biostudies-literatureHirayama MMinistry of Health, Labour and WelfareJapan Agency for Medical Research and DevelopmentMinistry of Education, Culture, Sports, Science and TechnologyMinistry of Economy, Trade and Industry101847https://www.ebi.ac.uk/biostudies/studies/S-EPMC11866429biostudies-literatureUnknown6(1)A first-in-human investigator-initiated clinical study of a corneal endothelial cell substitute (CLS001) derived from a clinical-grade induced pluripotent stem cell (iPSC) line shows improvement of visual acuity and corneal stromal edema, with no adverse events for up to 1 year after surgery for the treatment of bullous keratopathy. While preclinical tests, including multiple whole-genome analysis and tumorigenicity tests adhering to the Food and Drug Administration (FDA) draft guidelines, are negative, an additional whole-genome analysis conducted on transplanted CLS001 cells reveals a de novo in-frame deletion of exon22 in the EP300 gene. No adverse events related to the mutation are observed. Our study demonstrates the feasibility of using iPSC-derived cells to replace donor transplant Cell reports. MedicineA first-in-human clinical study of an allogenic iPSC-derived corneal endothelial cell substitute transplantation for bullous keratopathy.PMC11866429JP21bk0104123Aso KDohi HNegishi KOkano HShimmura SHatou SSayano THokama RHirayama OINomura MTakasu NInagaki EHanatani THirayama MfalseA first-in-human clinical study of an allogenic iPSC-derived corneal endothelial cell substitute transplantation for bullous keratopathy.A first-in-human investigator-initiated clinical study of a corneal endothelial cell substitute (CLS001) derived from a clinical-grade induced pluripotent stem cell (iPSC) line shows improvement of visual acuity and corneal stromal edema, with no adverse events for up to 1 year after surgery for the treatment of bullous keratopathy. While preclinical tests, including multiple whole-genome analysis and tumorigenicity tests adhering to the Food and Drug Administration (FDA) draft guidelines, are negative, an additional whole-genome analysis conducted on transplanted CLS001 cells reveals a de novo in-frame deletion of exon22 in the EP300 gene. No adverse events related to the mutation are observed. Our study demonstrates the feasibility of using iPSC-derived cells to replace donor transplant 2025-01-01T00:00:00Z2025 Jan2026-06-02T08:09:36.039Z2025-04-04T02:12:34.345ZS-EPMC118664293980926210.1016/j.xcrm.2024.101847