Ordoñez M Paulina, Steele John W
Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA 92037, United States; Department of Pediatric Gastroenterology, Hepatology, and Nutrition, University of California, San Diego, La Jolla, CA 92037, United States.
Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA 92037, United States.
Brain Res. 2017 Feb 1;1656:63-67. doi: 10.1016/j.brainres.2016.03.007. Epub 2016 Mar 10.
Data generated in Niemann Pick type C1 (NPC1) human embryonic and human induced pluripotent stem cell derived neurons complement on-going studies in animal models and provide the first example, in disease-relevant human cells, of processes that underlie preferential neuronal defects in a NPC1. Our work and that of other investigators in human neurons derived from stem cells highlight the importance of performing rigorous mechanistic studies in relevant cell types to guide drug discovery and therapeutic development, alongside of existing animal models. Through the use of human stem cell-derived models of disease, we can identify and discover or repurpose drugs that revert early events that lead to neuronal failure in NPC1. Together with the study of disease pathogenesis and efficacy of therapies in animal models, these strategies will fulfill the promise of stem cell technology in the development of new treatments for human diseases. This article is part of a Special Issue entitled SI: Exploiting human neurons.
在尼曼匹克C1型(NPC1)人类胚胎干细胞和人类诱导多能干细胞衍生神经元中产生的数据补充了正在进行的动物模型研究,并在与疾病相关的人类细胞中首次展示了NPC1中优先神经元缺陷所依据的过程。我们的工作以及其他研究人员在源自干细胞的人类神经元方面的工作强调了在相关细胞类型中进行严格的机制研究对于指导药物发现和治疗开发的重要性,与现有的动物模型一起。通过使用人类干细胞衍生的疾病模型,我们可以识别、发现或重新利用能够逆转导致NPC1中神经元功能衰竭的早期事件的药物。结合在动物模型中对疾病发病机制和治疗效果的研究,这些策略将实现干细胞技术在开发人类疾病新疗法方面的前景。本文是名为“利用人类神经元”特刊的一部分。