Stem cell populations in the heart and the role of Isl1 positive cells

Cardiac progenitor cells are multipotent stem cells isolated from both embryonic and adult hearts in several species and are able to differentiate at least into smooth muscle cells, endothelial cells and cardiomyocytes. The embryonic origin of these cells has not yet been demonstrated, but it has been suggested that these cells may derive from the first and secondary heart fields and from the neural crest. In the last decade, two different popula-tions of cardiac progenitor or stem cells have been identified and isolated, i.e., the Islet1 positive (Isl1+) and c-Kit positive (c-Kit+)/Stem Cell Antigen-1 positive (Sca-1+) cells. Until 2012, these two populations have been considered two separate entities with dif-ferent roles and a different origin, but new evi-dence now suggests a connection between the two populations and that the two populations may represent two subpopulations of a unique pool of cardiac stem cells, derived from a com-mon immature primitive cell. To find a com-mon consensus on this concept is very impor-tant in furthering the application of stem cells to cardiac tissue engineering. Islet1 positive cells duringheart development At the end of 2003, the research group of Prof. Evans, using a mouse mutant for the LIM homeodomain transcription factor (Islet1, Isl1), demonstrated that an Isl1 positive (Isl1+) population is localised in the secon-dary heart field (SHF), contributing to the out-flow tract, right ventricle, atria and (to a small extent) the left ventricle.1 Isl1 is considered a marker of SHF cells that contribute to the venous and arterial poles of the cardiac tube, while the other cells from the SHF contribute only to the arterial pole.2 The SHF or anterior heat field (AHF) was identified as a splanchnic mesoderm underlying the caudal pharynx, which provides myocardium to the outflow tract during tube looping.3,4 In 2005, the same research group also identified Isl1+/c-Kit negative (c-Kit-)/Stem Cell Antigen-1 negative (Sca-1-) progenitors in the postnatal heart, demonstrating that these cells persist after birth and that these organ-specific progenitor cells may be isolated, purified, expanded and differentiated into mature cardiac myocytes for future cardiac applications