Molecular Regulation of Cardiomyocyte Maturation

This review aims to discuss the process of cardiomyocyte maturation, with a focus on the underlying molecular mechanisms required to form a fully functional heart. We examine both long-standing concepts associated with cardiac maturation and recent developments, and the overall complexity of molecularly integrating all the processes that lead to a mature heart.

Cardiac maturation, defined here as the sequential changes that occurring before the heart reaches full maturity, has been a subject of investigation for decades. Recently, there has been a renewed, highly focused interest in this process, driven by clinically motivated research areas where enhancing maturation may lead to improved therapeutic opportunities. These include using pluripotent stem cell models for cell therapy and disease modeling, as well as recent advancements in adult cardiac regeneration approaches. We highlight key processes underlying maturation of the heart, including cellular and organ growth, and electrophysiological, metabolic, and contractile maturation. We further discuss how these processes integrate and interact to contribute to the overall complexity of the developing heart. Finally, we emphasize the transformative potential for translating relevant maturation concepts to emerging models of heart disease and regeneration.