The baby and the bath water: adult cardiac stem cells revisited.

Heart failure (HF), the progressive disorder with >50% mortality 5 years after onset, is due to a deficit in cardiomyocyte number and/or function. Despite remarkable treatment advances, HF remains a major challenge in cardiovascular medicine because, except for heart transplant, none of the available therapy stably restores the deficit in functional cardiomyocytes.

Evidence that soon after birth cardiomyocytes become terminally differentiated and unable to re-enter the cell cycle led to the conclusion that the adult heart was a terminally differentiated organ unable to generate new myocytes, a conclusion reinforced by the rare existence of cardiac neoplasias. This implied that, from cradle to grave, life depended on the cohort of cardiomyocytes present shortly after birth but inexorably decreasing in number by the wear and tear of the uninterrupted heartbeat.

The discovery that tissue-specific adult stem cells are responsible for the cellular homeostasis and regeneration of most adult organs, including the brain, left the heart, despite its indispensability for organism survival, as the only major organ unable to generate new parenchymal cells throughout life. This biological exceptionalism of the heart was finally challenged by demonstration of the slow but continuous appearance of new cardiomyocytes throughout life, followed by the identification, isolation, and characterization of a rare population of myocardial cells with all the expected characteristics of an adult cardiac stem cell. Yet, the exceptionalism of the heart as a non-regenerative organ mostly remains ingrained in the cardiovascular community.