Progress on stem cell research towards the treatment of Parkinson's disease.
Progress on stem cell research towards the treatment of Parkinson's disease.
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DOI：
10.1186/scrt102
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发表时间：
2012-04-03
影响因子：
7.5
通讯作者：
Shen S
中科院分区：
文献类型：
--
作者：
Gibson SA;Gao GD;McDonagh K;Shen S
帕金森病（PD）是一种神经退行性疾病，其特征是路易体包涵体的进行性积累，并伴有大脑黑质纹状体束中多巴胺能（DA）神经元的选择性破坏。遗传学研究揭示了PD的病理生理学，使诊断的生物标志物和治疗的遗传靶点的识别成为可能，这些都是随着干细胞技术的发展而发展的。诱导多能干细胞（iPS）的发现有助于从成人体细胞中提取干细胞进行个性化治疗，从而不仅克服了人类胚胎干细胞有限的可用性，而且还克服了围绕其使用的伦理问题。正在开发非病毒、非整合或非dna介导的重编程技术。生成中脑DA神经元的方案正在不断改进。iPS细胞衍生的DA神经元为研究体外疾病进展和筛选具有新治疗潜力的分子提供了细胞模型，并对改善帕金森动物的行为有有益的影响。更安全的非病毒/无偏见重编程策略的进一步发展和随后同质的中脑DA神经元的产生将为临床试验铺平道路。一种药物、细胞替代和基因治疗相结合的方法来阻止疾病的进展并改善治疗方法可能很快就会实现。
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive accumulation of Lewy body inclusions along with selective destruction of dopaminergic (DA) neurons in the nigrostriatal tract of the brain. Genetic studies have revealed much about the pathophysiology of PD, enabling the identification of both biomarkers for diagnosis and genetic targets for therapeutic treatment, which are evolved in tandem with the development of stem cell technologies. The discovery of induced pluripotent stem (iPS) cells facilitates the derivation of stem cells from adult somatic cells for personalized treatment and thus overcomes not only the limited availability of human embryonic stem cells but also ethical concerns surrounding their use. Non-viral, non-integration, or non-DNA-mediated reprogramming technologies are being developed. Protocols for generating midbrain DA neurons are undergoing constant refinement. The iPS cell-derived DA neurons provide cellular models for investigating disease progression in vitro and for screening molecules of novel therapeutic potential and have beneficial effects on improving the behavior of parkinsonian animals. Further progress in the development of safer non-viral/non-biased reprogramming strategies and the subsequent generation of homogenous midbrain DA neurons shall pave the way for clinical trials. A combined approach of drugs, cell replacement, and gene therapy to stop disease progression and to improve treatment may soon be within our reach.
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影响因子：
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