Chapter 10 - Induced pluripotent stem cells for modeling of cardiac arrhythmias

Abstract

Arrhythmias are a critical health burden, responsible for a significant proportion of sudden cardiac death. They arise from inherited or acquired abnormalities in cardiac ion channels or their associated regulatory proteins functioning within cardiomyocytes. In opposite with the classical in vitro models, human induced pluripotent stem cells–derived cardiomyocytes (hiPSC-CMs) offer a patient-specific model that recapitulates disease phenotype and mirrors the reaction to pharmacotherapy. Thus far, the hiPSC-CMs model has genuinely improved our knowledge concerning both, the pathogenicity of genetic variants in inherited arrhythmias and the toxicity of some factors implicated in acquired forms of arrhythmia. Besides, as these cells preserve patient genetic background, they enable the customization of therapies and open thereby the door for personalized medicine. In this chapter, we will outline studies that leveraged the hiPSC-CMs model to explore the mechanism underlying inherited or acquired arrhythmic phenotypes and will point out its sustained limits.