The belief that the heart is a terminally differentiated organ was a very well established notion among the scientific community until the early 2000s, although several authors tried to challenge this dogma over the years. Nonetheless, myocyte turnover was only accepted after the demonstration of the intense proliferation that occurs, in human hearts, acutely after myocardial infarction. The first clues indicating that myocytes could originate from unsuspected cell sources, characterized by migratory and differentiation capabilities, were provided by studying the chimerism of transplanted hearts. Following these studies, several classes of cardiac resident primitive cells endowed with cardiomyogenic potential were discovered. Specifically, murine cells expressing c-Kit, Sca1, Abcg2, Isl1, Tbx18, or Wt1 demonstrated their ability to differentiate into cardiac myocytes. Regarding human hearts, cardiospheres, c-Kit+ cells, multipotent adult stem cells, and possibly epicardial cells can differentiate into cardiac myocytes. However, cardiac stem cell (CSC) biology is at its beginning and critical questions such as the origin of CSCs and the relationships existing between different stem/progenitor cell classes still need to be answered.
