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Different vertebrate species have different cardiac regeneration rates: high in teleost fish, moderate in urodele amphibians, and almost negligible in mammals. Regeneration may occur through stem and progenitor cell differentiation or via dedifferentiation with residual cardiomyocytes reentering the cell cycle. In this review, we will examine the ability of zebrafish and newts to respond to cardiac damage with de novo cardiogenesis, whereas rodents and humans respond with a marked fibrogenic response and virtually no cardiomyocyte regeneration. Concerted strategies are needed to overcome this evolutionarily imposed barrier and optimize cardiac regeneration in mammals.

From fish to amphibians to mammals: in search of novel strategies to optimize cardiac regeneration