title: Characterization of HLA-G and Related Immunosuppressive Effects in Human Umbilical Cord Stroma-Derived Stem Cells.
abstract: Mesenchymal stem cells (MSCs) and especially those derived from fetal tissues exert a potent immunosuppressive effect that can be enhanced under inflammatory conditions. This study aimed to explore the immunosuppressive properties of human umbilical cord mesenchymal stem cells (HUCMSCs). We found that HLA-G, the nonclassical HLA allele with strong immune-inhibitory properties, was much more expressed on the HUCMSCs than on MSCs of other origins. Flow cytometry revealed that 90.8% of the HUCMSCs expressed HLA-G. RT-PCR revealed expression of HLA-G1, HLA-G5, and HLA-G7 in all of four HUCMSC lines. In a mixed lymphocyte reaction assay, the HUCMSCs inhibited the proliferation of lymphocytes by 35 ± 3% and could be reversed by treatment with an HLA-G blocking antibody. Upon coculture with the HUCMSCs, peripheral blood mononuclear cells expressed lower levels of proinflammatory mediators such as IL-6, TNF-α, and VEGF-α. This immunosuppressive effect was enhanced when the HUCMSCs were pretreated with IFN-γ, such that the expression of HLA-G was highly activated and HLA-DR diminished. The same phenomenon was not observed in MSCs derived from bone marrow or the placenta. In a xenograft rejection assay, the HUCMSCs survived in immunocompetent mice, whereas primary fibroblasts did not survive. This study confirms the HLA-G-related immunosuppressive property of HUCMSCs, which is more potent than MSCs of other origin. A good tolerance of this mesenchymal stem cell in allogeneic transplantation can thus be anticipated.
authors.affiliation: Department of Obstetrics and Gynecology, Buddhist Tzu-Chi Buddhist General Hospital, Hualien, Taiwan.
authors.forename: Dah-Ching
authors.initials: DC
authors.lastname: Ding
authors.forename: Hsiang-Lan
authors.initials: HL
authors.lastname: Chou
authors.forename: Yu-Hsun
authors.initials: YH
authors.lastname: Chang
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Hung
authors.forename: Hwan-Wun
authors.initials: HW
authors.lastname: Liu
authors.forename: Tang-Yuan
authors.initials: TY
authors.lastname: Chu
mesh_terms: D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D059951:HLA-G Antigens / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed / Q000379:methods; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology*; D011247:Pregnancy; D014470:Umbilical Cord / Q000166:cytology*
chemical_list: D059951:HLA-G Antigens