Center of Medical Genetics, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, 2650 Antwerp, Belgium.
Department of Cardiology, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, 2610 Antwerp, Belgium.
Int J Mol Sci. 2021 Mar 10;22(6):2825. doi: 10.3390/ijms22062825.
Brugada syndrome (BrS) is an inherited cardiac arrhythmia that predisposes to ventricular fibrillation and sudden cardiac death. It originates from oligogenic alterations that affect cardiac ion channels or their accessory proteins. The main hurdle for the study of the functional effects of those variants is the need for a specific model that mimics the complex environment of human cardiomyocytes. Traditionally, animal models or transient heterologous expression systems are applied for electrophysiological investigations, each of these models having their limitations. The ability to create induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), providing a source of human patient-specific cells, offers new opportunities in the field of cardiac disease modelling. Contemporary iPSC-CMs constitute the best possible in vitro model to study complex cardiac arrhythmia syndromes such as BrS. To date, thirteen reports on iPSC-CM models for BrS have been published and with this review we provide an overview of the current findings, with a focus on the electrophysiological parameters. We also discuss the methods that are used for cell derivation and data acquisition. In the end, we critically evaluate the knowledge gained by the use of these iPSC-CM models and discuss challenges and future perspectives for iPSC-CMs in the study of BrS and other arrhythmias.
Brugada 综合征（BrS）是一种遗传性心律失常，易导致心室颤动和心源性猝死。它源于影响心脏离子通道或其辅助蛋白的寡基因改变。研究这些变体的功能影响的主要障碍是需要一个模拟人类心肌细胞复杂环境的特定模型。传统上，动物模型或瞬时异源表达系统用于电生理研究，这些模型各有其局限性。诱导多能干细胞衍生心肌细胞（iPSC-CMs）的创建能力，为提供患者特异性细胞的来源，为心脏疾病建模领域提供了新的机会。目前，已经有 13 篇关于 BrS 的 iPSC-CM 模型的报告，通过本篇综述，我们提供了当前研究结果的概述，重点介绍了电生理参数。我们还讨论了用于细胞衍生和数据采集的方法。最后，我们批判性地评估了使用这些 iPSC-CM 模型获得的知识，并讨论了在研究 BrS 和其他心律失常中使用 iPSC-CMs 的挑战和未来展望。
