Chan Wook Park, Sanghyun Park, Seok Jong Chung, Phil Hyu Lee, Dong-Wook Kim
{"title":"Dissecting divergent outcomes in stem cell-derived dopamine cell therapy trials for Parkinson's disease.","authors":"Chan Wook Park, Sanghyun Park, Seok Jong Chung, Phil Hyu Lee, Dong-Wook Kim","doi":"10.1016/j.stem.2026.07.002","DOIUrl":null,"url":null,"abstract":"<p><p>Fetal tissue transplantation established proof-of-concept for dopamine cell replacement in Parkinson's disease but yielded inconsistent outcomes due to limited tissue availability and cellular heterogeneity. Advances in generating high-purity dopamine progenitors from pluripotent stem cells have enabled standardized products that show safety and motor improvement in clinical trials. However, these trials revealed divergent outcomes arising at three levels: between clinical studies, driven by differences in cell products, baseline patient characteristics, or immunosuppressants; between patients, influenced by alloimmune factors, genetic background, or co-pathology; and within patients, where graft survival varies across transplantation sites due to the local microenvironment or surgical technique.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"1257-1269"},"PeriodicalIF":20.4000,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell stem cell","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.stem.2026.07.002","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/7/24 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Fetal tissue transplantation established proof-of-concept for dopamine cell replacement in Parkinson's disease but yielded inconsistent outcomes due to limited tissue availability and cellular heterogeneity. Advances in generating high-purity dopamine progenitors from pluripotent stem cells have enabled standardized products that show safety and motor improvement in clinical trials. However, these trials revealed divergent outcomes arising at three levels: between clinical studies, driven by differences in cell products, baseline patient characteristics, or immunosuppressants; between patients, influenced by alloimmune factors, genetic background, or co-pathology; and within patients, where graft survival varies across transplantation sites due to the local microenvironment or surgical technique.