Cardiac regeneration in vivo: Mending the heart from within?

• There is no consensus in the magnitude of adult cardiomyogenesis in higher mammals.
• 14C dating established the continual generation of myocytes in the human heart.
• Numerous candidates for cardiac stem cells (CSCs) have been proposed.
• Fate-mapping strategies are needed to establish regenerative cell sources in the heart.

A growing body of evidence has shown that the heart is not terminally differentiated but continues to renew its cardiomyocytes even after the neonatal period. This new view of the heart increases hope for changing the strategy for treating cardiac injuries toward regenerative approaches. However, the magnitude and clinical significance of this process in homeostasis and disease and the underlying cellular and molecular mechanisms have been heavily debated. Numerous candidates for so-called cardiac stem cells (CSCs) have been proposed, but the different characteristics of these candidates make it difficult to identify the inherent source of regeneration. In this review, we revisit the field of cardiac stem cells and endogenous regeneration to elaborate how these fields may contribute to future regenerative strategies.

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