Dissecting divergent outcomes in stem cell-derived dopamine cell therapy trials for Parkinson's disease.

IF 20.4
Cell stem cell Pub Date : 2026-08-06 Epub Date: 2026-07-24 DOI:10.1016/j.stem.2026.07.002
Chan Wook Park, Sanghyun Park, Seok Jong Chung, Phil Hyu Lee, Dong-Wook Kim
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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.

干细胞来源的多巴胺细胞治疗帕金森病试验的不同结果
胎儿组织移植为帕金森病的多巴胺细胞替代提供了概念证明,但由于组织可用性有限和细胞异质性,结果不一致。从多能干细胞中产生高纯度多巴胺祖细胞的进展使标准化产品在临床试验中显示出安全性和运动改善。然而,这些试验揭示了在三个层面上产生的不同结果:临床研究之间,由细胞产物、基线患者特征或免疫抑制剂的差异驱动;患者之间,受同种免疫因素、遗传背景或共同病理的影响;在患者体内,由于局部微环境或手术技术的不同,移植部位的移植存活率也不同。
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