Features of cardiomyocyte proliferation and its potential for cardiac regeneration

The human heart does not regenerate. Instead, following injury, human hearts scar. The loss of contractile tissue contributes significantly to morbidity and mortality. In contrast to humans, zebrafish and newts faithfully regenerate their hearts. Interestingly, regeneration is in both cases based on cardiomyocyte proliferation. In addition, mammalian cardiomyocytes proliferate during foetal development. Their proliferation reaches its maximum around chamber formation, stops shortly after birth, and subsequent heart growth is mostly achieved by an increase in cardiomyocyte size (hypertrophy). The underlying mechanisms that regulate cell cycle arrest and the switch from proliferation to hypertrophy are unclear. In this review, we highlight features of dividing cardiomyocytes, summarize the attempts to induce mammalian cardiomyocyte proliferation, critically discuss methods commonly used for its detection, and explore the potential and problems of inducing cardiomyocyte proliferation to improve function in diseased hearts.