‘Dormant stem/progenitor cells lurking in the adult heart’


Over the last twenty years, cardiac regeneration has progressed from an interesting but marginal area of cardiovascular biology to the vanguard of genetic, molecular and cellular biology, efficiently bridging findings to clinical trials. Great inspiration comes from the robust regeneration seen in zebrafish and newborn mice and from highly sensitive methods that detect very low levels of regeneration. Thus, eliciting an effective reparative and regenerative response in the, otherwise largely dormant, adult heart has become plausible. In particular, major advances have been achieved with cardiac stem/progenitor cells, which can be harvested from adult heart tissue, expanded in vitro and delivered to the myocardium as a therapeutic product. Indeed, encouraging results from clinical trials demonstrate feasibility and safety. Nevertheless, to enhance the effectiveness of cell therapy on cardiac function, improvement of cell retention and cardiomyocyte differentiation is necessary, as well as a better understanding of the beneficial secretory paracrine effects. A valid alternative to cell therapy is to target the cardiac stem/progenitor cells in situ, in order to elicit directly their regenerative capacity from within the heart. However, to achieve these goals, we need to fill the gap of knowledge of the target cells. Indeed, in pre-clinical studies several types of cardiac progenitors were described although their (inter)-relationships remains unclear. Additionally, in clinical trials the most widely used product is an intentionally, but incompletely characterised, heterogeneous pool of cells. Here, I will discuss our single-cell level approaches to define and understand cardiac progenitors and attempt to address three crucial issues: define the heterogeneity of well-established adult cardiac Sca1+ progenitors; pinpoint the subset of cardiac progenitor cells with clonal growth; identify the combination of distinguishing markers that best demarcates a robust cardiogenic potential of heart derived progenitors. Taken together, the data lead to the identification of cardiac quiescent progenitor-like cells resembling a forme fruste of cardiac mesoderm.