Autologous mesenchymal stem cell-derived dopaminergic neurons function in parkinsonian macaques
Autologous mesenchymal stem cell-derived dopaminergic neurons function in parkinsonian macaques
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DOI：
10.1172/jci62516
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发表时间：
2013-01-01
影响因子：
15.9
通讯作者：
Dezawa, Mari
中科院分区：
文献类型：
--
作者：
Hayashi, Takuya;Wakao, Shohei;Dezawa, Mari
基于细胞的多巴胺能神经元替代疗法一直是帕金森病研究的长期目标。在这里，我们表明，自体移植A9多巴胺能神经元样细胞诱导间充质干细胞（MSC）导致长期生存的细胞和恢复运动功能的帕金森病猕猴。分化的MSCs表达A9多巴胺能神经元的标记物，并在体外去极化后释放多巴胺。将分化的自体细胞移植到纹状体的受影响部分。接受移植的动物在运动行为方面表现出适度和逐步的改善。使用[C-11]-CFT（多巴胺转运蛋白（DAT）的配体）的正电子发射断层扫描（PET）显示DAT表达急剧增加，随后在7个月内呈指数下降。PET结果的动力学分析显示，DAT表达保持高于基线水平超过7个月。9个月时的免疫组织化学评价一致表明，移植纹状体中存在DAT和其他A9多巴胺能神经元标记物阳性的细胞。这些数据表明，分化的自体间充质干细胞移植可能是一种安全有效的细胞治疗帕金森病。
A cell-based therapy for the replacement of dopaminergic neurons has been a long-term goal in Parkinson's disease research. Here, we show that autologous engraftment of A9 dopaminergic neuron-like cells induced from mesenchymal stem cells (MSCs) leads to long-term survival of the cells and restoration of motor function in hemiparkinsonian macaques. Differentiated MSCs expressed markers of A9 dopaminergic neurons and released dopamine after depolarization in vitro. The differentiated autologous cells were engrafted in the affected portion of the striatum. Animals that received transplants showed modest and gradual improvements in motor behaviors. Positron emission tomography (PET) using [C-11]-CFT, a ligand for the dopamine transporter (DAT), revealed a dramatic increase in DAT expression, with a subsequent exponential decline over a period of 7 months. Kinetic analysis of the PET findings revealed that DAT expression remained above baseline levels for over 7 months. Immunohistochemical evaluations at 9 months consistently demonstrated the existence of cells positive for DAT and other A9 dopaminergic neuron markers in the engrafted striatum. These data suggest that transplantation of differentiated autologous MSCs may represent a safe and effective cell therapy for Parkinson's disease.