Kang Ji-Feng, Tang Bei-Sha, Guo Ji-Feng
Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; State Key Laboratory of Medical Genetics, Changsha, Hunan 410008, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan 410008, China; Neurodegenerative Disorders Research Center, Central South University, Changsha, Hunan 410008, China.
Stem Cells Int. 2016;2016:4126214. doi: 10.1155/2016/4126214. Epub 2016 Jan 6.
In recent years, induced pluripotent stem cells (iPSCs) were widely used for investigating the mechanisms of Parkinson's disease (PD). Somatic cells from patients with SNCA (α-synuclein), LRRK2 (leucine-rich repeat kinase 2), PINK1 (PTEN induced putative kinase 1), Parkin mutations, and at-risk individuals carrying GBA (β-glucocerebrosidase) mutations have been successfully induced to iPSCs and subsequently differentiated into dopaminergic (DA) neurons. Importantly, some PD-related cell phenotypes, including α-synuclein aggregation, mitophagy, damaged mitochondrial DNA, and mitochondrial dysfunction, have been described in these iPSCs models, which further investigated the pathogenesis of PD. In 2007, Takahashi et al. and Vodyanik et al. generated iPSCs from human somatic cells for the first time. Since then, patients derived iPSCs were applied for disease modeling, drug discovery and screening, autologous cell replacement therapy, and other biological applications. iPSC research has now become a hot topic in a wide range of fields. This review summarizes the recent progress of PD patients derived iPSC models in pathogenic mechanism investigation and potential clinical applications, especially their promising strategy in pharmacological study and DA neurons transplantation therapy. However, the challenges of iPSC transplantation still exist, and it has a long way to go before it can be used in clinical application.
近年来，诱导多能干细胞（iPSC）被广泛用于研究帕金森病（PD）的发病机制。来自携带SNCA（α-突触核蛋白）、LRRK2（富含亮氨酸重复激酶2）、PINK1（PTEN诱导的假定激酶1）、Parkin基因突变的患者以及携带GBA（β-葡萄糖脑苷脂酶）突变的高危个体的体细胞已成功诱导为iPSC，随后分化为多巴胺能（DA）神经元。重要的是，在这些iPSC模型中已经描述了一些与PD相关的细胞表型，包括α-突触核蛋白聚集、线粒体自噬、线粒体DNA损伤和线粒体功能障碍，这进一步深入研究了PD的发病机制。2007年，高桥等人和沃迪亚尼克等人首次从人类体细胞中生成了iPSC。从那时起，患者来源的iPSC被应用于疾病建模、药物发现与筛选、自体细胞替代治疗以及其他生物学应用。iPSC研究现已成为众多领域的热门话题。本综述总结了PD患者来源的iPSC模型在致病机制研究和潜在临床应用方面的最新进展，特别是它们在药理学研究和DA神经元移植治疗方面的前景策略。然而，iPSC移植的挑战仍然存在，在其可用于临床应用之前仍有很长的路要走。
