Modelling of Genetic Cardiac Diseases

Abstract

Cardiac disease modeling is crucial to improve our understanding of the mechanism of various cardiac diseases and to discover new therapeutic approaches. Several modeling methods such as animal and computer simulations have been used to elucidate the cardiac diseases’ mechanism and drug responses. However, each modeling technique has its own particular advantages and limitations. Human-based models would be particularly useful to investigate human cardiac diseases because humans and animals have differing cardiac physiologies and drug tolerability. In addition, the phenotype of cardiac diseases and response to therapeutic intervention differ not only between mutations but also among patients. Therefore, such diseases strongly demand the individualized/personalized strategies. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) offer the striking feature of retain-ing the same genetic information as donor, which guide us to investigate diseases and predict response to drug treatment individually. This feature of hiPSC-CMs is superior to the conventional in vitro modeling of cardiac diseases. Thus far, hiPSC-CMs have been successfully recapitulated many monogenic and also complex genetic cardiac diseases. hiPSC-CMs could be differentiated into different types of cardiomyocytes and non-cardiomyocyte cells, which empower us to understand cardiac chamber-specific arrhythmias such as atrial fibrillation and ventricular tachycardia.