Vascular endothelial growth factor/platelet-derived growth factor receptor pathway is involved in bone marrow mesenchymal stem cell differentiation and directional migration toward gliomas

BACKGROUND: Vascular endothelial growth factor (VEGF) induces bone marrow-derived mesenchymal stem cell (BMSC) differentiation into vascular endothelial-like cells and promotes BMSC migration toward gliomas. However, the molecular mechanisms by which VEGF induces BMSC differentiation and migration remain poorly understood. OBJECTIVE: To investigate the role of platelet-derived growth factor (PDGF) receptor (PDGFR) in BMSC differentiation and migration induced by VEGF. DESIGN, TIME AND SETTING: A parallel, controlled, in vitro experiment was performed at the Molecular Neurobiology & Neural Regeneration and Repairing Laboratory, Anhui Provincial Hospital of Anhui Medical University, China from June 2008 to March 2009. MATERIALS: U87 glioma cells were purchased from Shanghai Institutes for Biological Sciences; mouse anti-human PDGFR and VEGF receptor (VEGFR) monoclonal antibodies were purchased from Peprotech, USA. METHODS: Isolated BMSCs were precultured with neutralizing antibody for VEGFR-1, VEGFR-2, PDGFR-alpha, and PDGFR-beta to block biological activity of related receptors, followed by induced differentiation with 50 mu g/L VEGF. BMSCs induced with 50 mu g/L VEGF alone served as the VEGF-induced group. The control group remained untreated. MAIN OUTCOME MEASURES: Cell surface markers were identified by flow cytometry; BMSC surface cytokine receptor expression was detected by reverse transcription-polymerase chain reaction; the Transwell model was used to observe cell migration. RESULTS: After blocking the PDGFR, VEGF did not induce BMSC cell surface marker CD-31 or von Willebrand factor (vWF) expression. However, inhibition with VEGF receptor blocking agents, VEGF induced BMSCs to express CD-31 and vWF. Following inhibition of the PDGFR, the number of cells migrating through the polycarbonate membrane Transwell chamber was decreased, as well as the number of BMSCs migrating to glioma cells. However, through the use of VEGF receptor blocking agents, the number of migrating cells remained unchanged. VEGF preculture increased the number of BMSCs migrating to gliomas. CONCLUSION: VEGF interacts with PDGFRs on the BMSC surface to attract BMSC directional migration and induce BMSC differentiation. The VEGF/PDGFR pathway participates in BMSC directional migration to glioma. VEGF pretreatment increased efficiency of BMSC migration to glioma.