The Migration And Differentiation Of CXCR4 Positive Bone Mesenchymal Stem Cells And The Capable Of Neovascularization

Background:Bone mesenchymal stem cells (BMSCs) are attractive candidates for cell based therapies to cardiovascular disease such as infarction and atherosclerosis; however, the mechanisms responsible for stem cell chemotaxis and homing remain unknown. Chemokine stromal cell-derived factor 1 (SDF-1a) is involved in the process of atherogenesis. This study was aimed at investigating whether the SDF-1a of human umbilical vein endothelial cells (HUVECs) play a role in migration of BM-derived CXCR4+(receptor for SDF-la) stem cells.Methods:HUVECs were isolated and cultured from human umbilical cords and were treated with ox-LDL. The mRNA and protein expression of SDF-la was detected in HUVECs. CXCR4+BMSCs from bone marrow were isolated and were tested by migration and adhesion assays.Results:It was found that ox-LDL induced HUVECs to increase the mRNA and protein expression of SDF-1a. In addition, ox-LDL induced HUVECs to increase the expression of hypoxia-inducible factor-1 (HIF-1a). Ox-LDL enhanced the migratory and adhesion response of CXCR4+BMSCs. When the neutralizing SDF-la antibody abrogated the secreted SDF-la, the migration and adhesion response of CXCR4+BMSCs markedly was inhibited.Conclusions:Our data indicated that the endothelial cells (ECs) stimulated by ox-LDL could increase the BMSCs migratory response via SDF-la/CXCR4 signaling axis. These findings provide a new paradigm for biological effects of ox-LDL and have implications for novel stem cell therapeutic strategies for atherosclerosis. Background: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 post-infarction myocardial repair. CXCR4+ stem/progenitor cells mobilized to the infarct area and improved the myocardial repair. It is unclear what special characteristics the vascular progenitors of bone marrow origin have. In present study, we aimed to determine whether CXCR4+BMSCs contribute to the angiogenic capacity in vitro and in vivo.Methods: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 (ac-LDL) and the capillary tube formation in Materigel were evaluated. The effect of CXCR4+BMSCs transplantation on neovascularization was investigated in a murine model hindlimb ischemia.Results: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-ac-LDL and form capillary-like tubes in vitro. In vivo the local transfer of CXCR4+BMSCs increased neovascularization in ischemic hindlimb.Conclusion:These results demonstrate that CXCR4+BMSCs differentiate into ECs and contribute to neovascularization in the vascular lesion, which indicate the important therapeutic implications for repair-to-injury and a new cell source for cell-based vascular engineering in the future.