{"doi":"10.1016/j.stem.2025.08.012","title":"Safety and tolerability of RPESC-RPE transplantation in patients with dry age-related macular degeneration: Low-dose clinical outcomes","abstract":"Retinal pigment epithelium (RPE) cell atrophy in dry age-related macular degeneration (AMD) compromises photoreceptor cell function, leading to vision loss. Stem cell-based RPE replacement therapy aims to reverse disease progression and restore vision. RPESC-RPE-4W, a post-mitotic adult RPE stem cell-derived RPE (RPESC-RPE) progenitor cell product, exhibits consistent safety and efficacy in preclinical studies. The first-in-human clinical trial of RPESC-RPE-4W completed low-dose cohort 1 interventions (NCT04627428). Six subjects received a subretinal suspension of 50,000 RPESC-RPE-4W cells. No significant inflammation, tumor, or product-related serious adverse events were observed. Best-corrected visual acuity in the three worse-seeing group A subjects improved by an average of +21.67 letters from baseline at 12 months. Three better-seeing group B subjects improved by an average of +3.0 letters at 6 months. The positive safety and tolerability outcomes for low-dose cohort 1 enabled dose escalation to mid-dose RPESC-RPE-4W therapy for dry AMD. • Adult RPE stem cells generated RPE progenitor cells at 4 weeks of differentiation • Progenitor-stage RPE cells were implanted to treat dry AMD • Clinical outcomes from low-dose cohort 1 met primary safety endpoints • Visual acuity improvements were greater in worse-seeing subjects Retinal pigment epithelium (RPE) cell loss in dry age-related macular degeneration leads to progressive vision decline. Stern and others implanted adult RPE stem cell-derived RPE progeny at a 4-week progenitor stage of differentiation (RPESC-RPE-4W). First-in-human cohort 1 met primary safety endpoints, with greater visual improvement observed in worse-seeing eyes.","journal":"Cell stem cell","year":2025,"id":514043,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9496,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":555490,"name":"Brigitte L. Arduini","orcid":"0000-0002-8587-3518","position":1,"is_corresponding":false},{"id":883046,"name":"Susan L. Borden","orcid":null,"position":2,"is_corresponding":false},{"id":254057,"name":"Dhruv Sareen","orcid":"0000-0002-0898-9656","position":3,"is_corresponding":false},{"id":232373,"name":"Clive N. Svendsen","orcid":"0000-0001-8696-3446","position":4,"is_corresponding":false},{"id":405499,"name":"Paul P. Lee","orcid":"0000-0002-3338-136X","position":5,"is_corresponding":false},{"id":753324,"name":"Charles J. Ryan","orcid":"0000-0002-2081-3557","position":6,"is_corresponding":false},{"id":856245,"name":"Shilpa Kodati","orcid":"0000-0002-9690-5319","position":7,"is_corresponding":false},{"id":1376591,"name":"Caroline Nyaiburi","orcid":null,"position":8,"is_corresponding":false},{"id":1376592,"name":"Keith Wolsieffer","orcid":null,"position":9,"is_corresponding":false},{"id":1375958,"name":"Eun Jung Oh","orcid":"0000-0001-6268-109X","position":10,"is_corresponding":false},{"id":1376593,"name":"Shuna Park","orcid":null,"position":11,"is_corresponding":false},{"id":1376594,"name":"Glenna Ford","orcid":null,"position":12,"is_corresponding":false},{"id":1376595,"name":"Keith E. Dionne","orcid":null,"position":13,"is_corresponding":false},{"id":40564,"name":"Sally Temple","orcid":"0000-0001-7301-783X","position":14,"is_corresponding":false},{"id":788721,"name":"Jeffrey H. Stern","orcid":"0000-0002-5272-5025","position":15,"is_corresponding":false},{"id":354064,"name":"Rajesh C. Rao","orcid":"0000-0002-5776-8366","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T02:48:23.284782Z","pmid":"40961946","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}