PMID- 33174655 OWN - NLM STAT- MEDLINE DCOM- 20201210 LR - 20201214 IS - 1365-2184 (Electronic) IS - 0960-7722 (Print) IS - 0960-7722 (Linking) VI - 53 IP - 12 DP - 2020 Dec TI - Generation of universal and hypoimmunogenic human pluripotent stem cells. PG - e12946 LID - 10.1111/cpr.12946 [doi] LID - e12946 AB - There is a need to store very large numbers of conventional human pluripotent stem cell (hPSC) lines for their off-the-shelf usage in stem cell therapy. Therefore, it is valuable to generate "universal" or "hypoimmunogenic" hPSCs with gene-editing technology by knocking out or in immune-related genes. A few universal or hypoimmunogenic hPSC lines should be enough to store for their off-the-shelf usage. Here, we overview and discuss how to prepare universal or hypoimmunogenic hPSCs and their disadvantages. beta2-Microglobulin-knockout hPSCs did not harbour human leukocyte antigen (HLA)-expressing class I cells but rather activated natural killer (NK) cells. To avoid NK cell and macrophage activities, homozygous hPSCs expressing a single allele of an HLA class I molecule, such as HLA-C, were developed. Major HLA class I molecules were knocked out, and PD-L1, HLA-G and CD47 were knocked in hPSCs using CRISPR/Cas9 gene editing. These cells escaped activation of not only T cells but also NK cells and macrophages, generating universal hPSCs. CI - (c) 2020 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd. FAU - Ye, Qingsong AU - Ye Q AUID- ORCID: 0000-0002-2868-9247 AD - School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China. AD - Center of Regenerative Medicine, Renmin Hospital of Wuhan University, Wuhan, China. AD - Skeletal Biology Research Center, Department of Oral Maxillofacial Surgery, Massachusetts General Hospital & Harvard School of Dental Medicine, Boston, MA, USA. FAU - Sung, Tzu-Cheng AU - Sung TC AUID- ORCID: 0000-0003-4052-8048 AD - School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, China. AD - Department of Chemical and Materials Engineering, National Central University, Taoyuan, Taiwan. FAU - Yang, Jen-Ming AU - Yang JM AD - Department of Chemical and Materials Engineering, Chang Gung University, Taoyuan, Taiwan. FAU - Ling, Qing-Dong AU - Ling QD AUID- ORCID: 0000-0002-6432-6179 AD - Cathay Medical Research Institute, Cathay General Hospital, Taipei, Taiwan. FAU - He, Yan AU - He Y AUID- ORCID: 0000-0002-0949-8525 AD - School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China. FAU - Higuchi, Akon AU - Higuchi A AUID- ORCID: 0000-0003-2970-8531 AD - School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, China. AD - Department of Chemical and Materials Engineering, National Central University, Taoyuan, Taiwan. AD - Wenzhou Institute, University of Chinese Academy of Science, Wenzhou, China. AD - Department of Chemical Engineering and R&D Center for Membrane Technology, Chung Yuan Christian University, Taoyuan, Taiwan. AD - Center for Emergent Matter Science, Riken, Saitama, Japan. LA - eng GR - 108-2221-E-008-037/Ministry of Science and Technology, Taiwan/ GR - 108-2221-E-008-057/Ministry of Science and Technology, Taiwan/ GR - 81701032/National Natural Science Foundation of China/ GR - 81871503/National Natural Science Foundation of China/ GR - 18K05251/Japan Society for the Promotion of Science/ PT - Journal Article PT - Review DEP - 20201111 PL - England TA - Cell Prolif JT - Cell proliferation JID - 9105195 SB - IM MH - CRISPR-Cas Systems/*genetics MH - Family Characteristics MH - *Gene Editing MH - Humans MH - Killer Cells, Natural/*cytology MH - Pluripotent Stem Cells/*cytology MH - Stem Cell Transplantation/methods PMC - PMC7705897 OTO - NOTNLM OT - regenerative medicine OT - stem cells COIS- The authors declare no conflicts of interest. EDAT- 2020/11/12 06:00 MHDA- 2020/12/15 06:00 PMCR- 2020/11/11 CRDT- 2020/11/11 08:39 PHST- 2020/10/04 00:00 [received] PHST- 2020/10/13 00:00 [accepted] PHST- 2020/11/12 06:00 [pubmed] PHST- 2020/12/15 06:00 [medline] PHST- 2020/11/11 08:39 [entrez] PHST- 2020/11/11 00:00 [pmc-release] AID - CPR12946 [pii] AID - 10.1111/cpr.12946 [doi] PST - ppublish SO - Cell Prolif. 2020 Dec;53(12):e12946. doi: 10.1111/cpr.12946. Epub 2020 Nov 11.