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Adv Exp Med Biol. 2019;1175:383-405. doi: 10.1007/978-981-13-9913-8_15.
Despite over a century of research into Alzheimer's disease (AD), progress in understanding the complex aetiology has been hindered, in part, by a lack of human, disease relevant, cellular models, reflected in an inability to translate results from animal studies to successful human therapies. Induced pluripotent stem cell (iPSC) technology, in which somatic cells are reprogrammed to pluripotent stem cells, creates an ideal physiologically relevant model as they maintain the genetic identity of the donor. These iPSCs can self-renew indefinitely in vitro and have the capacity to differentiate into any cell type, opening up new discovery and therapeutic opportunities. Despite a plethora of publications indicating the generation and utility of iPSC-derived neurones for disease modelling to date, in comparison only a limited number of studies have described generation of enriched astroglia from patients with early- or late-stage onset of AD. We recently reported that iPSC-astroglia derived from these patients are capable of mimicking a wide variety of deficits in homeostatic molecular cascades, intimately associated with AD, that are routinely observed in vivo. This review examines the opportunities and limitations of this innovative technology in the context of AD modelling and uses for preclinical discovery to improve our success for an efficacious therapeutic outcome.
尽管对阿尔茨海默病（AD）的研究已经进行了一个多世纪，但由于缺乏人类、与疾病相关的细胞模型，对其复杂病因的理解进展一直受到阻碍，这反映在无法将动物研究的结果转化为成功的人类疗法上。诱导多能干细胞（iPSC）技术可将体细胞重编程为多能干细胞，创造了一个理想的生理相关模型，因为它们保持了供体的遗传身份。这些 iPSC 可以在体外无限自我更新，并具有分化为任何细胞类型的能力，为新的发现和治疗机会开辟了道路。尽管有大量出版物表明迄今为止已经生成并利用 iPSC 衍生神经元进行疾病建模，但与这一数量相比，只有有限的研究描述了从 AD 早发或晚发患者中生成富含星形胶质细胞的方法。我们最近报告称，这些患者来源的 iPSC-星形胶质细胞能够模拟与 AD 密切相关的各种与内稳态分子级联相关的缺陷，这些缺陷在体内通常可以观察到。这篇综述探讨了该创新技术在 AD 建模和用于临床前发现以提高有效治疗效果方面的机会和局限性。
