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帕金森病(Parkinson’s disease,PD)是一种常见于中老年人的神经系统退行性疾病,由中脑腹侧的多巴胺能(dopaminergic,DA)神经元缺失造成。这类疾病可通过移植由人胚胎干细胞(human embryonic stem cells,h ESC)或其他途径获得的多巴胺能神经元实现治疗。然而,在应用于临床之前,需要对这些多巴胺能神经元的安全性和有效性在合适的动物模型中进行充分、全面的评价。为评价由临床级人胚胎干细胞分化的多巴胺能神经元是否安全、有效,根据先导专项部署,我们建立了MPTP诱导的帕金森病猴模型,并将由人胚胎干细胞定向分化的多巴胺能神经元植入受损猴脑区。结果表明,在所有接受细胞移植的猴中,未发生移植细胞形成的肿瘤和继发肿瘤。移植细胞可分化为多巴胺能神经元并使局部多巴胺水平提高,带来不同程度的行为学改善。这些发现提示,多能干细胞分化的多巴胺能神经元移植治疗帕金森病安全、有效,可进一步应用于帕金森病的治疗。
Parkinson’s disease (PD) is a neurodegenerative disease that is common in the elderly and is caused by a loss of dopaminergic (DA) neurons in the ventral midbrain. Such diseases can be treated by transplantation of dopaminergic neurons obtained from human embryonic stem cells (h ESC) or other pathways. However, the safety and efficacy of these dopaminergic neurons need to be fully and comprehensively assessed in appropriate animal models before they can be used clinically. To evaluate the safety and efficacy of dopaminergic neurons differentiated from clinical grade human embryonic stem cells, we established an MPTP-induced model of Parkinson’s disease in monkey based on pilot-specific deployment and implant dopaminergic neurons that are differentiated by human embryonic stem cells Impaired monkey brain area. The results show that in all monkeys that underwent cell transplantation, there was no transplanted cell-forming tumors and secondary tumors. Transplanted cells can differentiate into dopaminergic neurons and local dopamine levels, resulting in varying degrees of behavioral improvement. These findings suggest that pluripotent stem cell-differentiated dopaminergic neuron transplantation for the treatment of Parkinson’s disease is safe and effective and can be further applied to the treatment of Parkinson’s disease.