Oxidized-low density lipoprotein (ox-LDL) is believed to contribute to atherogenesis in part by being taken up into smooth muscle cells (SMC) via specific scavenger receptors; however, it is not clear whether ox-LDL receptor(s) are expressed in bone marrow-derived smooth muscle-like cells (SMLCs) and whether they play a role in the process of SMLC development. Therefore, we examined the ox-LDL-induced transdifferentiation of SMLCs that is mediated by lectin-like ox-LDL receptor-1 (LOX-1). Smooth muscle progenitor cells (SMPCs) from bone marrow mesenchymal stem cells (BMSCs) were isolated using a tissue-specific promoter sorting method with a mouse SM22_ promoter (_480 bp)/green fluorescent protein recombinant plasmid. The SMPCs were myocardin+CD105+KDR+CD45(-)CD34(-), but did not express SMC-specific markers alpha-smooth muscle actin (alpha-SMA), SM22, smooth muscle myosin heavy chain (SM-MHC) and smoothelin. After long-term culture with platelet-derived growth factor-BB (PDGF-BB), SMPCs expressed alpha-SMA, SM22 and SM-MHC and differentiated into SMLCs. When SMLCs were incubated with different concentrations of ox-LDL, LOX-1 expression on the surface of SMLCs gradually increased with the increase of the ox-LDL concentration, but myocardin and SMC-specific marker genes decreased, accordingly. Furthermore, receptor-mediated endocytosis was enhanced and lipid droplets accumulated in the cytoplasm of SMLCs. A subpopulation of myocardin+CD105+KDR+CD45(-)CD34(-) SMPCs exist in BMSCs that can differentiate into SMLCs under induction with PDGF-BB. Moreover, LOX-1 contributes to the ox-LDL-induced transdifferentiation of bone marrow-derived SMLCs into foam-like cells.

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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.