Interferon-γpriming enhances the therapeutic effects of menstrual blood-derived stromal cells in a mouse liver ischemia-reperfusion model  

作　　者：Qi Zhang Si-Ning Zhou Jia-Min Fu Li-Jun Chen Yang-Xin Fang Zhen-Yu Xu Hui-Kang Xu Yin Yuan Yu-Qi Huang Ning Zhang Yi-Fei Li Charlie Xiang 

机构地区：[1]State Key Laboratory for Diagnosis and Treatment of Infectious Diseases,National Clinical Research Center for Infectious Diseases,National Medical Center for Infectious Diseases,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,Zhejiang Province,China [2]Research Units of Infectious Disease and Microecology,Chinese Academy of Medical Sciences,Hangzhou 310003,Zhejiang Province,China [3]Innovative Precision Medicine Group,Shulan Hospital,Hangzhou 311215,Zhejiang Province,China [4]The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,Zhejiang Province,China

出　　处：《World Journal of Stem Cells》2023年第9期876-896,共21页世界干细胞杂志（英文版）（电子版）

基　　金：National Key R&D Program of China,No.2022YFA1105603 and 2022YFC2304405;Hangzhou Science and Technology Project,China,No.20200224;National Natural Science Foundation of China,No.81900563;Key Research&Development Plan of Zhejiang Province,China,No.2019C03015 and 2020C04016。

摘　　要：BACKGROUND Mesenchymal stem cells(MSCs)have been used in liver transplantation and have certain effects in alleviating liver ischemia-reperfusion injury(IRI)and regulating immune rejection.However,some studies have indicated that the effects of MSCs are not very significant.Therefore,approaches that enable MSCs to exert significant and stable therapeutic effects are worth further study.AIM To enhance the therapeutic potential of human menstrual blood-derived stromal cells(MenSCs)in the mouse liver ischemia-reperfusion(I/R)model via interferon-γ(IFN-γ)priming.METHODS Apoptosis was analyzed by flow cytometry to evaluate the safety of IFN-γpriming,and indoleamine 2,3-dioxygenase(IDO)levels were measured by quantitative real-time reverse transcription polymerase chain reaction,western blotting,and ELISA to evaluate the efficacy of IFN-γpriming.In vivo,the liver I/R model was established in male C57/BL mice,hematoxylin and eosin and TUNEL staining was performed and serum liver enzyme levels were measured to assess the degree of liver injury,and regulatory T cell(Treg)numbers in spleens were determined by flow cytometry to assess immune tolerance potential.Metabolomics analysis was conducted to elucidate the potential mechanism underlying the regulatory effects of primed MenSCs.In vitro,we established a hypoxia/reoxygenation(H/R)model and analyzed apoptosis by flow cytometry to investigate the mechanism through which primed MenSCs inhibit apoptosis.Transmission electron microscopy,western blotting,and immunofluorescence were used to analyze autophagy levels.RESULTS IFN-γ-primed MenSCs secreted higher levels of IDO,attenuated liver injury,and increased Treg numbers in the mouse spleens to greater degrees than untreated MenSCs.Metabolomics and autophagy analyses proved that primed MenSCs more strongly induced autophagy in the mouse livers.In the H/R model,autophagy inhibitors increased the level of H/R-induced apoptosis,indicating that autophagy exerted protective effects.In addition,primed MenSCs decreased the leve

关 键 词：Mesenchymal stem cells Cell therapy Reperfusion injury T-LYMPHOCYTES AUTOPHAGY Liver 

分 类 号：R730.5[医药卫生—肿瘤]