Dopaminergic neurons generated from monkey embryonic stem cells function in a Parkinson primate model
Dopaminergic neurons generated from monkey embryonic stem cells function in a Parkinson primate model
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DOI：
10.1172/jci200521137
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发表时间：
2005-01-01
影响因子：
15.9
通讯作者：
Hashimoto, N
中科院分区：
文献类型：
--
作者：
Takagi, Y;Takahashi, J;Hashimoto, N
帕金森病 (PD) 是一种神经退行性疾病，其特征是中脑多巴胺能 (DA) 神经元丧失。 ES细胞目前是PD细胞替代治疗最有前途的供体细胞来源。我们之前描述了基质细胞表面存在的强烈神经化活性，称为基质细胞衍生诱导活性（SDIA）。在这项研究中，我们生成了由来自猴 ES 细胞的神经祖细胞组成的神经球，这些神经祖细胞能够产生大量 DA 神经元。我们证明FGF20优先在黑质中表达，与FGF2协同作用以增加ES细胞衍生的神经球中DA神经元的数量。我们还分析了将猴 ES 细胞产生的 DA 神经元移植到经 1-甲基-4-苯基-1,2,3,6-四氢吡啶处理（MPTP 处理）的猴子（一种 PD 灵长类动物模型）中的效果。行为研究和功能成像表明，移植的细胞起到 DA 神经元的作用，并减轻 MPTP 诱导的神经系统症状。
Parkinson disease (PD) is a neurodegenerative disorder characterized by loss of midbrain dopaminergic (DA) neurons. ES cells are currently the most promising donor cell source for cell-replacement therapy in PD. We previously described a strong neuralizing activity present on the surface of stromal cells, named stromal cell-derived inducing activity (SDIA). In this study, we generated neurospheres composed of neural progenitors from monkey ES cells, which are capable of producing large numbers of DA neurons. We demonstrated that FGF20, preferentially expressed in the substantia nigra, acts synergistically with FGF2 to increase the number of DA neurons in ES cell-derived neurospheres. We also analyzed the effect of transplantation of DA neurons generated from monkey ES cells into 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated (MPTP-treated) monkeys, a primate model for PD. Behavioral studies and functional imaging revealed that the transplanted cells functioned as DA neurons and attenuated MPTP-induced neurological symptoms.