Laboratory of Chromatin and Human Disease, Key Laboratory of Regenerative Biology of the Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Guangzhou 510530, China.
Drug Discovery Pipeline Group, Guangzhou Institutes of Biomedicine and Health, Guangzhou 510530, China.
Exp Biol Med (Maywood). 2014 Nov;239(11):1421-32. doi: 10.1177/1535370214538588. Epub 2014 Jun 17.
The prevalence and incidence of Parkinson's disease (PD) is increasing due to a prolonged life expectancy. This highlights the need for a better mechanistic understanding and new therapeutic approaches. However, traditional in vitro and in vivo experimental models to study PD are suboptimal, thus hampering the progress in the field. The epigenetic reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) offers a unique way to overcome this problem, as these cells share many properties of embryonic stem cells (ESCs) including the potential to be transformed into different lineages. PD modeling with iPSCs is nowadays facilitated by the growing availability of high-efficiency neural-specific differentiation protocols and the possibility to correct or induce mutations as well as creating marker cell lines using designer nucleases. These technologies, together with steady advances in human genetics, will likely introduce profound changes in the way we interpret PD and develop new treatments. Here, we summarize the different PD iPSCs reported so far and discuss the challenges for disease modeling using these cell lines.
由于预期寿命的延长,帕金森病 (PD) 的患病率和发病率正在上升。这凸显了对更好的机制理解和新治疗方法的需求。然而,用于研究 PD 的传统体外和体内实验模型并不理想,从而阻碍了该领域的进展。体细胞的表观遗传重编程为诱导多能干细胞 (iPSC) 提供了一种独特的克服此问题的方法,因为这些细胞与胚胎干细胞 (ESC) 具有许多共同特性,包括转化为不同谱系的潜力。随着高效的神经特异性分化方案的不断普及以及使用设计的核酸酶进行突变的纠正或诱导的可能性的出现,iPSC 对 PD 的建模变得更加容易。这些技术,再加上人类遗传学的稳步进步,可能会对我们解释 PD 和开发新治疗方法的方式产生深远的影响。在这里,我们总结了迄今为止报道的不同 PD iPSC,并讨论了使用这些细胞系进行疾病建模的挑战。