Abstract 218: Cardiac Side Population Cells Give Rise to Cardiomyocytes in the Adult Heart

Abstract

Therapies that enhance cardiac regeneration have the potential to improve heart failure outcomes. One strategy to enhance cardiac regeneration is by activating endogenous cardiac progenitor cells. Cardiac side population cells (cSPCs) are proposed progenitor cells that reside in the heart; however, their putative progenitor cell properties are based on cell culture data and transplantation studies performed with isolated cSPCs. To determine the endogenous regenerative potential of cSPCs in vivo , we generated a mouse model that harbors an Abcg2-driven, tamoxifen-inducible Cre recombinase and crossed it to a GFP reporter mice. One month after tamoxifen treatment, we obtained efficient GFP-labeling of side population cells with 47.0 ± 11.05% of bone marrow side population cells and 75.8 ± 10.87% of cSPCs. Importantly, during a one-month chase period, we observed a three-fold increase in GFP-labeled cardiomyocytes when compared to a 1-week chase period. We quantified the extent of GFP-labeling of cardiomyocytes using adult cardiomyocyte isolation, where we measured 0.8% GFP labeled cardiomyocytes after a one-month chase period. We also observed labeling of many other cell types in the heart, such as endothelial cells, smooth muscle cells, and pericytes. We are currently testing to what extent cardiac injury enhances cSPC derived cardiomyocyte formation. Using our mouse model that efficiently labels side population cells in vivo , we demonstrated that cSPCs contribute cardiomyocytes in the adult heart in vivo .