Human cardiac drug discovery and disease modeling face challenges in recapitulating cellular complexity and animal‐to‐human translation due to the limitations of conventional 2D cell culture and animal models. The development of human cardiac organoid technologies could help in stimulating and maintaining differentiated cell functions for extended periods of time. By closely mimicking in vivo organ functions in vitro they could thereby help in overcoming the obstacles mentioned above. Through the construction of human cardiac organoids from pluripotent stem cell–derived cells, derived from patients with specific known genotypes and phenotypes, more complex and robust in vitro tools have recently become available for disease modeling. In this review, we will describe the relevance and importance of evolving organoid platforms in disease biology. We further provide examples of cardiac organoid platforms, which may lead the way toward future personalized medicine and drug discovery.

Genetic cardiomyopathies are characterized by changes in the function and structure of the myocardium. The development of a novel in vitro model could help to better emulate healthy and diseased human heart conditions and may improve the understanding of disease mechanisms. In this study, for the first time, we demonstrated the generation of cardiac organoids using a triculture approach of human induced pluripotent stem-cell-derived cardiomyocytes (hiPS-CMs)—from healthy subjects and cardiomyopathy patients—human cardiac microvascular endothelial cells (HCMECs) and human cardiac fibroblasts (HCFs). We assessed the organoids’ suitability as a 3D cellular model for the representation of phenotypical features of healthy and cardiomyopathic hearts. We observed clear differences in structure and beating behavior between the organoid groups, depending on the type of hiPS-CMs (healthy versus cardiomyopathic) used. Organoids may thus prove a promising tool for the design and testing of patient-specific treatments as well as provide a platform for safer and more efficacious drug development.