title: Human umbilical cord mesenchymal stem cells hUC-MSCs exert immunosuppressive activities through a PGE2-dependent mechanism.
abstract: Human umbilical-cord-derived mesenchymal stem cells (hUC-MSCs) constitute an attractive alternative to bone-marrow-derived MSCs for potential clinical applications because of easy preparation and lower risk of viral contamination. In this study, both proliferation of human peripheral blood mononuclear cells (hPBMCs) and their IFN-gamma production in response to mitogenic or allogeneic stimulus were effectively inhibited by hUC-MSCs. Co-culture experiments in transwell systems indicated that the suppression was largely mediated by soluble factor(s). Blocking experiments identified prostaglandin E(2) (PGE(2)) as the major factor, because inhibition of PGE(2) synthesis almost completely mitigated the immunosuppressive effects, whereas neutralization of TGF-beta, IDO, and NO activities had little effects. Moreover, the inflammatory cytokines, IFN-gamma and IL-1beta, produced by hPBMCs upon activation notably upregulated the expression of cyclooxygenase-2 (COX-2) and the production of PGE(2) by hUC-MSCs. In conclusion, our data have demonstrated for the first time the PGE(2)-mediated mechanism by which hUC-MSCs exert their immunomodulatory effects.
authors.affiliation: The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, Tianjin 300020, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Chen
authors.forename: Ding
authors.initials: D
authors.lastname: Wang
authors.forename: Wei Ting
authors.initials: WT
authors.lastname: Du
authors.forename: Zhi-Bo
authors.initials: ZB
authors.lastname: Han
authors.forename: He
authors.initials: H
authors.lastname: Ren
authors.forename: Ying
authors.initials: Y
authors.lastname: Chi
authors.forename: Shao Guang
authors.initials: SG
authors.lastname: Yang
authors.forename: Delin
authors.initials: D
authors.lastname: Zhu
authors.forename: Francis
authors.initials: F
authors.lastname: Bayard
authors.forename: Zhong Chao
authors.initials: ZC
authors.lastname: Han
mesh_terms: D049109:Cell Proliferation; D002469:Cell Separation; D018920:Coculture Techniques; D051546:Cyclooxygenase 2 / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D015232:Dinoprostone / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D014470:Umbilical Cord / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D007371:Interferon-gamma; D051546:Cyclooxygenase 2; D015232:Dinoprostone