Abstract P108: Direct Evidence of Postnatal Cardiomyocyte Generation in Murine Models of Aging and Cardiac Injury
The dogma of the adult mammalian heart as a post-mitotic organ has recently come under question. Radiolabeled isotope studies have demonstrated that the human heart exhibits a low rate of renewal of cardiomyocytes throughout one’s lifespan. Furthermore, a recent study has elegantly shown that a neonatal mouse can regenerate its ventricle if the chamber is resected within the first week of birth. However, a number of questions remain unanswered about the nature of the cell type that gives rise to cardiomyocytes postnatally. The field has yet to clonally address whether cardiomyocytes divide symmetrically upon birth, or if a resident progenitor differentiates into cardiomyocytes. Rather than rely on proxies for cell division (e.g. BrdU incorporation studies), we use genetic mouse models in which cell division results in asymmetric, indelible labeling of the daughter cells (“Mosaic analysis of double markers” (MADM)) and a stochastic multi-color Cre reporter in the Rosa26 locus akin to the “Brainbow” mouse to investigate postnatal cell division clonally in order to identify which cell type(s) generate cardiomyocytes. Our studies have demonstrated limited symmetric division of cardiomyocytes during normal aging up to six weeks, with a significantly high rate of cardiomyocyte division during the first postnatal week. While we provide evidence for limited cell division in the peri-infarct region of a myocardial infarction model in the 24 hours after the infarct, the extent of cell division and proliferation over a longer time frame after the infarct remains to be explored.
- © 2011 by American Heart Association, Inc.