In vitro and in vivo proliferation, differentiation and migration of cardiac endothelial progenitor cells (SCA1 +/CD31 + side-population cells)

Abstract

Background: Side-population (SP) cells are a select population identified by a capacity to efflux Hoechst dye and are enriched for stem/progenitor cell activity. Previous studies suggested that cardiac SP (CSP) cells could be divided into SCA1 +/CD31 - and SCA1 +/CD31 + CSP cells. SCA1 +/CD31 - CSP cells have been shown to be cardiac stem/progenitor cells. However, SCA1 +/CD31 + CSP cells have not been fully characterized. Objective: The aim of the present study was to characterize SCA1 +/CD31 + CSP cells in the adult mouse heart, and investigate their abilities to proliferate, differentiate, vascularize and migrate in vitro and in vivo. Results: Using fluorescence-activated cell sorting (FACS), RT-PCR, and assays of cell proliferation, differentiation and migration, and a murine model of myocardial infarction (MI), we showed that SCA1 +/CD31 + CSP cells express stem cell and endothelial-specific genes, and reside in the blood vessels. These cells were able to proliferate, differentiate, migrate and vascularize in vitro and in vivo. After MI, SDF-1α and CXCR4 were up-regulated in the damaged myocardium and on SCA1 +/CD31 + CSP cells, respectively. Our results further showed that SDF-1α induced migration of these cells in vitro. Importantly, we found that SCA1 +/CD31 + CSP cells could migrate into the ischemic region from the non-ischemic area within the myocardium and form a vascular tube-like structure after MI. Conclusions: Based on the gene expression profile, localization of SCA1 +/CD31 + CSP cells, and their ability to proliferate, differentiate, migrate and vascularize in vitro and in vivo, we postulate that SCA1 +/CD31 + CSP cells may represent endothelial progenitor cells in the mouse heart. © 2011 International Society on Thrombosis and Haemostasis.