McKinney Cindy E
iPSC Lab/Edward Via College of Osteopathic Medicine and The Gibbs Research Institute, Spartanburg, SC, USA.
Neural Regen Res. 2017 Jul;12(7):1062-1067. doi: 10.4103/1673-5374.211180.
The ability to use induced pluripotent stem cells (iPSC) to model brain diseases is a powerful tool for unraveling mechanistic alterations in these disorders. Rodent models of brain diseases have spurred understanding of pathology but the concern arises that they may not recapitulate the full spectrum of neuron disruptions associated with human neuropathology. iPSC derived neurons, or other neural cell types, provide the ability to access pathology in cells derived directly from a patient's blood sample or skin biopsy where availability of brain tissue is limiting. Thus, utilization of iPSC to study brain diseases provides an unlimited resource for disease modelling but may also be used for drug screening for effective therapies and may potentially be used to regenerate aged or damaged cells in the future. Many brain diseases across the spectrum of neurodevelopment, neurodegenerative and neuropsychiatric are being approached by iPSC models. The goal of an iPSC based disease model is to identify a cellular phenotype that discriminates the disease-bearing cells from the control cells. In this mini-review, the importance of iPSC cell models validated for pluripotency, germline competency and function assessments is discussed. Selected examples for the variety of brain diseases that are being approached by iPSC technology to discover or establish the molecular basis of the neuropathology are discussed.
利用诱导多能干细胞(iPSC)建立脑部疾病模型的能力,是揭示这些疾病机制性改变的有力工具。脑部疾病的啮齿动物模型推动了对病理学的理解,但人们担心它们可能无法完全重现与人类神经病理学相关的神经元破坏的全貌。iPSC衍生的神经元或其他神经细胞类型,使得在脑组织获取受限的情况下,能够直接从患者的血液样本或皮肤活检中获取的细胞里研究病理学。因此,利用iPSC研究脑部疾病为疾病建模提供了无限资源,还可用于有效疗法的药物筛选,并且未来可能用于再生衰老或受损细胞。iPSC模型正在研究神经发育、神经退行性和神经精神疾病等各类脑部疾病。基于iPSC的疾病模型的目标是识别一种细胞表型,以区分患病细胞和对照细胞。在本综述中,讨论了经过多能性、种系能力和功能评估验证的iPSC细胞模型的重要性。还讨论了利用iPSC技术研究各类脑部疾病以发现或确立神经病理学分子基础的一些实例。