CXCR4 positive bone mesenchymal stem cells migrate to human endothelial cell stimulated by ox-LDL via SDF-1alpha/CXCR4 signaling axis

Abstract

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-1alpha) is involved in the process of atherogenesis. This study was aimed at investigating whether the SDF-1alpha of human umbilical vein endothelial cells (HUVECs) plays a role in migration of BM-derived CXCR4(+)(receptor for SDF-1alpha) stem cells.

Methods: HUVECs were cultured from human umbilical cords and was treated with ox-LDL. The mRNA and protein expression of SDF-1alpha 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-1alpha. Ox-LDL increased the migratory and adhesion response of CXCR4(+)BMSCs. When the neutralizing SDF-1alpha antibody abrogated the secreted SDF-1alpha, the migration and adhesion response of CXCR4(+)BMSCs markedly decreased.

Conclusions: Our data indicated that the endothelial cells (ECs) stimulated by ox-LDL could increase the BMSCs migratory response via SDF-1alpha/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.