Richard Jean-Philippe, Maragakis Nicholas J
Johns Hopkins University, School of Medicine, USA.
Johns Hopkins University, School of Medicine, USA.
Brain Res. 2015 May 14;1607:15-25. doi: 10.1016/j.brainres.2014.09.017. Epub 2014 Sep 16.
The ability to reprogram adult somatic cells into pluripotent stem cells that can differentiate into all three germ layers of the developing human has fundamentally changed the landscape of biomedical research. For a neurodegenerative disease like Amyotrophic Lateral Sclerosis (ALS), which does not manifest itself until adulthood and is a heterogeneous disease with few animal models, this technology may be particularly important. Induced pluripotent stem cells (iPSC) have been created from patients with several familial forms of ALS as well as some sporadic forms of ALS. These cells have been differentiated into ALS-relevant cell subtypes including motor neurons and astrocytes, among others. ALS-relevant pathologies have also been identified in motor neurons from these cells and may provide a window into understanding disease mechanisms in vitro. Given that this is a relatively new field of research, numerous challenges remain before iPSC methodologies can fulfill their potential as tools for modeling ALS as well as providing a platform for the investigation of ALS therapeutics. This article is part of a Special Issue entitled ALS complex pathogenesis.
将成人体细胞重编程为多能干细胞，使其能够分化为发育中的人类的所有三个胚层，这一能力从根本上改变了生物医学研究的格局。对于像肌萎缩侧索硬化症（ALS）这样的神经退行性疾病来说，这种技术可能尤为重要。ALS直到成年才会显现，并且是一种异质性疾病，动物模型很少。已经从几种家族性形式的ALS患者以及一些散发性形式的ALS患者中创建了诱导多能干细胞（iPSC）。这些细胞已经分化为与ALS相关的细胞亚型，包括运动神经元和星形胶质细胞等。在这些细胞的运动神经元中也发现了与ALS相关的病理特征，这可能为在体外理解疾病机制提供一个窗口。鉴于这是一个相对较新的研究领域，在iPSC方法能够充分发挥其作为ALS建模工具的潜力以及为ALS治疗研究提供平台之前，仍然存在许多挑战。本文是名为“ALS复杂发病机制”的特刊的一部分。
