Curiosity Killed the Cat and Found New Myocytes

Abstract

See related article, pages 1226–1237 Not very long ago when I set up my first research laboratory in the early 1990s, the prevailing wisdom was that new myocyte formation in the mature myocardium was nonexistent or occurred with about the same frequency as an appearance of Halley's comet.1,–,3 Occasional sightings of myocytes undergoing what appeared to be mitotic division4,5 in adult tissue sections were compared to the proverbial “needle in a haystack” and often dismissed as biologically irrelevant in terms of cardiomyocyte replacement or myocardial repair.6 In short, the heart was a postmitotic organ with essentially no capacity for new myocyte formation. If only there were cells that possessed the capability for de novo formation of cardiomyocytes and vasculature, then perhaps we could repair pathological injury in the heart. Researchers tried to force myocytes to divide using molecular maneuvers,7,8 force neonatal myocytes to engraft into mature hearts,9 and even force chimeric marriage between skeletal muscle and the heart in attempts to restore contractile function.10,11 A lot of hearts were broken, but we were not doing a very good job of fixing them. Amazing what a difference a decade can make. After years of searching for the source of new myocyte formation, it turns out that while isolating adult and neonatal myocytes, we had been “throwing the baby out with the bathwater.” In retrospect, it seems so obvious. Precursors for new myocyte …