This review paper explores cutting-edge strategies for adult mammalian heart regeneration, with a particular focus on the paradigm shift from traditional stem cell transplantation toward the study of paracrine factors such as exosomes. The authors propose an innovative model of cardiogenesis, suggesting that cardiac stem cells (CSCs) do not directly differentiate into mature cardiomyocytes. Instead, they form intracellular developmental structures known as cell-in-cell structures (CICSs) within mature cardiomyocytes, which subsequently release highly proliferative transit-amplifying cells (TACs) that contribute to tissue repair.

The paper further examines the dual role of hypoxic environments in triggering regenerative mechanisms and compares two distinct therapeutic approaches: activating endogenous repair pathways versus delivering ...