Engineering of human mesenchymal stem cells resistant to multiple natural killer subtypes

doi:10.7150/ijbs.64640

	Engineering of human mesenchymal stem cells resistant to multiple natural killer subtypes
	Zheng, Dejin 1,2,3; Wang, Xiaoyan 1,2,3; Zhang, Zhenwu1,2,3,4 ; Li, Enqin 1,2,3; Yeung, Cheungkwan 1,2,3; Borkar, Roma 1,2,3; Qin, Guihui 1,2,3; Wu, Yaojiong 5; Xu, Ren-He 1,2,3
	2022
发表期刊	INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
ISSN	1449-2288
卷号	18 期号:1
发表状态	已发表
DOI	10.7150/ijbs.64640
摘要	Mesenchymal stem cells (MSCs) as a therapeutic promise are often quickly cleared by innate immune cells of the host including natural killer (NK) cells. Efforts have been made to generate immune-escaping human embryonic stem cells (hESCs) where T cell immunity is evaded by defecting beta-2-microglobulin (B2M), a common unit for human leukocyte antigen (HLA) class I, and NK cells are inhibited via ectopic expression of HLA-E or -G. However, NK subtypes vary among recipients and even at different pathologic statuses. It is necessary to dissect and optimize the efficacy of the immune-escaping cells against NK subtypes. Here, we first generated B2M knockout hESCs and differentiated them to MSCs (EMSCs) and found that NK resistance occurred with B2M-/- EMSCs expressing HLA-E and -G only when they were transduced via an inducible lentiviral system in a dose-dependent manner but not when they were inserted into a safe harbor. HLA-E and -G expressed at high levels together in transduced EMSCs inhibited three major NK subtypes, including NKG2A+/LILRB1+, NKG2A+/LILRB1-, and NKG2A-/LILRB1+, which was further potentiated by IFN-gamma priming. Thus, this study engineers MSCs with resistance to multiple NK subtypes and underscores that dosage matters when a transgene is used to confer a novel effect to host cells, especially for therapeutic cells to evade immune rejection.
关键词	Human embryonic stem cells mesenchymal stem cells natural killer cells innate immunity immune rejection
URL	查看原文
收录类别	SCI ; SCIE
语种	英语
资助项目	University of Macau Research Committee funds MYRG["2016-00070-FHS","2017-00124-FHS"] ; Macau Science and Technology Development Fund (FDCT)["095/2017/A1","0112-2018-A3"] ; FDCT-National Natural Science Foundation of China[0008-2019-AFJ]
WOS研究方向	Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics
WOS类目	Biochemistry & Molecular Biology ; Biology
WOS记录号	WOS:000741493200004
出版者	IVYSPRING INT PUBL
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/150323
专题	生命科学与技术学院_PI研究组_林照博组
通讯作者	Xu, Ren-He
作者单位	1.Univ Macau, Fac Hlth Sci, Ctr Reprod Dev & Aging, Taipa, Macau, Peoples R China 2.Univ Macau, Fac Hlth Sci, Inst Translat Med, Taipa, Macau, Peoples R China 3.Univ Macau, Minist Educ, Frontiers Sci Ctr Precis Oncol, Taipa, Macau, Peoples R China 4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 5.Tsinghua Univ, Int Grad Sch Shenzhen, Shenzhen Key Lab Hlth Sci & Technol, Shenzhen, Peoples R China
推荐引用方式 GB/T 7714	Zheng, Dejin,Wang, Xiaoyan,Zhang, Zhenwu,et al. Engineering of human mesenchymal stem cells resistant to multiple natural killer subtypes[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,2022,18(1).
APA	Zheng, Dejin.,Wang, Xiaoyan.,Zhang, Zhenwu.,Li, Enqin.,Yeung, Cheungkwan.,...&Xu, Ren-He.(2022).Engineering of human mesenchymal stem cells resistant to multiple natural killer subtypes.INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,18(1).
MLA	Zheng, Dejin,et al."Engineering of human mesenchymal stem cells resistant to multiple natural killer subtypes".INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES 18.1(2022).