Differentiation potential of cardiac stem and progenitor cells in a model of heterotopic heart transplantation

Cardiac stem cells were identified in mammalian hearts and they were found to regenerate cardiomyocytes and vessels when injected into an infarcted heart. We used the model of heterotopic heart transplantation to investigate spontaneous potential of cardiac stem and progenitor cells to differentiate properly after tissue damage and remodeling. In a previous study, in which hearts from normal rat donors were heterotopically transplanted into GFP+ transgenic rat hosts, we found abundant extracardiac GFP+ cells that did not contribute to de novo cardiogenesis, but generated rare hybrid cardiomyocytes by cell fusion with resident cardiac cells. In the same transplants we recently identified a robust population of GFP− cells expressing markers of stem and mesenchymal cells. Markers of cardiac commitment and neural stem cells identified different populations of cell progenitors. The overall number of these cells increased 5-fold in heart transplants as compared to normal hearts. The majority of these cells did not progress towards maturation, however cardiomyocytes expressing phosphohistone- H3 were occasionally found. A major issue is whether cardiac stem cells can detach from a damaged heart, circulate and from the bloodstream home again into the heart. To address this question the heart of GFP+ transgenic rats was transplanted into a normal host, which had been previously treated with isoproterenol, to induce damage in the native heart. Native hearts, retrieved 15 days after surgery, did not show any significant engraftment by cardiac stem cells mobilized from the heart transplant.