Pre-clinical safety and efficacy of human induced pluripotent stem cell-derived products for autologous cell therapy in Parkinson's disease.

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Tác giả: Bob Carter, Young Cha, Todd M Herrington, Yean Ju Hong, Heejin Jang, Jeha Jeon, Kwang-Soo Kim, Minseon Kim, Seo-Hyun Kim, Sanghyeok Ko, Sek Won Kong, Pierre Leblanc, In-Hee Lee, Nayeon Lee, Serhiy Naumenko, HoeWon Park, Tae-Yoon Park, Hannah L Ryu, Jeffrey Schweitzer, Zenith Shrestha, Bin Song, Ki-Jun Yoon

Ngôn ngữ: eng

Ký hiệu phân loại: 296.123 Mishnah

Thông tin xuất bản: United States : Cell stem cell , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 96741

Human induced pluripotent stem cell (hiPSC)-derived midbrain dopaminergic cells (mDACs) represent a promising source for autologous cell therapy in Parkinson's disease (PD), but standardized regulatory criteria are essential for clinical translation. In this pre-clinical study, we generated multiple clinical-grade hiPSC lines from freshly biopsied fibroblasts of four sporadic PD patients using episomal reprogramming and differentiated them into mDACs using a refined 21-day protocol. Rigorous evaluations included whole-genome/exome sequencing, RNA sequencing, and in vivo studies, including a 39-week Good Laboratory Practice-compliant mouse safety study. While mDACs from all lines met safety criteria, mDACs from one patient failed to improve rodent behavioral outcomes, underscoring inter-individual variability. Importantly, in vitro assessments did not reliably predict in vivo efficacy, identifying dopaminergic fiber density as a key efficacy criterion. These findings support comprehensive quality control guidelines for autologous cell therapy and pave the way for a clinical trial with eight sporadic PD patients, scheduled to commence in 2025.
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