Since the discovery of the induced pluripotent stem cell (iPSC) technique more than a decade ago, extensive progress has been made to develop clinically relevant cell culture systems. Alzheimer’s disease (AD) is the most common neurodegenerative disease, accounting for approximately two thirds of all cases of dementia. The massively increasing number of affected individuals explains the major interest of research in this disease as well as the strong need for better understanding of disease mechanisms. IPSC-derived neural cells have been widely used to recapitulating key aspects of AD. In this Review we highlight the progress made in studying AD pathophysiology and address the currently available techniques, such as specific differentiation techniques for AD-relevant cell types as well as 2D and 3D cultures. Finally, we critically discuss the key challenges and future directions of this field and how some of the major limitations of the iPSC technique may be overcome. Stem cell-based disease models have the potential to induce a paradigm shift in biomedical research. In particular, the combination of the iPSC technology with recent advances in gene editing or 3D cell cultures represents a breakthrough for in vitro disease modeling and provides a platform for a better understanding of disease mechanisms in human cells and the discovery of novel therapeutics.

中文翻译：

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培养皿中的阿尔茨海默氏症——基于诱导多能干细胞的疾病建模

自十多年前发现诱导多能干细胞 (iPSC) 技术以来，在开发临床相关细胞培养系统方面取得了广泛进展。阿尔茨海默病 (AD) 是最常见的神经退行性疾病，约占所有痴呆病例的三分之二。大量增加的受影响个体解释了对这种疾病研究的主要兴趣以及对更好地了解疾病机制的强烈需求。IPSC 衍生的神经细胞已被广泛用于概括 AD 的关键方面。在这篇综述中，我们重点介绍了在研究 AD 病理生理学方面取得的进展，并讨论了目前可用的技术，例如针对 AD 相关细胞类型以及 2D 和 3D 培养物的特定分化技术。最后，我们批判性地讨论了该领域的关键挑战和未来方向，以及如何克服 iPSC 技术的一些主要限制。基于干细胞的疾病模型有可能引发生物医学研究的范式转变。特别是，iPSC 技术与基因编辑或 3D 细胞培养的最新进展相结合，代表了体外疾病建模的突破，并为更好地了解人类细胞中的疾病机制和发现新疗法提供了平台。