Transplantation of monkey ES cell-derived dopaminergic neurons into the brain of MPTP-treated monkey

帕金森病是一种神经退行性疾病，以中脑多巴胺(DA)能神经元缺失为特征。胚胎干细胞目前是帕金森氏病细胞替代疗法最有前途的供体细胞来源。我们先前描述了基质细胞表面存在的一种强烈的神经化活性，称为SDIA(基质细胞衍生诱导活性)。在本研究中，我们从猴ES细胞中生成了由神经前体细胞组成的神经球，这种神经球能够产生大量的DA神经元。我们证明，优先在黑质表达的FGF20与FGF2协同作用，增加了ES细胞来源的神经球中DA神经元的数量。我们还分析了将从猴ES细胞中产生的DA神经元移植到1-甲基-4-苯基-1，2，3，6-四氢吡啶(MPTP)治疗的猴子-帕金森病灵长类动物模型的效果。行为学研究和功能成像显示，移植的细胞具有DA神经元的功能，并减轻了MPTP诱导的神经症状。

Parkinson's disease 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 of Parkinson's disease. We previously described a strong neuralizing activity present on the surface of stromal cells, named SDIA (stromal cell-derived inducing activity). 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, acted 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 (MPTP)-treated monkeys, a primate model for Parkinson's disease. Behavioral studies and functional imaging revealed that the transplanted cells functioned as DA neurons and attenuated MPTP-induced neurological symptoms.