Induced pluripotent stem cells and neurodegenerative diseases

Abstract

Neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease and Amyotrophic Lateral Sclerosis, are characterized by idiopathic neuron loss in different regions of the central nervous system, which contributes to the relevant dysfunctions in the patients. The application of cell replacement therapy using human embryonic stem (hES) cells, though having attracted much attention, has been hampered by the intrinsic ethical problems. It has been demonstrated that adult somatic cells can be reprogrammed into the embryonic state, called induced pluripotent stem (iPS) cells. It is soon realized that iPS cells may be an alternative source for cell replacement therapy, because it raises no ethical problems and using patient-specific iPS cells for autologous transplantation will not lead to immunological rejection. What’s more, certain types of neurons derived from patient-specific iPS cells may display disease-relevant phenotypes. Thus, patientspecific iPS cells can provide a unique opportunity to directly investigate the pathological properties of relevant neural cells in individual patient, and to study the vulnerability of neural cells to pathogenic factors in vitro, which may help reveal the pathogenesis of many neurodegenerative diseases. In this review, the recent development in cellular treatment of neurodegenerative diseases using iPS cells was summarized, and the potential value of iPS cells in the modeling of neurodegenerative disease was discussed.

摘要

神经退行性疾病, 包括帕金森病、 阿尔茨海默病和肌萎缩侧索硬化症等的共同特征是在中枢神经系统的不同部位发生特发性神经元丢失。 这些神经元的丢失给病人造成了一系列相应的功能障碍。 应用人类胚胎干细胞进行细胞替代治疗曾引起人们很大的兴趣, 但是一些伦理学问题阻碍了该研究的发展。 通过导入特定的转录因子, 体细胞能够被诱导为具有胚胎干细胞特性的细胞, 即诱导多能干细胞 (induced pluripotent stem cells, iPS cells)。 获取人类iPS细胞并不涉及明显的伦理问题, 并且运用病人特异性的iPS细胞能使自体移植成为可能。 因此, iPS细胞有可能成为细胞替代治疗中可靠的细胞来源。 此外, 利用iPS细胞, 人们还能在体外直接研究病变神经细胞的表型以及神经细胞在特定致病因子作用下的疾病易感性, 有助于揭示神经退行性疾病的内在机制。 本文综述了iPS细胞用于神经退行性疾病细胞治疗的最新进展, 并探讨了其在建立疾病的细胞模型中的潜在价值。