iPSC-derived cardiomyocytes for personalized medicine- promises and challenges.

Abstract

Human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have revolutionized cardiac research and medicine by offering patient-specific platforms for disease modeling, drug discovery, and regenerative therapies. The ability of iPSC-CMs to replicate key aspects of human cardiac physiology makes them invaluable for studying genetic disorders, evaluating cardiotoxicity, and guiding therapeutic interventions. However, a persistent challenge limiting their clinical and translational utility is their structural and functional immaturity, as iPSC-CMs often retain fetal-like characteristics rather than adult cardiomyocyte properties. This review examines the diverse applications of iPSC-CMs in both preclinical and clinical research, emphasizing their role in modeling inherited cardiac diseases, screening drugs for cardiotoxicity, and advancing personalized medicine. It also explores current maturation strategies including biochemical, biophysical, and bioengineering approaches designed to enhance electrophysiological function, contractile performance, and metabolic maturation. The review further proposes a framework for standardized iPSC-CMs maturity assessment that integrates transcriptomic, structural, electrophysiological, metabolic, and functional parameters against adult cardiomyocyte reference standards. In addition, the review addresses critical considerations such as scalability, standardization, and regulatory frameworks, which are essential for the successful translation of iPSC-CMs from the bench to the bedside. By overcoming these limitations, iPSC-CMs hold the potential to transform cardiovascular research, enabling the development of more effective regenerative therapies and accelerating the progress of precision medicine.