Heart disease is a global health problem; finding effective therapies is therefore critical. An incomplete understanding of heart disease’s underlying biological mechanisms has stalled novel therapies’ journey to clinical care. Limited access to suitable experimental human models has exacerbated these mechanistic knowledge gaps and thus hindered new therapeutic discoveries. New drugs have also failed due to safety. Current approaches to develop novel therapies and predict cardiotoxicity rely on animal models with species-specific properties that may not translate to humans. More specifically, access to human cardiomyocytes to investigate disease mechanisms or test new drugs is limited by multiple factors: acquiring human heart tissue is challenging, and the cells are short-lived and do not proliferate. However, human induced pluripotent stem cells (hiPSC) provide a nearly limitless supply of human cardiomyocytes.

HiPSC are adult (differentiated) cells reprogrammed into an embryonic-like state. Self-renewing and pluripotent, they can be differentiated into other cell types, including cardiomyocytes. Although their fetal-like properties require multiple strategies to enhance maturation, these human cardiomyocytes are an important cell source for disease modeling. Cells derived from hiPSC can be used in multiple aspects of cardiovascular research and medicine: to understand the pathophysiology and genetic underpinnings of cardiac diseases, to assess drugs, to screen for cardiotoxicity screening, and to support cell therapy. Within personalized medicine, hiPSC technology can generate autologous cells for investigating inherited heart diseases and conducting personalized drug safety tests to predict adverse reactions. Furthermore, using hiPSC as the main cell source, we can engineer human cardiac tissues that reproduce key functional characteristics of inherited and acquired cardiomyopathies.