From the Laboratory to the Clinic: Differentiation, Disease Modeling and Transplantation of Cardiac Organoids

Cardiac organoids (hiPSC-COs), an emerging novel methodology, simulate human cardiac development and disease progression, providing a powerful in vitro model for cardiovascular research. This study systematically reviews the progress of translational research on cardiac organoids from laboratory to clinical applications. It focuses on two major construction strategies: first, the self-organizing differentiation based on embryoid bodies can reproduce multi-lineage cardiac structures and is suitable for studies of developmental abnormalities such as congenital heart diseases; second, the modular assembly scheme demonstrates high customizability through the precise combination of pre-differentiated cell types in constructing specific pathological models (such as arrhythmia and MI). This study further summarizes its application value in modeling heart diseases driven by environmental factors (such as cryogenic damage and hypoxia) and genetic factors, as well as in screening drug-induced cardiotoxicity. It also analyzes the potential and clinical transformation challenges, such as immune rejection and tumorigenicity, in the transplantation of iPSC-based cardiac organoids in terms of vascularization integration and recovery of electrical coupling function. Finally, this study provides a roadmap for the development of next-generation cardiac organoids for drug discovery, precision medicine, and regenerative medicine.