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Keywords:

  • migration;
  • myocardial ischemia;
  • SDF-1α/CXCR4;
  • side-population cells;
  • stem cells

To cite this article: Liang SX, Khachigian LM, Ahmadi Z, Yang M, Liu S, Chong BH. In vitro and in vivo proliferation, differentiation and migration of cardiac endothelial progenitor cells (SCA1+/CD31+ side-population cells). J Thromb Haemost 2011; 9: 1628–37.

Summary. 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.