title: Insensitivity of Human iPS Cells-Derived Mesenchymal Stem Cells to Interferon-γ-induced HLA Expression Potentiates Repair Efficiency of Hind Limb Ischemia in Immune Humanized NOD Scid Gamma Mice.
abstract: 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-γ (IFN-γ), 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-γ 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-γ-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.
authors.affiliation: Otorhinolaryngology Hospital, The First Affiliated Hospital, Guangzhou, Guangdong, People's Republic of China.|The Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Yue-Qi
authors.initials: YQ
authors.lastname: Sun
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.|Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Yuelin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Emergency, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Otorhinolaryngology Hospital, The First Affiliated Hospital, Guangzhou, Guangdong, People's Republic of China.|The Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Meng-Xia
authors.initials: MX
authors.lastname: Deng
authors.affiliation: Otorhinolaryngology Hospital, The First Affiliated Hospital, Guangzhou, Guangdong, People's Republic of China.|The Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Wen-Xiang
authors.initials: WX
authors.lastname: Gao
authors.affiliation: Otorhinolaryngology Hospital, The First Affiliated Hospital, Guangzhou, Guangdong, People's Republic of China.|The Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Sin-Ming
authors.initials: SM
authors.lastname: Chiu
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Camie W
authors.initials: CW
authors.lastname: Chan
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Hung-Fat
authors.initials: HF
authors.lastname: Tse
authors.affiliation: Otorhinolaryngology Hospital, The First Affiliated Hospital, Guangzhou, Guangdong, People's Republic of China.|The Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Shi
authors.affiliation: Otorhinolaryngology Hospital, The First Affiliated Hospital, Guangzhou, Guangdong, People's Republic of China.|The Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Qing-Ling
authors.initials: QL
authors.lastname: Fu
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.|Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.|Shenzhen Institutes of Research and Innovation, The University of Hong Kong, Shenzhen, Guangdong, People's Republic of China.
authors.forename: Qizhou
authors.initials: Q
authors.lastname: Lian
mesh_terms: D000818:Animals; D064593:Heterografts; D006614:Hindlimb / Q000098:blood supply*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology*; D007511:Ischemia / Q000378:metabolism / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID
chemical_list: D000949:Histocompatibility Antigens Class II; C573415:IFNG protein, human; D007371:Interferon-gamma
keywords: Human leukocyte antigen class II; Immune humanized mice; Induced pluripotent stem cells; Mesenchymal stem cells