PMID- 26044082 OWN - NLM STAT- MEDLINE DCOM- 20161213 LR - 20220331 IS - 1555-3892 (Electronic) IS - 0963-6897 (Linking) VI - 25 IP - 2 DP - 2016 TI - Characterization of HLA-G and Related Immunosuppressive Effects in Human Umbilical Cord Stroma-Derived Stem Cells. PG - 217-28 LID - 10.3727/096368915X688182 [doi] AB - 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-alpha, and VEGF-alpha. This immunosuppressive effect was enhanced when the HUCMSCs were pretreated with IFN-gamma, 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. FAU - Ding, Dah-Ching AU - Ding DC AD - Department of Obstetrics and Gynecology, Buddhist Tzu-Chi Buddhist General Hospital, Hualien, Taiwan. FAU - Chou, Hsiang-Lan AU - Chou HL FAU - Chang, Yu-Hsun AU - Chang YH FAU - Hung, Wei-Ting AU - Hung WT FAU - Liu, Hwan-Wun AU - Liu HW FAU - Chu, Tang-Yuan AU - Chu TY LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150603 PL - United States TA - Cell Transplant JT - Cell transplantation JID - 9208854 RN - 0 (HLA-G Antigens) SB - IM MH - Cell Differentiation/physiology MH - Cell Proliferation/*physiology MH - Cells, Cultured MH - Coculture Techniques MH - Female MH - HLA-G Antigens/*immunology MH - Humans MH - Immune Tolerance/immunology MH - Leukocytes, Mononuclear/immunology MH - Lymphocyte Culture Test, Mixed/methods MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/*cytology/*immunology MH - Pregnancy MH - Umbilical Cord/*cytology EDAT- 2015/06/06 06:00 MHDA- 2016/12/15 06:00 CRDT- 2015/06/06 06:00 PHST- 2015/06/06 06:00 [entrez] PHST- 2015/06/06 06:00 [pubmed] PHST- 2016/12/15 06:00 [medline] AID - content-CT-1292_Ding_et_al [pii] AID - 10.3727/096368915X688182 [doi] PST - ppublish SO - Cell Transplant. 2016;25(2):217-28. doi: 10.3727/096368915X688182. Epub 2015 Jun 3.