Department of Histology and Embryology, Faculty of Medicine, Masaryk University Brno, Brno, Czech Republic.
International Clinical Research Center, St. Anne's Faculty Hospital Brno, Brno, Czech Republic.
Stem Cell Rev Rep. 2022 Feb;18(2):792-820. doi: 10.1007/s12015-021-10254-3. Epub 2022 Feb 2.
During the past two decades, induced pluripotent stem cells (iPSCs) have been widely used to study mechanisms of human neural development, disease modeling, and drug discovery in vitro. Especially in the field of Alzheimer's disease (AD), where this treatment is lacking, tremendous effort has been put into the investigation of molecular mechanisms behind this disease using induced pluripotent stem cell-based models. Numerous of these studies have found either novel regulatory mechanisms that could be exploited to develop relevant drugs for AD treatment or have already tested small molecules on in vitro cultures, directly demonstrating their effect on amelioration of AD-associated pathology. This review thus summarizes currently used differentiation strategies of induced pluripotent stem cells towards neuronal and glial cell types and cerebral organoids and their utilization in modeling AD and potential drug discovery.
在过去的二十年中,诱导多能干细胞(iPSCs)已被广泛用于研究人类神经发育的机制、疾病建模以及体外药物发现。特别是在缺乏这种治疗方法的阿尔茨海默病(AD)领域,人们投入了大量精力,使用基于诱导多能干细胞的模型来研究这种疾病背后的分子机制。许多研究发现了新的调控机制,这些机制可以被开发利用来治疗 AD,或者已经在体外培养物上测试了小分子药物,直接证明了它们对改善 AD 相关病理的效果。因此,本综述总结了目前用于诱导多能干细胞向神经元和神经胶质细胞类型以及脑类器官分化的策略,以及它们在 AD 建模和潜在药物发现中的应用。