PMID- 26175298 OWN - NLM STAT- MEDLINE DCOM- 20161027 LR - 20181202 IS - 1549-4918 (Electronic) IS - 1066-5099 (Linking) VI - 33 IP - 12 DP - 2015 Dec TI - Insensitivity of Human iPS Cells-Derived Mesenchymal Stem Cells to Interferon-gamma-induced HLA Expression Potentiates Repair Efficiency of Hind Limb Ischemia in Immune Humanized NOD Scid Gamma Mice. PG - 3452-67 LID - 10.1002/stem.2094 [doi] AB - Adult mesenchymal stem cells (MSCs) are immunoprivileged cells due to the low expression of major histocompatibility complex (MHC) II molecules. However, the expression of MHC molecules in human-induced pluripotent stem cells (iPSCs)-derived MSCs has not been investigated. Here, we examined the expression of human leukocyte antigen (HLA) in human MSCs derived from iPSCs, fetuses, and adult bone marrow (BM) after stimulation with interferon-gamma (IFN-gamma), compared their repair efficacy, cell retention, inflammation, and HLA II expression in immune humanized NOD Scid gamma (NSG) mice of hind limb ischemia. In the absence of IFN-gamma stimulation, HLA-II was expressed only in BM-MSCs after 7 days. Two and seven days after stimulation, high levels of HLA-II were observed in BM-MSCs, intermediate levels were found in fetal-MSCs, and very low levels in iPSC-MSCs. The levels of p-STAT1, interferon regulatory factor 1, and class II transactivator exhibited similar phenomena. Moreover, p-STAT1 antagonist significantly reversed the high expression of HLA-II in BM-MSCs. Compared to adult BM-MSCs, transplanting iPSC-MSCs into hu-PBMNC NSG mice revealed markedly more survival iPSC-MSCs, less inflammatory cell accumulations, and better recovery of hind limb ischemia. The expression of HLA-II in MSCs in the ischemia limbs was detected in BM-MSCs group but not in iPSC-MSCs group at 7 and 21 days after transplantation. Our results demonstrate that, compared to adult MSCs, human iPSC-MSCs are insensitive to proinflammatory IFN-gamma-induced HLA-II expression and iPSC-MSCs have a stronger immune privilege after transplantation. It may attribute to a better therapeutic efficacy in allogeneic transplantation. CI - (c) 2015 The Authors. STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press. FAU - Sun, Yue-Qi AU - Sun YQ AD - Otorhinolaryngology Hospital, The First Affiliated Hospital, Guangzhou, Guangdong, People's Republic of China. AD - The Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China. FAU - Zhang, Yuelin AU - Zhang Y AD - Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China. AD - Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China. FAU - Li, Xin AU - Li X AD - Department of Emergency, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, People's Republic of China. FAU - Deng, Meng-Xia AU - Deng MX AD - Otorhinolaryngology Hospital, The First Affiliated Hospital, Guangzhou, Guangdong, People's Republic of China. AD - The Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China. FAU - Gao, Wen-Xiang AU - Gao WX AD - Otorhinolaryngology Hospital, The First Affiliated Hospital, Guangzhou, Guangdong, People's Republic of China. AD - The Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China. FAU - Yao, Yin AU - Yao Y AD - Otorhinolaryngology Hospital, The First Affiliated Hospital, Guangzhou, Guangdong, People's Republic of China. AD - The Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China. FAU - Chiu, Sin-Ming AU - Chiu SM AD - Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China. FAU - Liang, Xiaoting AU - Liang X AD - Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China. FAU - Gao, Fei AU - Gao F AD - Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China. FAU - Chan, Camie W AU - Chan CW AD - Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China. FAU - Tse, Hung-Fat AU - Tse HF AD - Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China. FAU - Shi, Jianbo AU - Shi J AD - Otorhinolaryngology Hospital, The First Affiliated Hospital, Guangzhou, Guangdong, People's Republic of China. AD - The Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China. FAU - Fu, Qing-Ling AU - Fu QL AD - Otorhinolaryngology Hospital, The First Affiliated Hospital, Guangzhou, Guangdong, People's Republic of China. AD - The Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China. FAU - Lian, Qizhou AU - Lian Q AD - Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China. AD - Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China. AD - Shenzhen Institutes of Research and Innovation, The University of Hong Kong, Shenzhen, Guangdong, People's Republic of China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150806 PL - England TA - Stem Cells JT - Stem cells (Dayton, Ohio) JID - 9304532 RN - 0 (Histocompatibility Antigens Class II) RN - 0 (IFNG protein, human) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - Heterografts MH - Hindlimb/*blood supply MH - Histocompatibility Antigens Class II/*biosynthesis MH - Humans MH - Induced Pluripotent Stem Cells/*metabolism MH - Interferon-gamma/*pharmacology MH - Ischemia/metabolism/*therapy MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/*metabolism MH - Mice MH - Mice, Inbred NOD MH - Mice, SCID OTO - NOTNLM OT - Human leukocyte antigen class II OT - Immune humanized mice OT - Induced pluripotent stem cells OT - Mesenchymal stem cells EDAT- 2015/07/16 06:00 MHDA- 2016/11/01 06:00 CRDT- 2015/07/16 06:00 PHST- 2015/01/29 00:00 [received] PHST- 2015/06/06 00:00 [accepted] PHST- 2015/07/16 06:00 [entrez] PHST- 2015/07/16 06:00 [pubmed] PHST- 2016/11/01 06:00 [medline] AID - 10.1002/stem.2094 [doi] PST - ppublish SO - Stem Cells. 2015 Dec;33(12):3452-67. doi: 10.1002/stem.2094. Epub 2015 Aug 6.