VEGFR2-dependent Angiogenic Capacity of Pericyte-like Dental Pulp Stem Cells

Dental pulp stem cells (DPSCs) have previously demonstrated potential pericyte-like topography and function. However, the mechanisms regulating their pericyte function are still unknown. In this study, murine DPSC angiogenic and pericyte function were investigated. Tie2-GFP mouse DPSCs were negative for GFP, indicating the absence of endothelial cells in DPSC cultures. Endothelial cells co-cultured with DPSCs formed more mature in vitro tube-like structures as compared with those co-cultured with bone marrow stromal cells (BMSCs). Many DPSCs were located adjacent to vascular tubes, assuming a pericyte location. Subcutaneous DPSC transplants in mice with matrigel (MG) (DPSC-MG) induced more vessel formation than BMSC-MG. Soluble Flt (sFlt), an angiogenic inhibitor that binds VEGF-A, significantly decreased the amount of blood vessels in DPSC-MG, but not in BMSC-MG. sFlt inhibited VEGFR2 and downstream ERK signaling in DPSCs. Similar to sFlt inhibition, VEGFR2 knockdown in DPSCs resulted in down-regulation ...