Abstract Body:

Background: Myocardial infarction (MI) leads to irreversible cardiomyocyte loss, triggering adverse remodeling and heart failure. Traditional pharmacologic and surgical approaches fail to regenerate lost myocardium, necessitating innovative regenerative therapies. Stem cell-based interventions, particularly mesenchymal stromal cells (MSCs) and induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), have shown potential in cardiac repair. However, issues related to low engraftment, immune rejection, and electrical integration remain critical challenges limiting clinical translation.

Methods: This review synthesizes recent preclinical and clinical evidence on mesenchymal stromal cells and induced pluripotent stem cell-derived cardiomyocytes for cardiac regeneration, analyzing their mechanisms, efficacy, and limitations. Additionally, emerging strategies, including biomaterial scaffolds, 3D bioprinting, exosome-mediated repair, and cell combinations, are discussed to enhance therapeutic efficacy.

Results: MSCs primarily exert cardioprotective effects via paracrine signaling, modulating the inflammation and fibrosis, whereas iPSC-CMs facilitate remuscularization but pose risks of arrhythmias and tumorigenicity. Cardiac patches integrating biomaterials with stem cells improve the cell retention and functional outcomes. Clinical trials have provided mixed results, with some demonstrating enhanced ejection fraction and infarct size reduction, while the others reveal limited long-term benefits.

Conclusion: Stem cell-derived cardiac patches, combined with biomaterial engineering and precision medicine, offer a a very promising approach to myocardial regeneration. However, optimizing the cell survival, immune tolerance, and the electrical coupling remains challenging. Future research should focus on scalable, personalized, and minimally invasive applications to accelerate clinical adoption.