Department of Physiology, Keio University School of Medicine, Tokyo, Japan; Next Generation Systems CFU, Eisai Co. Ltd., Ibaraki, Japan.
J Neurochem. 2014 May;129(3):388-99. doi: 10.1111/jnc.12625. Epub 2013 Dec 15.
Human induced pluripotent stem (iPS) cells obtained by reprogramming technology are a source of great hope, not only in terms of applications in regenerative medicine, such as cell transplantation therapy, but also for modeling human diseases and new drug development. In particular, the production of iPS cells from the somatic cells of patients with intractable diseases and their subsequent differentiation into cells at affected sites (e.g., neurons, cardiomyocytes, hepatocytes, and myocytes) has permitted the in vitro construction of disease models that contain patient-specific genetic information. For example, disease-specific iPS cells have been established from patients with neuropsychiatric disorders, including schizophrenia and autism, as well as from those with neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. A multi-omics analysis of neural cells originating from patient-derived iPS cells may thus enable investigators to elucidate the pathogenic mechanisms of neurological diseases that have heretofore been unknown. In addition, large-scale screening of chemical libraries with disease-specific iPS cells is currently underway and is expected to lead to new drug discovery. Accordingly, this review outlines the progress made via the use of patient-derived iPS cells toward the modeling of neurological disorders, the testing of existing drugs, and the discovery of new drugs. The production of human induced pluripotent stem (iPS) cells from the patients' somatic cells and their subsequent differentiation into specific cells have permitted the in vitro construction of disease models that contain patient-specific genetic information. Furthermore, innovations of gene-editing technologies on iPS cells are enabling new approaches for illuminating the pathogenic mechanisms of human diseases. In this review article, we outlined the current status of neurological diseases-specific iPS cell research and described recently obtained knowledge in the form of actual examples.
人类诱导多能干细胞（iPS 细胞）通过重编程技术获得，是一种极具希望的来源，不仅在再生医学中的细胞移植治疗等应用方面，而且在人类疾病建模和新药开发方面也是如此。特别是，从难治性疾病患者的体细胞中产生 iPS 细胞，并随后将其分化为受影响部位的细胞（例如神经元、心肌细胞、肝细胞和肌细胞），已经允许构建包含患者特异性遗传信息的疾病模型。例如，已经从患有神经精神障碍（包括精神分裂症和自闭症）以及患有神经退行性疾病（包括帕金森病和阿尔茨海默病）的患者中建立了疾病特异性 iPS 细胞。因此，对源自患者衍生 iPS 细胞的神经细胞进行多组学分析可能使研究人员能够阐明以前未知的神经疾病的发病机制。此外，目前正在使用疾病特异性 iPS 细胞对化学文库进行大规模筛选，预计将导致新药发现。因此，本综述概述了使用源自患者的 iPS 细胞进行神经障碍建模、测试现有药物和发现新药物的进展。通过将患者的体细胞重编程为 iPS 细胞，并将其分化为特定的细胞，从而可以在体外构建包含患者特异性遗传信息的疾病模型。此外，iPS 细胞上基因编辑技术的创新为阐明人类疾病的发病机制提供了新的方法。在这篇综述文章中，我们概述了神经疾病特异性 iPS 细胞研究的现状，并以实际例子的形式描述了最近获得的知识。
