Two decades of heart regeneration research: Cardiomyocyte proliferation and beyond

Abstract

Interest in vertebrate cardiac regeneration has exploded over the past two decades since the discovery that adult zebrafish are capable of complete heart regeneration, contrasting the limited regenerative potential typically observed in adult mammalian hearts. Undercovering the mechanisms that both support and limit cardiac regeneration across the animal kingdom may provide unique insights in how we may unlock this capacity in adult humans. In this review, we discuss key discoveries in the heart regeneration field over the last 20 years. Initially, seminal findings revealed that pre‐existing cardiomyocytes are the major source of regenerated cardiac muscle, drawing interest into the intrinsic mechanisms regulating cardiomyocyte proliferation. Moreover, recent studies have identified the importance of intercellular interactions and physiological adaptations, which highlight the vast complexity of the cardiac regenerative process. Finally, we compare strategies that have been tested to increase the regenerative capacity of the adult mammalian heart.This article is categorized under: Cardiovascular Diseases > Stem Cells and Development

Quantitative Three-dimensional Label-free Digital Holographic Imaging of Cardiomyocyte Size, Ploidy, and Cell Division

“…During our digital holographic imaging experiments, cardiomyocyte nuclei could be identified as round structures with approximately 10 μm diameters that have less overall vertical thickness. Polyploidization is thought to limit the proliferative potential of cardiomyocytes and is considered a major barrier to cardiac regeneration (Derks & Bergmann, 2020; Huang et al, 2023; Mehdipour et al, 2023). Therefore, we next determined if mononucleated and binucleated cardiomyocytes exhibited different proliferative responses to CHIR99021 stimulation.…”

“…The copyright holder for this preprint this version posted November 4, 2023. ; https://doi.org/10.1101/2023.11.02.565407 doi: bioRxiv preprint regeneration (Derks & Bergmann, 2020;Huang et al, 2023;Mehdipour et al, 2023). Therefore, we next determined if mononucleated and binucleated cardiomyocytes exhibited different proliferative responses to CHIR99021 stimulation.…”