Evidence for Minimal Cardiogenic Potential of Sca-1 Positive Cells in the Adult Mouse Heart

Abstract

Despite modern pharmacotherapy, heart failure remains a major medical burden. The heart has a limited regenerative capacity, and bolstering regeneration might represent new therapeutic approaches for heart failure patients. Various progenitor cells have been proposed to have cardiomyogenic properties, but this evidence is based mostly on cell culture and transplantation studies. One population of interest is characterized by the expression of Stem Cell Antigen-1 (Sca-1). Here we tested the hypothesis that Sca-1+ cells are endogenous progenitors for cardiomyocytes. We evaluated the innate cardiogenic potential of Sca-1 positive cells in vivo by generating a novel mouse model to genetic lineage-trace the fate of Sca-1+ cells. This was accomplished by introducing a tamoxifen-inducible Cre-recombinase into the Sca-1 locus (Sca-1mCm/+). Crossing this mouse line to a Cre dependent tdTomato reporter line allowed for genetic lineage-tracing of endogenous Sca-1+ cells (Sca-1mCmtdTomato). We validated the genetic lineage tracing mouse model in bone marrow and heart. Unlike previous publications suggesting significant cardiogenic potential, we found that less than 0.1% of cardiomyocytes were derived from Sca-1+ cells in the adult heart under homeostatic conditions and there was no significant change in contribution to cardiomyoctyes six months after myocardial infarction. Our results show that Sca-1+ cells in the adult heart have minimal cardiogenic potential under homeostatic conditions or in response to myocardial infarction.