Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hiPSC-CMs) as a Platform for Modeling Arrhythmias

Cardiac arrhythmias can arise due to a host of both genetic and acquired factors. Specifically, the genetic basis of arrhythmogenesis is not fully understood due to the lack of robust models that reliably recapitulate human physiology. Humaninduced pluripotent stem cells (hiPSCs) have strengthened regenerative medicine by producing cells that bear the genetic signature of patients being studied. Upon differentiation into hiPSC-derived cardiomyocytes (hiPSC-CMs), these cells can be used to phenotype known mutations or suspected variants that may contribute to abnormal electrical activity in the heart. Furthermore, novel therapeutics can be screened for the management and treatment of arrhythmias in patient-specific hiPSC-CMs. In this chapter, we will briefly discuss the practical utility of hiPSCCMs to study inherited arrhythmias with a specific focus on atrial fibrillation (AF), catecholaminergic polymorphic ventricular tachycardia (CPVT), and disruptive electrical events that may occur in patients with hypertrophic cardiomyopathy (HCM). We will describe an investigative pipeline that integrates genome editing, tissue engineering, biobanking, and systems biology as complementary approaches. Together, these various applications are directed toward a common goal of bench-to-bedside characterization of arrhythmias in patient-specific hiPSC-CMs.