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

Abstract

Objectives 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. Methods Human gingival fibroblasts were cultured with EPC‐conditioned media (EPC‐CM); endothelial growth media (EGM‐2) or DMEM followed by incubation with 10 µM 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 11 weeks. After a week, EPCs or EGM‐2 were injected to the gingiva around the molars. At 3 weeks, bilateral molars were extracted. After 8 weeks, wound healing was assessed, and serum VEGF and blood vessels were quantified. Results 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. Conclusion 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.

Oral fibroblasts rescue osteogenic differentiation of mesenchymal stem cells after exposure to Zoledronic acid in a paracrine effect

“…Moreover, we present an in vitro study, which is very limited. Several in vivo MRONJ models showed preventive and therapeutic effects of MSCs and endothelial progenitor cells conditioned media on MRONJ ( Kikuiri et al, 2010 ; Matsuura et al, 2016 ; Doppelt et al, 2020 ). MSCs, and to much greater extent endothelial progenitor cells, are very difficult to obtain and expand because of their low numbers in blood and bone marrow.…”

Medication‐related osteonecrosis of the jaw: A disease of significant importance for older patients

“…Moreover, recent in vitro studies have provided encouraging data indicating that the addition of endothelial progenitors would prevent the anti‐fibroblastic effect of zolendronic acid and dexamethasone, increasing vascularization and ultimately preventing MRONJ 78 . This has led to several types of tissue engineering approaches combining the use of angiogenic growth factors and/or transplantation of proangiogenic cells, such as endothelial progenitor cells within scaffolds.…”