Wen Zhexing, Christian Kimberly M, Song Hongjun, Ming Guo-li
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Curr Opin Neurobiol. 2016 Feb;36:118-27. doi: 10.1016/j.conb.2015.11.003. Epub 2015 Dec 17.
Psychiatric disorders are heterogeneous disorders characterized by complex genetics, variable symptomatology, and anatomically distributed pathology, all of which present challenges for effective treatment. Current treatments are often blunt tools used to ameliorate the most severe symptoms, often at the risk of disrupting functional neural systems, thus there is a pressing need to develop rational therapeutics. Induced pluripotent stem cells (iPSCs) reprogrammed from patient somatic cells offer an unprecedented opportunity to recapitulate both normal and pathologic human tissue and organ development, and provides new approaches for understanding disease mechanisms and for drug discovery with higher predictability of their effects in humans. Here we review recent progress and challenges in using human iPSCs for modeling neuropsychiatric disorders and developing novel therapeutic strategies.
精神疾病是异质性疾病,其特征在于复杂的遗传学、多变的症状学以及解剖学上分布的病理学,所有这些都给有效治疗带来了挑战。当前的治疗方法往往是用于缓解最严重症状的简单手段,常常有破坏功能性神经系统的风险,因此迫切需要开发合理的治疗方法。从患者体细胞重编程而来的诱导多能干细胞(iPSC)为再现正常和病理性人类组织及器官发育提供了前所未有的机会,并为理解疾病机制和药物发现提供了新方法,其对人类的影响具有更高的可预测性。在此,我们综述了利用人类iPSC对神经精神疾病进行建模以及开发新型治疗策略方面的最新进展和挑战。