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/jci21137
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发表时间：
2005-01
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影响因子：
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通讯作者：
Y. Takagi;J. Takahashi;H. Saiki;A. Morizane;Takuya Hayashi;Y. Kishi;Hitoshi Fukuda;Yo Okamoto;M. Koyanagi;M. Ideguchi;H. Hayashi;Takayuki Imazato;H. Kawasaki;H. Suemori;S. Omachi;H. Iida;N. Itoh;N. Nakatsuji;Y. Sasai;N. Hashimoto
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文献类型：
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作者：
Y. Takagi;J. Takahashi;H. Saiki;A. Morizane;Takuya Hayashi;Y. Kishi;Hitoshi Fukuda;Yo Okamoto;M. Koyanagi;M. Ideguchi;H. Hayashi;Takayuki Imazato;H. Kawasaki;H. Suemori;S. Omachi;H. Iida;N. Itoh;N. Nakatsuji;Y. Sasai;N. Hashimoto
帕金森病（PD）是一种以中脑多巴胺能（DA）神经元丧失为特征的神经退行性疾病。胚胎干细胞是目前PD细胞替代治疗中最有希望的供体细胞来源。我们之前描述了一种存在于基质细胞表面的强神经化活性，称为基质细胞衍生诱导活性（SDIA）。在这项研究中，我们从猴胚胎干细胞中生成了由神经祖细胞组成的神经球，这种细胞能够产生大量的DA神经元。我们证明优先表达于黑质的FGF20与FGF2协同作用，增加ES细胞衍生的神经球中DA神经元的数量。我们还分析了将猴胚胎干细胞生成的DA神经元移植到1-甲基-4-苯基-1,2,3,6-四氢吡啶处理（mptp处理）的猴（PD灵长类动物模型）的效果。行为学研究和功能成像显示，移植细胞具有DA神经元功能，并减轻了mptp诱导的神经症状。
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.