Human umbilical cord mesenchymal stem cells hUC-MSCs exert immunosuppressive activities through a PGE2-dependent mechanism.
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.
Chen
Ke
K
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.
Wang
Ding
D
Du
Wei Ting
WT
Han
Zhi-Bo
ZB
Ren
He
H
Chi
Ying
Y
Yang
Shao Guang
SG
Zhu
Delin
D
Bayard
Francis
F
Han
Zhong Chao
ZC
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
D016207:Cytokines; D012333:RNA, Messenger; D007371:Interferon-gamma; D051546:Cyclooxygenase 2; D015232:Dinoprostone