From potential to practice: Overcoming the immaturity of iPSC-derived cardiomyocytes for regenerative medicine

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) hold great promise for revolutionizing regenerative medicine. Preclinical studies indicate their potential to repair damaged myocardial tissue in animal models of heart disease. Despite ongoing advances in the field, the incomplete maturation of iPSC-CMs remains a critical barrier that significantly hinders their translation into clinical applications. The maturation of cardiomyocytes is crucial for the successful integration of iPSC-CMs into damaged heart tissue. Compared to adult cells, immature CMs have impaired structural characteristics, contractile function, and electrophysiological properties. Recent studies have focused on identifying key factors, such as altered cell metabolic pathways or mechanical and electrical stimulation, that may promote iPSC-CM maturation. Progress in this area has profound implications for the development of personalized disease models and cell therapies that promote the regeneration and repair of damaged heart tissue. This review describes the current achievements in the application of regenerative medicine using iPSC-CM and tissue engineering, highlighting the molecular mechanisms, culture strategies, and biophysical approaches that have contributed to improved maturation of these cells. Numerous studies are currently being carried out using both in vitro and in vivo models to better understand the complex mechanism of regeneration of the damaged heart. The combination of stem cell therapy and 3D cardiac cell cultures aims to repair and regenerate damaged cardiac tissue more effectively.