Benjamin B Johnson, Christine L Mummery, Richard P Davis
Myocardial infarction (MI) remains a leading cause of death worldwide, and therapies that limit injury, promote repair, and restore cardiac function remain limited. Human induced pluripotent stem cells (hiPSCs) provide a renewable source of patient-specific cardiac cells and have enabled the development of increasingly complex in vitro models that incorporate cardiomyocytes together with supporting stromal and vascular cell types. These models are now being used to study multiple stages of MI pathophysiology and are increasingly being applied in therapeutic discovery and regenerative strategies. In this review, we summarize hiPSC-based cardiac models spanning 2D cultures to advanced 3D tissues, organoids, and heart-on-chip systems, evaluating how well they capture key features of human MI. We further discuss hiPSC applications in therapeutic discovery, drug screening, precision medicine, and regenerative repair. Finally, we highlight priorities for the field, including improved physiological complexity, stronger translational robustness, bioengineering strategies, and integration with multi-omics.