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Human mesenchymal stem cells derived from umbilical cord and bone marrow exert immunomodulatory effects in different mechanisms

查看全文 作　　者：Yunejin [1,2,3]Song;Jung-Yeon [1,2,4]Lim;Taekyu [5]Lim;Keon-Il [2]Im;Nayoun [2]Kim;Young-Sun [2,6]Nam;Young-Woo [2]Jeon;Jong Chul [7]Shin;Hyun Sun [8]Ko;In Yang [8]Park;Seok-Goo [2,6,9]Cho 高影响力作者 机构地区：[1]Institute for Translational Research and Molecular Imaging,College of Medicine,The Catholic University of Korea,Seoul 06591,South Korea;[2]Laboratory of Immune Regulation,Convergent Research Consortium for Immunologic Disease,College of Medicine,The Catholic University of Korea,Seoul 06591,South Korea;[3]Department of Biomedicine and Health Sciences,College of Medicine,The Catholic University of Korea,Seoul 06591,South Korea;[4]Precision Immunology Institute,Icahn School of Medicine at Mount Sinai,New York,NY 10029,United States;[5]Division of Hematology Oncology,Department of Internal Medicine,Veterans Health Service Medical Center,Seoul 05368,South Korea;[6]Department of Hematology,Catholic Blood and Marrow Transplantation Center,Seoul St.Mary’s Hospital,College of Medicine,The Catholic University of Korea,Seoul 06591,South Korea;[7]Department of Obstetrics and Gynecology,CHA Bundang Medical Center,CHA University,Seongnam 13496,South Korea;[8]Department of Obstetrics and Gynecology,College of Medicine,The Catholic University of Korea,Seoul 06591,South Korea;[9]Division of Hematology,Department of Internal Medicine,College of Medicine,The Catholic University of Korea,Seoul 06591,South Korea高影响力机构 出　　处：《World Journal of Stem Cells》索引2020年第12卷第9期,共18页高影响力期刊 基　　金：Supported by Korean Health Technology R&D Project,No.HI16C2178. 摘　　要：BACKGROUND Mesenchymal stem cells(MSCs)are an attractive tool to treat graft-versus-host disease because of their unique immunoregulatory properties.Although human bone marrow-derived MSCs(BM-MSCs)were the most widely used MSCs in cell therapy until recently,MSCs derived from human umbilical cords(UC-MSCs)have gained popularity as cell therapy material for their ethical and noninvasive collection.AIM To investigate the difference in mechanisms of the immunosuppressive effects of UC-MSCs and BM-MSCs.METHODS To analyze soluble factors expressed by MSCs,such as indolamine 2,3-dioxygenase,cyclooxygenase-2,prostaglandin E2 and interleukin(IL)-6,inflammatory environments in vitro were reconstituted with combinations of interferon-gamma(IFN-γ),tumor necrosis factor alpha and IL-1βor with IFN-γalone.Activated T cells were cocultured with MSCs treated with indomethacin and/or anti-IL-10.To assess the ability of MSCs to inhibit T helper 17 cells and induce regulatory T cells,induced T helper 17 cells were cocultured with MSCs treated with indomethacin or anti-IL-10.Xenogeneic graft-versus-host disease was induced in NOG mice(NOD/Shi-scid/IL-2Rγnull)and UC-MSCs or BM-MSCs were treated as cell therapies.RESULTS Our data demonstrated that BM-MSCs and UC-MSCs shared similar phenotypic characteristics and immunomodulation abilities.BM-MSCs expressed more indolamine 2,3-dioxygenase after cytokine stimulation with different combinations of IFN-γ,tumor necrosis factor alpha-αand IL-1βor IFN-γalone.UC-MSCs expressed more prostaglandin E2,IL-6,programmed death-ligand 1 and 2 in the in vitro inflammatory environment.Cyclooxygenase-2 and IL-10 were key factors in the immunomodulatory mechanisms of both MSCs.In addition,UC-MSCs inhibited more T helper 17 cells and induced more regulatory T cells than BM-MSCs.UC-MSCs and BM-MSCs exhibited similar effects on attenuating graft-versus-host disease.CONCLUSION UC-MSCs and BM-MSCs exert similar immunosuppressive effects with different mechanisms involved.These findings suggest that UC-MSCs have distinct immunoregulatory functions and may substitute BM-MBSCs in the field of cell therapy. 关 键 词：Mesenchymal stem cells Graft-versus-host disease Umbilical cord Cell therapy Xenogeneic mouse model IMMUNOMODULATION
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