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诱导多能干细胞衍生的心肌细胞在遗传性心律失常中的作用:发病机制探索与药物研发

iPSC-Derived Cardiomyocytes in Inherited Cardiac Arrhythmias: Pathomechanistic Discovery and Drug Development.

作者信息

Simons Eline, Loeys Bart, Alaerts Maaike

机构信息

Cardiogenetics Research Group, Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, 2650 Antwerp, Belgium.

出版信息

Biomedicines. 2023 Jan 25;11(2):334. doi: 10.3390/biomedicines11020334.

Abstract

With the discovery of induced pluripotent stem cell (iPSCs) a wide range of cell types, including iPSC-derived cardiomyocytes (iPSC-CM), can now be generated from an unlimited source of somatic cells. These iPSC-CM are used for different purposes such as disease modelling, drug discovery, cardiotoxicity testing and personalised medicine. The 2D iPSC-CM models have shown promising results, but they are known to be more immature compared to in vivo adult cardiomyocytes. Novel approaches to create 3D models with the possible addition of other (cardiac) cell types are being developed. This will not only improve the maturity of the cells, but also leads to more physiologically relevant models that more closely resemble the human heart. In this review, we focus on the progress in the modelling of inherited cardiac arrhythmias in both 2D and 3D and on the use of these models in therapy development and drug testing.

摘要

随着诱导多能干细胞(iPSC)的发现,现在可以从无限的体细胞来源生成包括iPSC衍生的心肌细胞(iPSC-CM)在内的多种细胞类型。这些iPSC-CM被用于不同目的,如疾病建模、药物发现、心脏毒性测试和个性化医疗。二维iPSC-CM模型已显示出有前景的结果,但已知它们与体内成年心肌细胞相比更不成熟。正在开发创建三维模型并可能添加其他(心脏)细胞类型的新方法。这不仅会提高细胞的成熟度,还会产生更接近生理状态、更类似于人类心脏的模型。在这篇综述中,我们重点关注二维和三维遗传性心律失常建模的进展以及这些模型在治疗开发和药物测试中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afee/9953535/23f21c36d66f/biomedicines-11-00334-g001.jpg

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