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Heart disease is the leading cause of mortality worldwide. Due to the limited proliferation rate of mature cardiomyocytes, adult mammalian hearts are unable to regenerate damaged cardiac muscle following injury. Instead, injured area is replaced by fibrotic scar tissue, which may lead to irreversible cardiac remodeling and organ failure. In contrast, adult zebrafish and neonatal mammalian possess the capacity for heart regeneration and have been widely used as experimental models. Recent studies have shown that multiple types of cells within the heart can respond to injury with the activation of distinct signaling pathways. Determining the specific contributions of each cell type is essential for our understanding of the regeneration network organization throughout the heart. In this review, we provide an overview of the distinct functions and coordinated cell behaviors of several major cell types including cardiomyocytes, endocardial cells, epicardial cells, fibroblasts, and immune cells. The topic focuses on their specific responses and cellular plasticity after injury, and potential therapeutic applications.

Cardiac cell type-specific responses to injury and contributions to heart regeneration