Exploring the source of human cardiac regeneration

Abstract

The human heart is known to have limited regenerative capacity, and the source of new cardiomyocytes remains enigmatic. The existence of stem cells in the adult human heart has been a topic of debate. Recently, a potential stem cell niche in the atrioventricular junction (AVj) of rats was identified. This region was further explored in human hearts, showing expression of cardiac stem cell related markers in the left AVj at the base of the mitral valve. In study I, the right AVj was investigated with immunohistochemistry (IHC) and RNA sequencing. Stem cell markers were expressed in the fibrous region and at the edge of the myocardium, decreasing with distance from the AVj. In study II, an alternative regenerative mechanism, cardiomyocyte dedifferentiation, was investigated through IHC on cardiac tissue from organ donors who have had cardiac arrest. A subpopulation of cardiomyocytes in the left ventricle (LV) reduced expression of cardiac troponin T, and upregulated stem cell markers, suggesting dedifferentiation. Study III utilized proteomics, supported with RNA sequencing and IHC, to explore the left AVj. Proteins involved with cardiac development and stem cell niches were expressed. In conclusion, the results of these studies suggest the AVj as a potential niche and source of cardiac progenitor cells. Additionally, dedifferentiation of cardiomyocytes might play a role in cardiac regeneration following injury, such as cardiac arrest.