Zebrafish as a Model for Studying Cardiac Regeneration

Abstract

Heart failure caused by cardiomyocyte loss after ischemic tissue damage is a leading cause of death worldwide. Although adult mammalian cardiomyocytes are able to proliferate during normal aging and after infarction, they do so at insufficient rates for effective cardiac regeneration. Likewise, none of several described cardiac stem cell populations appear to form significant numbers of cardiomyocytes in ischemic hearts. Thus, adult mammals cannot regenerate heart injuries. Zebrafish, on the contrary, are able to regenerate multiple organs including amputated fins, lesioned brain, retina, spinal cord as well as the heart. In response to injury, spared zebrafish cardiomyocytes re-enter the cell cycle, proliferate and form new cardiomyocytes robustly, resulting in full morphological and functional recovery. Since zebrafish heart regeneration was first described about a decade ago, this model has significantly improved our knowledge about the underlying mechanisms of natural heart regeneration. Here, we describe different heart injury techniques and review our current knowledge about cellular and molecular mechanisms of regeneration, with a focus on factors regulating cardiomyocyte proliferation.