PMID- 37678974 OWN - NLM STAT- MEDLINE DCOM- 20230915 LR - 20230927 IS - 1878-0814 (Electronic) IS - 1877-1173 (Linking) VI - 199 DP - 2023 TI - Universal and hypoimmunogenic pluripotent stem cells for clinical usage. PG - 271-296 LID - S1877-1173(23)00059-5 [pii] LID - 10.1016/bs.pmbts.2023.02.014 [doi] AB - It is urgent to prepare and store large numbers of clinical trial grade human pluripotent stem (hPS) cells for off-the-shelf use in stem cell therapies. However, stem cell banks, which store off-the-shelf stem cells, need financial support and large amounts of technicians for daily cell maintenance. Therefore, it is valuable to create "universal" or "hypoimmunogenic" hPS cells with genome editing engineering by knocking in or out immune-related genes. Only a small number of universal or hypoimmunogenic hPS cell lines should be needed to store for off-the-shelf usage and reduce the large amounts of instruments, consumables and technicians. In this article, we consider how to create hypoimmunogenic or universal hPS cells as well as the demerits of the technology. beta2-Microglobulin-knockout hPS cells did not harbor human leukocyte antigen (HLA)-expressing class I cells but led to the activation of natural killer cells. To escape the activities of macrophages and natural killer cells, homozygous hPS cells having a single allele of an HLA class I gene, such as HLA-C, were proposed. Major HLA class Ia molecules were knocked out, and CD47, HLA-G and PD-L1 were knocked in hPS cells utilizing CRISPR/Cas9 genome editing. Finally, some researchers are trying to generate universal hPS cells without genome editing. The cells evaded the activation of not only T cells but also macrophages and natural killer cells. These universal hPS cells have high potential for application in cell therapy. CI - Copyright (c) 2023. Published by Elsevier Inc. FAU - Sung, Tzu-Cheng AU - Sung TC AD - State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China. FAU - Maitiruze, Kailibinuer AU - Maitiruze K AD - State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China. FAU - Pan, Jiandong AU - Pan J AD - State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China. FAU - Gong, Jian AU - Gong J AD - Department of Laboratory Medicine, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China. FAU - Bai, Yongheng AU - Bai Y AD - Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital, Wenzhou Medical University, The First Affiliated Hospital Area, Wenzhou, Zhejiang, P.R. China. FAU - Pan, Xiaodong AU - Pan X AD - Department of Urology, The First Affiliated Hospital, Wenzhou Medical University, The First Affiliated Hospital Area, Wenzhou, Zhejiang, P.R. China. FAU - Higuchi, Akon AU - Higuchi A AD - State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China; Department of Chemical and Materials Engineering, National Central University, Jhongli, Taoyuan, Taiwan. Electronic address: higuchi@wmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230316 PL - Netherlands TA - Prog Mol Biol Transl Sci JT - Progress in molecular biology and translational science JID - 101498165 RN - 0 (HLA Antigens) SB - IM MH - *Pluripotent Stem Cells/cytology/immunology/metabolism MH - HLA Antigens MH - Humans MH - *Stem Cell Transplantation MH - Gene Knockdown Techniques MH - Gene Knockout Techniques MH - Gene Editing MH - Gene Knock-In Techniques MH - Animals MH - Transplantation Immunology MH - Biological Specimen Banks OTO - NOTNLM OT - Cell therapy OT - Human leukocyte antigen OT - Hypoimmunogenic hPS cells OT - Immune privilege OT - Off-the-shelf cells OT - Universal hPS cells EDAT- 2023/09/08 00:41 MHDA- 2023/09/11 06:43 CRDT- 2023/09/07 20:57 PHST- 2023/09/11 06:43 [medline] PHST- 2023/09/08 00:41 [pubmed] PHST- 2023/09/07 20:57 [entrez] AID - S1877-1173(23)00059-5 [pii] AID - 10.1016/bs.pmbts.2023.02.014 [doi] PST - ppublish SO - Prog Mol Biol Transl Sci. 2023;199:271-296. doi: 10.1016/bs.pmbts.2023.02.014. Epub 2023 Mar 16.