Endothelial progenitors increase vascularization and improve fibroblasts function that prevent medication-related osteonecrosis of the jaw.

Abstract

In a previous rat model, MRONJ occurrence was 50%. Our aim was to investigate the potential of endothelial progenitor cells (EPCs) to improve fibroblasts function and prevent MRONJ. Human gingival fibroblasts were cultured with EPC-conditioned media (EPC-CM); endothelial growth media (EGM-2) or DMEM followed by incubation with 10µM zoledronic (ZOL) and dexamethasone (DEX). Cell proliferation and migration were assessed by XTT and scratch wound healing assays. In vivo, ten Lewis rats were treated weekly with ZOL and DEX for 11weeks. After a week, EPCs or EGM-2 were injected to the gingiva around the molars. At 3weeks, bilateral molars were extracted. After 8weeks, wound healing was assessed, and serum VEGF and blood vessels were quantified. ZOL/DEX significantly reduced fibroblasts proliferation and wound healing. Treatment with EPC-CM before ZOL/DEX improved cell proliferation, and scratch healing (p=.007, p=.023).In vivo, local EPC injection before tooth extraction increased serum VEGF (p=.01) and soft tissue vascularization (p=.05). Normal healing was similar (80%) in EPCs and EGM-2 groups. EPC rescued fibroblasts from the cytotoxic effect of ZOL/DEX and elevated serum VEGF and vessel density that might reduce MRONJ occurrence to 20% compared to 50% in a similar model.