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CD47 and PD-L1 overexpression in proliferating human hepatocytes attenuated immune responses and ameliorated acute liver injury in mice

文献类型：期刊论文

作者Ma, Chen8,9; Cao, Huiying8,9; Sun, Zhen1,6,7; Deng, Qiangqiang8,9; Liu, Wenjing5,9; Xin, Yingying8,9; Qiao, Shida8,9; Cen, Jin1,7; Shu, Yajing1,7; Qi, Kai4
刊名AMERICAN JOURNAL OF TRANSPLANTATION
出版日期2023-12-01
卷号23期号:12页码:1832-1844
ISSN号1600-6135
关键词hepatocyte transplantation macrophages T cells survival function
DOI10.1016/j.ajt.2023.07.020
通讯作者Zhang, Ludi(zhangludi@sibcb.ac.cn) ; Pan, Guoyu(gypan@simm.ac.cn)
英文摘要Hepatocyte transplantation has the potential to treat acute liver failure and correct liver-based metabolic disorders. Proliferating human hepatocytes (ProliHHs) provide a large-scale source as an alternative to primary human hepatocytes. However, host rejection led to inefficient graft survival and function, which hindered the clinical application of cell therapy. Herein, we employed the lentiviral system to overexpress immunomodulatory factors programmed death-ligand 1 (cluster of differentiation 274) (CD274) and cluster of differentiation 47 (CD47) in ProliHHs. CD47+274 overexpression inhibited macrophage and T cell responses in vitro. After transplantation into mice via the spleen without immu-nosuppression, CD47+274 ProliHHs accumulation in the liver significantly increased for 48 hours compared with ProliHHs. Consistent with the in vitro results, CD47+274 ProliHHs were less aggregated and infiltrated by macrophages and also recruited fewer T cells in the liver. Seven days after transplantation, the human albumin level of engineered ProliHHs doubled compared with control group. CD47+274 ProliHHs further ameliorated the liver injury induced using concanavalin A. Overall, our results suggested CD47+274 over expression reduced innate and adaptive immune responses during hepatocyte transplantation, and the survival rate and graft function of transplanted hepatocyte-like cells were all significantly improved.
WOS关键词CELL THERAPY ; TRANSPLANTATION ; REJECTION
资助项目Chinese Academy of Sciences[XDA16020205] ; National Science Foundation of China[82173878] ; Youth Innovation Promotion Association CAS, China ; Independent Deployment Program of the Institute of Pharmaceutical Innovation of the Chinese Academy of Sciences[LX211004]
WOS研究方向Surgery ; Transplantation
语种英语
出版者ELSEVIER SCIENCE INC
WOS记录号WOS:001150166300001
源URL[http://119.78.100.183/handle/2S10ELR8/308912]  
专题中国科学院上海药物研究所
通讯作者Zhang, Ludi; Pan, Guoyu
作者单位1.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, CAS Ctr Excellence Mol Cell Sci, State Key Lab Cell Biol, Shanghai, Peoples R China
2.Univ Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol, State Key Lab Cell Biol,Chinese Acad Sci, Shanghai 200031, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
4.Shanghai Hexaell Biotech Co Ltd, Shanghai, Peoples R China
5.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Peoples R China
6.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
7.Univ Chinese Acad Sci, Beijing, Peoples R China
8.Univ Chinese Acad Sci, Beijing, Peoples R China
9.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Ma, Chen,Cao, Huiying,Sun, Zhen,et al. CD47 and PD-L1 overexpression in proliferating human hepatocytes attenuated immune responses and ameliorated acute liver injury in mice[J]. AMERICAN JOURNAL OF TRANSPLANTATION,2023,23(12):1832-1844.
APA Ma, Chen.,Cao, Huiying.,Sun, Zhen.,Deng, Qiangqiang.,Liu, Wenjing.,...&Pan, Guoyu.(2023).CD47 and PD-L1 overexpression in proliferating human hepatocytes attenuated immune responses and ameliorated acute liver injury in mice.AMERICAN JOURNAL OF TRANSPLANTATION,23(12),1832-1844.
MLA Ma, Chen,et al."CD47 and PD-L1 overexpression in proliferating human hepatocytes attenuated immune responses and ameliorated acute liver injury in mice".AMERICAN JOURNAL OF TRANSPLANTATION 23.12(2023):1832-1844.

入库方式： OAI收割

来源：上海药物研究所

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