Regeneration of a heart cell.

Cardiomyocytes, the beating cells in all mammalian hearts, generally are believed to be terminally differentiated cells that do not proliferate after birth. Instead, the growth of a heart from the neonatal to adult stage results primarily from a phenomenon called hypertrophy, during which cardiomyocytes increase their cell size without undergoing cell division. This dogma was recently challenged by two outstanding publications from the Lee [1] and Frisen [2] groups. Using a mouse genetic fate-mapping strategy, the Lee group showed strong evidence that stem or progenitor cells refreshed murine cardiomyocytes after heart injury, but not during up to one year of normal aging [1]. Additionally, taking advantage of the incorporation of carbon-14 produced during the Cold War into DNA, the Frisen group established a way to determine the age of cardiomyocytes. Using this method, they demonstrated that human cardiomyocytes renew themselves, although at a low frequency [2]. These studies have opened a new and exciting avenue for research into cardiac repair mechanisms, such as developing pharmacological agents to stimulate the low level of cardiac repair function of mammalian hearts. However, the development of such agents is hindered by the identities of the cardiac stem or progenitor cells able to refresh the injured or aged cardiomyocytes remaining unknown. As an alternative strategy, one could isolate these cardiac stem/progenitor cells from heart tissues or embryonic stem (ES) cells and use them for cell-based therapies for cardiomyocyte replacement. But before a fruitful clinical application of cardiac stem cell/progenitor cells can be established, there are a few roadblocks we need to clear up.