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 of vegfa,vegf receptors,and ephrinb2 and decreased angiogenic induction of dpscs in vivo. therefore,the capacity of dpscs to induce angiogenesis is vegfr2-dependent. dpscs enhance angiogenesis by secreting vegf ligands and associating with vessels resembling pericyte-like cells. this study provides first insights into the mechanism(s) of dpsc angiogenic induction and their function as pericytes,crucial aspects for dpsc use in tissue regeneration. © international & american associations for dental research.