. doi: 10.1016/j.jcyt.2013.10.012
Kim DS, Lee MW, Ko YJ, Park HJ, Park YJ, Kim DI, et al. Application of human mesenchymal stem cells cultured in different oxygen concentrations for treatment of graft- vs.-host disease in mice. Biomed Res. (2016) 37:311–7. doi: 10.2220/biomedres.37.311
Amarnath S, Foley JE, Farthing DE, Gress RE, Laurence A, Eckhaus MA, et al. Bone marrow-derived mesenchymal stromal cells harness purinergenic signaling to tolerize human Th1 cells in vivo. Stem Cells. (2015) 33:1200–12. doi: 10.1002/stem.1934
Ma Y, Wang Z, Zhang A, Xu F, Zhao N, Xue J, et al. Human placenta-derived mesenchymal stem cells ameliorate GVHD by modulating Th17/Tr1 balance via expression of PD-L2. Life Sci. (2018) 214:98–105. doi: 10.1016/j.lfs.2018.10.061
Pires AO, Mendes-Pinheiro B, Teixeira FG, Anjo SI, Ribeiro-Samy S, Gomes ED, et al. Unveiling the differences of secretome of human bone marrow mesenchymal stem cells, adipose tissue-derived stem cells, and human umbilical cord perivascular cells: a proteomic analysis. Stem Cells Dev. (2016) 25:1073–83. doi: 10.1089/scd.2016.0048
Ito R, Katano I, Kawai K, Yagoto M, Takahashi T, Ka Y, et al. A novel xenogeneic graft- vs.-host disease model for investigating the pathological role of human CD4(+) or CD8(+) T cells using immunodeficient NOG mice. Am J Transpl. (2017) 17:1216–28. doi: 10.1111/ajt.14116
Li X, Bai J, Ji X, Li R, Xuan Y, Wang Y. Comprehensive characterization of four different populations of human mesenchymal stem cells as regards their immune properties, proliferation and differentiation. Int J Mol Med. (2014) 34:695–704. doi: 10.3892/ijmm.2014.1821
Fazzina R, Iudicone P, Fioravanti D, Bonanno G, Totta P, Zizzari IG, et al. Potency testing of mesenchymal stromal cell growth expanded in human platelet lysate from different human tissues.* Stem Cell Res Ther. (2016) 7:122. doi: 10.1186/s13287-016-0383-3
Prasanna SJ, Gopalakrishnan D, Shankar SR, Vasandan AB. Pro-inflammatory cytokines, IFNgamma and TNFalpha, influence immune properties of human bone marrow and Wharton jelly mesenchymal stem cells differentially. PloS ONE. (2010) 5:e9016. doi: 10.1371/journal.pone.0009016
Jitschin R, Mougiakakos D, von BL, Volkl S, Moll G, Ringden O, et al. Alterations in the cellular immune compartment of patients treated with third-party mesenchymal stromal cells following allogeneic hematopoietic stem-cell transplantation. Stem Cells. (2013) 31:1715–25. doi: 10.1002/stem.1386
Barcia RN, Santos JM, Filipe M, Teixeira M, Martins JP, Almeida J, et al. What makes umbilical cord tissue-derived mesenchymal stromal cells superior immunomodulators when compared to bone marrow derived mesenchymal stromal cells? Stem Cells Int. (2015) 2015:583984. doi: 10.1155/2015/583984
Chao YH, Wu HP, Wu KH, Tsai YG, Peng CT, Lin KC, et al. An increase in CD3+CD4+CD25+ regulatory T cells after administration of umbilical cord-derived mesenchymal stem cells during sepsis. PloS ONE. (2014) 9:e110338. doi: 10.1371/journal.pone.0110338
Patel SR, Copland IB, Garcia MA, Metz R, Galipeau J. Human mesenchymal stromal cells suppress T-cell proliferation independent of heme oxygenase-1. Cytotherapy. (2015) 17:382–91. doi: 10.1016/j.jcyt.2014.11.010
Karlsson H, Erkers T, Nava S, Ruhm S, Westgren M, Ringden O. Stromal cells from term fetal membrane are highly suppressive in allogeneic settings in vitro. Clin Exp Immunol. (2012) 167:543–55. doi: 10.1111/j.1365-2249.2011.04540.x
de Witte SFH, Merino AM, Franquesa M, Strini T, van Zoggel JAA, Korevaar SS, et al. Cytokine treatment optimises the immunotherapeutic effects of umbilical cord-derived MSC for* treatment of inflammatory liver disease. Stem Cell Res Ther. (2017) 8:140. doi: 10.1186/s13287-017-0590-6
Ribeiro A, Laranjeira P, Mendes S, Velada I, Leite C, Andrade P, et al. Mesenchymal stem cells from umbilical cord matrix, adipose tissue and bone marrow exhibit different capability to suppress peripheral blood B, natural killer and T cells. Stem Cell Res Ther. (2013) 4:125. doi: 10.1186/scrt336
Jung JW, Kwon M, Choi JC, Shin JW, Park IW, Choi BW, et al. Familial occurrence of pulmonary embolism after intravenous, adipose tissue-derived stem cell therapy. Yonsei Med J. (2013) 54:1293–6. doi: 10.3349/ymj.2013.54.5.1293
Gleeson BM, Martin K, Ali MT, Kumar AH, Pillai MG, Kumar SP, et al. Bone marrow-derived mesenchymal stem cells have innate procoagulant activity and cause microvascular obstruction following intracoronary delivery: amelioration by antithrombin therapy. Stem Cells. (2015) 33:2726–37. doi: 10.1002/stem.2050
Ringden O, Uzunel M, Sundberg B, Lonnies L, Nava S, Gustafsson J, et al. Tissue repair using allogeneic mesenchymal stem cells for hemorrhagic cystitis, pneumomediastinum and perforated colon. Leukemia. (2007) 21:2271–6. doi: 10.1038/sj.leu.2404833
Ringden O, Baygan A, Remberger M, Gustafsson B, Winiarski J, Khoein B, et al. Placenta-derived decidua stromal cells for treatment of severe acute graft- vs.-host disease. Stem Cells Transl Med. (2018) 7:325–31. doi: 10.1002/sctm.17-0167
Melief SM, Schrama E, Brugman MH, Tiemessen MM, Hoogduijn MJ, Fibbe WE, et al. Multipotent stromal cells induce human regulatory T cells through a novel pathway involving skewing of monocytes toward anti-inflammatory macrophages. Stem Cells. (2013) 31:1980–91. doi: 10.1002/stem.1432
Galleu A, Riffo-Vasquez Y, Trento C, Lomas C, Dolcetti L, Cheung TS, et al. Apoptosis in mesenchymal stromal cells induces in vivo recipient-mediated immunomodulation. Sci Transl Med. (2017) 9:eaam7828. doi: 10.1126/scitranslmed.aam7828
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- vs.-host disease after experimental allogeneic stem cell transplantation. Bone Marrow Transpl. (2007) 39:637–45. doi: 10.1038/sj.bmt.1705644
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