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

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World Journal of Stem Cells 2020年第9期12卷 1032-1049页

作者： Yunejin Song Jung-Yeon lim taekyu lim Keon-Il Im Nayoun Kim Young-Sun Nam Young-Woo Jeon Jong Chul Shin Hyun Sun Ko In Yang Park Seok-Goo Cho Institute for Translational Research and Molecular Imaging College of MedicineThe Catholic University of KoreaSeoul 06591South Korea Laboratory of Immune Regulation Convergent Research Consortium for Immunologic DiseaseCollege of MedicineThe Catholic University of KoreaSeoul 06591South Korea Department of Biomedicine and Health Sciences College of MedicineThe Catholic University of KoreaSeoul 06591South Korea Precision Immunology Institute Icahn School of Medicine at Mount SinaiNew YorkNY 10029United States Division of Hematology Oncology Department of Internal MedicineVeterans Health Service Medical CenterSeoul 05368South Korea Department of Hematology Catholic Blood and Marrow Transplantation CenterSeoul St.Mary’s HospitalCollege of MedicineThe Catholic University of KoreaSeoul 06591South Korea Department of Obstetrics and Gynecology CHA Bundang Medical CenterCHA UniversitySeongnam 13496South Korea Department of Obstetrics and Gynecology College of MedicineThe Catholic University of KoreaSeoul 06591South Korea Division of Hematology Department of Internal MedicineCollege of MedicineThe Catholic University of KoreaSeoul 06591South Korea

BACKGROUND Mesenchymal stem cells(MSCs)are an attractive tool to treat graft-versus-host disease because of their unique immunoregulatory *** 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 *** To investigate the difference in mechanisms of the immunosuppressive effects of UC-MSCs and *** 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-γ*** T cells were cocultured with MSCs treated with indomethacin and/or *** 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 *** graft-versus-host disease was induced in NOG mice(NOD/Shi-scid/IL-2Rγnull)and UC-MSCs or BM-MSCs were treated as cell *** Our data demonstrated that BM-MSCs and UC-MSCs shared similar phenotypic characteristics and immunomodulation ***-MSCs expressed more indolamine 2,3-dioxygenase after cytokine stimulation with different combinations of IFN-γ,tumor necrosis factor alpha-αand IL-1βor IFN-γ***-MSCs expressed more prostaglandin E2,IL-6,programmed death-ligand 1 and 2 in the in vitro inflammatory ***-2 and IL-10 were key factors in the immunomodulatory mechanisms of both *** addition,UC-MSCs inhibited more T helper 17 cells and induced more regulatory T cells than ***-MSCs and BM-MSCs exhibited similar effects on attenuating graft-versus-host *** UC-MSCs and BM-MSCs exert similar immunosuppressive effects with different mechanisms

关键词： Mesenchymal stem cells Graft-versus-host disease Umbilical cord Cell therapy Xenogeneic mouse model Immunomodulation

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