PMID- 32712868 OWN - NLM STAT- MEDLINE DCOM- 20210602 LR - 20210602 IS - 2629-3277 (Electronic) IS - 2629-3277 (Linking) VI - 16 IP - 4 DP - 2020 Aug TI - Human Leukocyte Antigen Class I Pseudo-Homozygous Mesenchymal Stem Cells Derived from Human Induced Pluripotent Stem Cells. PG - 792-808 LID - 10.1007/s12015-020-09990-9 [doi] AB - Mesenchymal stem cells (MSC) are an important type of cell that are highly recognized for their safety and efficacy as a cell therapy agent. In order to obtain MSC, primary tissues (adipose tissue, bone marrow, and umbilical cord blood) must be used; however, these tissues, especially umbilical cord blood, are difficult to obtain due to various reasons, such as the low birth rate trend. In addition, to maximize the safety and efficacy of MSC as allogenic cell therapeutic agents, it is desirable to minimize the possibility of an immune rejection reaction after in vivo transplantation. This study tried to establish a novel method for producing induced pluripotent stem cells (iPSC)-derived MSC in which the human leukocyte antigen (HLA)-class I gene is knocked out. To do so, dermal fibroblast originated iPSC generation using Yamanaka 4-factor, HLA class I gene edited iPSC generation using CRISPR/Cas9, and differentiation from iPSC to MSC using MSC culture medium was utilized. Through this, HLA-A, B, and C pseudo-homozygous iPSC-derived MSC (KO iMSC) were produced by monoallelically knocking out the polymorphic HLA-A, B, and C genes, which are the major causes of immune rejection during allogenic cell transplantation. Produced KO iMSC possesses multipotency and it was safe in vivo to be able to be differentiated to cartilage. In addition, it was not attacked by natural killer cells unlike HLA class I null cells. In conclusion, KO iMSC that do not induce immune rejection during allogenic cell transplantation can be produced. In the future, KO iMSC can be successfully utilized as allogenic cell therapeutic agents for many recipients through HLA screening. FAU - Kwon, Daekee AU - Kwon D AD - Stem Cells and Regenerative Bioengineering Institute in Kangstem Biotech, Biomedical Science Building, #81 Seoul National University, Seoul, 08826, South Korea. FAU - Ahn, Hee-Jin AU - Ahn HJ AD - Stem Cells and Regenerative Bioengineering Institute in Kangstem Biotech, Biomedical Science Building, #81 Seoul National University, Seoul, 08826, South Korea. FAU - Han, Mi-Jung AU - Han MJ AD - Stem Cells and Regenerative Bioengineering Institute in Kangstem Biotech, Biomedical Science Building, #81 Seoul National University, Seoul, 08826, South Korea. FAU - Ji, Minjun AU - Ji M AD - Stem Cells and Regenerative Bioengineering Institute in Kangstem Biotech, Biomedical Science Building, #81 Seoul National University, Seoul, 08826, South Korea. FAU - Ahn, Jongchan AU - Ahn J AD - Stem Cells and Regenerative Bioengineering Institute in Kangstem Biotech, Biomedical Science Building, #81 Seoul National University, Seoul, 08826, South Korea. FAU - Seo, Kwang-Won AU - Seo KW AD - Stem Cells and Regenerative Bioengineering Institute in Kangstem Biotech, Biomedical Science Building, #81 Seoul National University, Seoul, 08826, South Korea. FAU - Kang, Kyung-Sun AU - Kang KS AUID- ORCID: 0000-0002-9322-741X AD - Stem Cells and Regenerative Bioengineering Institute in Kangstem Biotech, Biomedical Science Building, #81 Seoul National University, Seoul, 08826, South Korea. kangpub@snu.ac.kr. AD - Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul, 08826, South Korea. kangpub@snu.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Stem Cell Rev Rep JT - Stem cell reviews and reports JID - 101752767 RN - 0 (Histocompatibility Antigens Class I) SB - IM MH - Animals MH - Base Sequence MH - Cell Differentiation MH - Histocompatibility Antigens Class I/*metabolism MH - Homozygote MH - Humans MH - Induced Pluripotent Stem Cells/*cytology MH - Mesenchymal Stem Cells/*cytology MH - Mice, Inbred BALB C MH - Mice, Knockout MH - Mice, Nude MH - Models, Biological MH - Reproducibility of Results OTO - NOTNLM OT - Gene knockout OT - Human leukocyte antigen OT - Induced pluripotent stem cells OT - Mesenchymal stem cells EDAT- 2020/07/28 06:00 MHDA- 2021/06/03 06:00 CRDT- 2020/07/27 06:00 PHST- 2020/07/28 06:00 [pubmed] PHST- 2021/06/03 06:00 [medline] PHST- 2020/07/27 06:00 [entrez] AID - 10.1007/s12015-020-09990-9 [pii] AID - 10.1007/s12015-020-09990-9 [doi] PST - ppublish SO - Stem Cell Rev Rep. 2020 Aug;16(4):792-808. doi: 10.1007/s12015-020-09990-9.