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

doi:10.1016/j.ajt.2023.07.020

	CD47 and PD-L1 overexpression in proliferating human hepatocytes attenuated immune responses and ameliorated acute liver injury in mice
	Ma, Chen 1,2; Cao, Huiying 1,2; Sun, Zhen3,4,5 ; Deng, Qiangqiang 1,2; Liu, Wenjing 1,6; Xin, Yingying 1,2; Qiao, Shida 1,2; Cen, Jin 3,4; Shu, Yajing 3,4; Qi, Kai 7; Han, Li 1,2; Zhang, Ludi 3,4,9; Pan, Guoyu 1,2,8
	2023-12-01
发表期刊	AMERICAN JOURNAL OF TRANSPLANTATION (IF:8.9[JCR-2023],6.7[5-Year])
ISSN	1600-6135
EISSN	1600-6143
卷号	23 期号:12
发表状态	已发表
DOI	10.1016/j.ajt.2023.07.020
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.
关键词	hepatocyte transplantation macrophages T cells survival function
URL	查看原文
收录类别	SCI
语种	英语
资助项目	Chinese Academy of Sciences[XDA16020205] ; National Science Foundation of China[82173878] ; Independent Deployment Program of the Institute of Pharmaceutical Innovation of the Chinese Academy of Sciences[LX211004]
WOS研究方向	Surgery ; Transplantation
WOS类目	Surgery ; Transplantation
WOS记录号	WOS:001150166300001
出版者	ELSEVIER SCIENCE INC
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/349871
专题	生命科学与技术学院生命科学与技术学院_博士生
通讯作者	Zhang, Ludi; Pan, Guoyu
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China 2.Univ Chinese Acad Sci, Beijing, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, CAS Ctr Excellence Mol Cell Sci, State Key Lab Cell Biol, Shanghai, Peoples R China 4.Univ Chinese Acad Sci, Beijing, Peoples R China 5.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 6.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Peoples R China 7.Shanghai Hexaell Biotech Co Ltd, Shanghai, Peoples R China 8.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 9.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
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).
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).
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).