Autologous iPSC-derived dopamine neuron transplantation in a nonhuman primate Parkinson's disease model

被引:48
作者
Wang, Shuyan [1 ,2 ,3 ,4 ]
Zou, Chunlin [5 ]
Fu, Linlin [1 ,2 ]
Wang, Bin [1 ,2 ]
An, Jing [1 ,2 ]
Song, Gongru [1 ,2 ]
Wu, Jianyu [1 ,2 ]
Tang, Xihe [1 ,2 ]
Li, Mo [1 ,2 ]
Zhang, Jian [5 ]
Yue, Feng [6 ]
Zheng, Chengyun [7 ]
Chan, Piu [4 ,6 ]
Zhang, Y. Alex [1 ,2 ]
Chen, Zhiguo [1 ,2 ,3 ,4 ]
机构
[1] Capital Med Univ, Cell Therapy Ctr, Beijing Inst Geriatr, Xuanwu Hosp, Beijing, Peoples R China
[2] Minist Educ, Key Lab Neurodegenerat, Beijing, Peoples R China
[3] Beijing Inst Brain Disorders, Ctr Neural Injury & Repair, Beijing, Peoples R China
[4] Beijing Inst Brain Disorders, Ctr Parkinsons Dis, Beijing, Peoples R China
[5] Guangxi Med Univ, Ctr Translat Med, Nanning, Peoples R China
[6] Capital Med Univ, Beijing Inst Geriatr, Dept Neurobiol, Xuanwu Hosp, Beijing, Peoples R China
[7] Shandong Univ, Dept Hematol, Hosp 2, Jinan, Shandong, Peoples R China
基金
中国国家自然科学基金;
关键词
iPSC; dopamine neurons; autologous; transplantation; Parkinson's disease; cynomolgus monkey; PLURIPOTENT STEM-CELLS; SIMIAN FOAMY VIRUSES; DIRECT CONVERSION; MOUSE FIBROBLASTS; HUMAN ES; DIFFERENTIATION; INDUCTION; BRAIN; FOXA2; DEGENERATION;
D O I
10.1038/celldisc.2015.12
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Autologous dopamine (DA) neurons are a new cell source for replacement therapy of Parkinson's disease (PD). In this study, we tested the safety and efficacy of autologous induced pluripotent stem cell (iPSC)-derived DA cells for treatment of a cynomolgus monkey PD model. Monkey bone marrow mesenchymal cells were isolated and induced to iPSCs, followed by differentiation into DA cells using a method with high efficiency. Autologous DA cells were introduced into the brain of a cynomolgus monkey PD model without immunosuppression; three PD monkeys that had received no grafts served as controls. The PD monkey that had received autologous grafts experienced behavioral improvement compared with that of controls. Histological analysis revealed no overgrowth of grafts and a significant number of surviving A9 region-specific graft-derived DA neurons. The study provided a proof-of-principle to employ iPSC-derived autologous DA cells for PD treatment using a nonhuman primate PD model.
引用
收藏
页数:11
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