CXCR4+ progenitors derived from bone mesenchymal stem cells differentiate into endothelial cells capable of vascular repair after arterial injury

Abstract

Recent findings indicate that bone marrow mesenchymal stem cells (BMSCs) participate in the process of neovascularization in response to repair to injury and are involved in postinfarction myocardial repair. It is unclear what special characteristics the vascular progenitors of bone marrow origin has. CXCR4(+) stem/progenitor cells mobilized to the infarct area and improved the myocardial repair. In present study, we aimed to determine whether CXCR4(+)BMSCs contribute to the angiogenic capacity in vitro and in vivo. CXCR4(+)BMSCs were separated by using paramagnetic microbeads and cultured. RT-PCR and FACS analysis confirmed the gene expression phenotype. The uptake of acetylated low density lipoprotein (acLDL) and the tube formation evaluated the function of CXCR4(+)BMSCs. The effect of CXCR4(+)BMSCs transplantation on neovascularization was investigated in a murine model hindlimb ischemia. After induced by VEGF, CXCR4(+)BMSCs expressed the endothelial cells (ECs) phenotype. The expression of EC markers, PECAM-1, and von Willebrand factor (vWF) increased significantly at both the mRNA and protein levels. In addition, CXCR4(+)BMSCs enhanced the uptakes of Dil-acLDL and form capillary-like tubes in vitro. In vivo the local transfer of CXCR4(+)BMSCs increased neovascularization in ischemic hindlimb. These results demonstrate that CXCR4(+)BMSCs differentiate into ECs and contribute to neovascularization in the vascular lesion,, which indicate the important therapeutic implications for cardiovascular diseases and a new cell source for cell-based vascular engineering and repair in the future.