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| Engineering of human mesenchymal stem cells resistant to multiple natural killer subtypes | |
| 2022 | |
| Source Publication | INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
 |
| ISSN | 1449-2288 |
| Volume | 18Issue:1 |
| Status | 已发表 |
| DOI | 10.7150/ijbs.64640 |
| Abstract | 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. |
| Keyword | Human embryonic stem cells mesenchymal stem cells natural killer cells innate immunity immune rejection |
| URL | 查看原文 |
| Indexed By | SCI ; SCIE |
| Language | 英语 |
| Funding Project | 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 Research Area | Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics |
| WOS Subject | Biochemistry & Molecular Biology ; Biology |
| WOS ID | WOS:000741493200004 |
| Publisher | IVYSPRING INT PUBL |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/150323 |
| Collection | 生命科学与技术学院_PI研究组_林照博组 |
| Corresponding Author | Xu, Ren-He |
| Affiliation | 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 |
| Recommended Citation 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). |
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