PMID- 35747945 OWN - NLM STAT- MEDLINE DCOM- 20221004 LR - 20221213 IS - 2211-5463 (Electronic) IS - 2211-5463 (Linking) VI - 12 IP - 10 DP - 2022 Oct TI - Generation of universal natural killer cells from a cryopreserved cord blood mononuclear cell-derived induced pluripotent stem cell library. PG - 1771-1781 LID - 10.1002/2211-5463.13460 [doi] AB - Natural killer (NK) cells play a key role in innate immunity and are regarded as a promising candidate for cellular immunotherapy. Natural killer cells may be generated from different sources, including induced pluripotent stem cells (iPSCs); these stem cells produce an abundant amount of NK cells to meet the needs of a wide range of clinical applications. Autologous iPSCs are expensive and labor-intensive to prepare, while allogeneic iPSCs require human leukocyte antigen (HLA) matched cells to avoid the risk of immune rejection. In the current study, we prepared HLA-matched iPSCs using HLA common haplotype homozygous (HLAh) donors from cryopreserved human cord blood (CB) sourced from the Tianjin Cord Blood Public Bank. This approach was designed to generate a CB-derived iPSC library from HLAh donors and use it to produce off-the-shelf NK cells. Starting with readily available cryopreserved CB mononuclear cells (cryoCBMCs), we produced cryoCBMC-derived iPSCs (cryoCB-iPSCs). These cryoCB-iPSCs were induced to generate embryoid bodies (EBs) using an improved 3D suspension culture method, and induced NK (iNK) cells were differentiated from EBs. iNK cells expressed specific surface markers of NK cells, exhibited cytotoxicity comparable with NK cells generated from CB (CB-NK) and peripheral blood (PB-NK), and expressed lower levels of KIRs and HLA-DR compared to CB-NK and PB-NK. Taken together, we have shown that an iPSC library can be established from HLAh cryoCBMCs, and cryoCB-iPSCs can be used to generate a large number of 'universal' NK cells for future clinical applications. CI - (c) 2022 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. FAU - Du, Wei AU - Du W AUID- ORCID: 0000-0001-8705-1983 AD - Union Stem Cell & Gene Engineering Co., LTD, Tianjin, China. AD - School of Medicine, Nankai University, Tianjin, China. AD - Tianjin Key Laboratory of Blood Cell Therapy Technology, China. AD - National Stem Cell Product Industrialization Base, State Industrial Base for Stem Cell Engineering Products, Tianjin, China. FAU - Cui, Lijuan AU - Cui L AD - Union Stem Cell & Gene Engineering Co., LTD, Tianjin, China. AD - Tianjin Key Laboratory of Blood Cell Therapy Technology, China. AD - National Stem Cell Product Industrialization Base, State Industrial Base for Stem Cell Engineering Products, Tianjin, China. FAU - Zhang, Jinmei AU - Zhang J AD - Union Stem Cell & Gene Engineering Co., LTD, Tianjin, China. AD - Tianjin Key Laboratory of Blood Cell Therapy Technology, China. AD - National Stem Cell Product Industrialization Base, State Industrial Base for Stem Cell Engineering Products, Tianjin, China. FAU - Zhang, Hua AU - Zhang H AD - Union Stem Cell & Gene Engineering Co., LTD, Tianjin, China. AD - Tianjin Key Laboratory of Blood Cell Therapy Technology, China. AD - National Stem Cell Product Industrialization Base, State Industrial Base for Stem Cell Engineering Products, Tianjin, China. FAU - Liu, Rongzhi AU - Liu R AD - Union Stem Cell & Gene Engineering Co., LTD, Tianjin, China. AD - Tianjin Key Laboratory of Blood Cell Therapy Technology, China. AD - National Stem Cell Product Industrialization Base, State Industrial Base for Stem Cell Engineering Products, Tianjin, China. FAU - Yang, Wenling AU - Yang W AD - Union Stem Cell & Gene Engineering Co., LTD, Tianjin, China. AD - National Stem Cell Product Industrialization Base, State Industrial Base for Stem Cell Engineering Products, Tianjin, China. FAU - Zhang, Yu AU - Zhang Y AD - Union Stem Cell & Gene Engineering Co., LTD, Tianjin, China. AD - Tianjin Key Laboratory of Blood Cell Therapy Technology, China. AD - National Stem Cell Product Industrialization Base, State Industrial Base for Stem Cell Engineering Products, Tianjin, China. AD - Vcanbio Cell & Gene Engineering Co., Ltd, Tianjin, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220701 PL - England TA - FEBS Open Bio JT - FEBS open bio JID - 101580716 RN - 0 (HLA Antigens) RN - 0 (Inducible T-Cell Co-Stimulator Protein) SB - IM MH - Fetal Blood/metabolism MH - HLA Antigens MH - Humans MH - *Induced Pluripotent Stem Cells/metabolism MH - Inducible T-Cell Co-Stimulator Protein/metabolism MH - Killer Cells, Natural PMC - PMC9527588 OTO - NOTNLM OT - cell therapy OT - cryopreserved cord blood mononuclear cells OT - induced pluripotent stem cells OT - natural killer cells COIS- The authors declare no conflict of interest. EDAT- 2022/06/25 06:00 MHDA- 2022/10/05 06:00 PMCR- 2022/07/01 CRDT- 2022/06/24 02:43 PHST- 2022/04/08 00:00 [revised] PHST- 2021/12/17 00:00 [received] PHST- 2022/06/22 00:00 [accepted] PHST- 2022/06/25 06:00 [pubmed] PHST- 2022/10/05 06:00 [medline] PHST- 2022/06/24 02:43 [entrez] PHST- 2022/07/01 00:00 [pmc-release] AID - FEB413460 [pii] AID - 10.1002/2211-5463.13460 [doi] PST - ppublish SO - FEBS Open Bio. 2022 Oct;12(10):1771-1781. doi: 10.1002/2211-5463.13460. Epub 2022 Jul 1.