Russo Fabiele B, Cugola Fernanda R, Fernandes Isabella R, Pignatari Graciela C, Beltrão-Braga Patricia C B
Fabiele B Russo, Fernanda R Cugola, Isabella R Fernandes, Graciela C Pignatari, Patricia C B Beltrão-Braga, Stem Cell Lab, Department of Surgery, School of Veterinary Medicine, University of São Paulo, São Paulo 05508-270, Brazil.
World J Transplant. 2015 Dec 24;5(4):209-21. doi: 10.5500/wjt.v5.i4.209.
Several diseases have been successfully modeled since the development of induced pluripotent stem cell (iPSC) technology in 2006. Since then, methods for increased reprogramming efficiency and cell culture maintenance have been optimized and many protocols for differentiating stem cell lines have been successfully developed, allowing the generation of several cellular subtypes in vitro. Gene editing technologies have also greatly advanced lately, enhancing disease-specific phenotypes by creating isogenic cell lines, allowing mutations to be corrected in affected samples or inserted in control lines. Neurological disorders have benefited the most from iPSC-disease modeling for its capability for generating disease-relevant cell types in vitro from the central nervous system, such as neurons and glial cells, otherwise only available from post-mortem samples. Patient-specific iPSC-derived neural cells can recapitulate the phenotypes of these diseases and therefore, considerably enrich our understanding of pathogenesis, disease mechanism and facilitate the development of drug screening platforms for novel therapeutic targets. Here, we review the accomplishments and the current progress in human neurological disorders by using iPSC modeling for Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal muscular atrophy, amyotrophic lateral sclerosis, duchenne muscular dystrophy, schizophrenia and autism spectrum disorders, which include Timothy syndrome, Fragile X syndrome, Angelman syndrome, Prader-Willi syndrome, Phelan-McDermid, Rett syndrome as well as Nonsyndromic Autism.
自2006年诱导多能干细胞(iPSC)技术发展以来,已经成功建立了多种疾病模型。从那时起,提高重编程效率和细胞培养维持的方法得到了优化,并且成功开发了许多分化干细胞系的方案,从而能够在体外生成多种细胞亚型。基因编辑技术最近也有了很大进展,通过创建同基因细胞系增强了疾病特异性表型,使得可以在受影响的样本中纠正突变或在对照系中插入突变。神经疾病从iPSC疾病模型中受益最大,因为它能够在体外从中枢神经系统生成与疾病相关的细胞类型,如神经元和神经胶质细胞,而这些细胞类型以前只能从死后样本中获得。患者特异性iPSC衍生的神经细胞可以重现这些疾病的表型,因此极大地丰富了我们对发病机制、疾病机理的理解,并促进了针对新型治疗靶点的药物筛选平台的开发。在此,我们回顾了利用iPSC模型对阿尔茨海默病、帕金森病、亨廷顿舞蹈病、脊髓性肌萎缩症、肌萎缩侧索硬化症、杜氏肌营养不良症、精神分裂症和自闭症谱系障碍(包括蒂莫西综合征、脆性X综合征、天使综合征、普拉德-威利综合征、费兰-麦克德米德综合征、雷特综合征以及非综合征性自闭症)进行人类神经疾病建模的成就和当前进展。