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Dissecting Alzheimer’s disease pathogenesis in human 2D and 3D models
Molecular and Cellular Neuroscience ( IF 3.5 ) Pub Date : 2020-10-14 , DOI: 10.1016/j.mcn.2020.103568
Giovanna Cenini 1 , Matthias Hebisch 2 , Vira Iefremova 1 , Lea J Flitsch 1 , Yannik Breitkreuz 3 , Rudolph E Tanzi 2 , Doo Yeon Kim 2 , Michael Peitz 4 , Oliver Brüstle 1
Affiliation  

The incidence of Alzheimer’s disease (AD) is increasing with the aging population, and it has become one of the main health concerns of modern society. The dissection of the underlying pathogenic mechanisms and the development of effective therapies remain extremely challenging, also because available animal and cell culture models do not fully recapitulate the whole spectrum of pathological changes. The advent of human pluripotent stem cells and cell reprogramming has provided new prospects for tackling these challenges in a human and even patient-specific setting. Yet, experimental modeling of non-cell autonomous and extracellular disease-related alterations has remained largely inaccessible. These limitations are about to be overcome by advances in the development of 3D cell culture systems including organoids, neurospheroids and matrix-embedded 3D cultures, which have been shown to recapitulate extracellular pathologies such as plaque formation in vitro. Recent xenograft studies have even taken human stem cell-based disease modeling to an in vivo scenario where grafted neurons are probed in a disease background in the context of a rodent brain. Here, we review the latest developments in this emerging field along with their advantages, challenges, and future prospects.



中文翻译:

在人类 2D 和 3D 模型中剖析阿尔茨海默病的发病机制

随着人口老龄化,阿尔茨海默病(AD)的发病率不断增加,已成为现代社会关注的主要健康问题之一。潜在致病机制的剖析和有效疗法的开发仍然极具挑战性,这也是因为可用的动物和细胞培养模型不能完全概括病理变化的整个范围。人类多能干细胞和细胞重编程的出现为在人类甚至患者特定环境中应对这些挑战提供了新的前景。然而,非细胞自主和细胞外疾病相关改变的实验模型在很大程度上仍然无法获得。随着 3D 细胞培养系统(包括类器官、体外。最近的异种移植研究甚至将基于人类干细胞的疾病建模应用于体内场景,在啮齿动物大脑的背景下,在疾病背景中探测移植神经元。在这里,我们回顾了这一新兴领域的最新发展及其优势、挑战和未来前景。

更新日期:2020-10-15
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