PMID- 34093711 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210608 IS - 1687-966X (Print) IS - 1687-9678 (Electronic) VI - 2021 DP - 2021 TI - HLA DR Genome Editing with TALENs in Human iPSCs Produced Immune-Tolerant Dendritic Cells. PG - 8873383 LID - 10.1155/2021/8873383 [doi] LID - 8873383 AB - Although human induced pluripotent stem cells (iPSCs) can serve as a universal cell source for regenerative medicine, the use of iPSCs in clinical applications is limited by prohibitive costs and prolonged generation time. Moreover, allogeneic iPSC transplantation requires preclusion of mismatches between the donor and recipient human leukocyte antigen (HLA). We, therefore, generated universally compatible immune nonresponsive human iPSCs by gene editing. Transcription activator-like effector nucleases (TALENs) were designed for selective elimination of HLA DR expression. The engineered nucleases completely disrupted the expression of HLA DR on human dermal fibroblast cells (HDF) that did not express HLA DR even after stimulation with IFN-gamma. Teratomas formed by HLA DR knockout iPSCs did not express HLA DR, and dendritic cells differentiated from HLA DR knockout iPSCs reduced CD4(+) T cell activation. These engineered iPSCs might provide a novel translational approach to treat multiple recipients from a limited number of cell donors. CI - Copyright (c) 2021 Yoo-Wook Kwon et al. FAU - Kwon, Yoo-Wook AU - Kwon YW AUID- ORCID: 0000-0003-2418-429X AD - Strategic Center of Cell and Bio Therapy for Heart, Diabetes & Cancer, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea. FAU - Ahn, Hyo-Suk AU - Ahn HS AD - Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea. FAU - Lee, Jin-Woo AU - Lee JW AD - Strategic Center of Cell and Bio Therapy for Heart, Diabetes & Cancer, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea. FAU - Yang, Han-Mo AU - Yang HM AD - Cardiovascular Center & Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Republic of Korea. FAU - Cho, Hyun-Jai AU - Cho HJ AD - Cardiovascular Center & Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Republic of Korea. FAU - Kim, Seok Joong AU - Kim SJ AD - ToolGen, Inc., #1204, Byucksan Digital Valley 6-cha, 219 Gasan Digital 1-ro, Geumcheon-gu, Seoul 08501, Republic of Korea. FAU - Lee, Shin-Hyae AU - Lee SH AD - SK Chemical, Life Science Business, Clinical Research Team, Gyeonggi-do, 13494, Republic of Korea. FAU - Yang, Heung-Mo AU - Yang HM AD - GenNBio, Inc., 422, Teheran-ro, Gangnam-gu, Seoul 06193, Republic of Korea. FAU - Jang, Hyun-Duk AU - Jang HD AD - Strategic Center of Cell and Bio Therapy for Heart, Diabetes & Cancer, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea. FAU - Kim, Sung Joo AU - Kim SJ AD - GenNBio, Inc., 422, Teheran-ro, Gangnam-gu, Seoul 06193, Republic of Korea. FAU - Kim, Hyo-Soo AU - Kim HS AUID- ORCID: 0000-0003-0847-5329 AD - Strategic Center of Cell and Bio Therapy for Heart, Diabetes & Cancer, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea. AD - Cardiovascular Center & Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Republic of Korea. AD - Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 03080, Republic of Korea. LA - eng PT - Journal Article DEP - 20210520 PL - United States TA - Stem Cells Int JT - Stem cells international JID - 101535822 PMC - PMC8163544 COIS- The authors declare no conflict of interest. EDAT- 2021/06/08 06:00 MHDA- 2021/06/08 06:01 PMCR- 2021/05/20 CRDT- 2021/06/07 05:51 PHST- 2020/08/26 00:00 [received] PHST- 2021/03/30 00:00 [revised] PHST- 2021/04/24 00:00 [accepted] PHST- 2021/06/07 05:51 [entrez] PHST- 2021/06/08 06:00 [pubmed] PHST- 2021/06/08 06:01 [medline] PHST- 2021/05/20 00:00 [pmc-release] AID - 10.1155/2021/8873383 [doi] PST - epublish SO - Stem Cells Int. 2021 May 20;2021:8873383. doi: 10.1155/2021/8873383. eCollection 2021.