Modeling long QT syndromes using induced pluripotent stem cells: Current progress and future challenges

Long QT syndromes (LQTS) are a family of inherited monogenetic disorders caused by gain or loss-of-function mutations of cardiac ion channels and are characterized by a prolonged QT interval in the ECG. The disease-specific mutations lead to prolonged action potential durations and early after-depolarizations in cardiomyocytes potentially giving rise to triggered extrabeats and life-threatening arrhythmias in patients. The generation of induced pluripotent stem cells from somatic cells of patients and their differentiation into cardiomyocytes represents a powerful method enabling the investigation of disease-specific cardiomyocytes. In this review we highlight the latest progress in the generation of long QT syndrome-specific induced pluripotent stem cells and cardiomyocytes to investigate the disease in vitro. We also point out future challenges that need to be addressed to allow drug screening using patient-specific cardiomyocytes.