Laboratory for Bone Repair, Rambam Health Care Campus, Haifa, Israel.
The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
Oral Dis. 2020 Oct;26(7):1523-1531. doi: 10.1111/odi.13412. Epub 2020 Jul 13.
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 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.
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.
在先前的大鼠模型中，MRONJ 的发生率为 50%。我们的目的是研究内皮祖细胞（EPCs）是否有潜力改善成纤维细胞功能并预防 MRONJ。
培养人牙龈成纤维细胞，用 EPC 条件培养基（EPC-CM）；内皮生长培养基（EGM-2）或 DMEM 孵育，然后用 10µM唑来膦酸（ZOL）和地塞米松（DEX）处理。通过 XTT 和划痕愈合试验评估细胞增殖和迁移。在体内，10 只 Lewis 大鼠每周接受 ZOL 和 DEX 治疗 11 周。治疗一周后，将 EPCs 或 EGM-2 注射到磨牙周围的牙龈中。3 周后，双侧磨牙被拔出。8 周后，评估伤口愈合情况，并定量血清 VEGF 和血管。
ZOL/DEX 显著降低了成纤维细胞的增殖和伤口愈合。在 ZOL/DEX 之前用 EPC-CM 处理可改善细胞增殖和划痕愈合（p=0.007，p=0.023）。在体内，拔牙前局部注射 EPC 可增加血清 VEGF（p=0.01）和软组织血管化（p=0.05）。EPC 组和 EGM-2 组的正常愈合率相似（80%）。
EPC 可使成纤维细胞免受 ZOL/DEX 的细胞毒性作用，提高血清 VEGF 和血管密度，与类似模型中 50%的发生率相比，MRONJ 的发生率可能降低至 20%。
