Fig. 2

Epithelial healing after tooth extraction in a histological study. a Experimental protocol for the in-vivo experiments. Wild-type C57BL/6 N mice received both dexamethasone (Dex) and zoledronate (Zol) administered intravenously for 2 weeks. c-MSCs or d-MSCs were injected into the mice a day after tooth extraction (c-MSC(+) and d-MSC(+)). Control mice received no treatment and MRONJ mice received both Dex and Zol but had no MSC treatment. b MRONJ model mice without treatment and with diseased MSCs had a lack of epithelial lining in the alveolar socket. In contrast, 100 % of the MSC-treated mice showed complete epithelial coverage, which was confirmed by the histological study. Moreover, MRONJ mice had higher IL-2 and IL-6 levels, and lower IL-10 levels than the controls. Inflammatory cytokine levels of the c-MSC(+) model were similar to those of the controls. The lung, kidney, liver, and spleen of the MRONJ model had obvious destruction of the typical structure, invasion of inflammatory cells, and necrosis of components. These inflammatory organ characteristics were recovered by c-MSCs but not d-MSCs. n = 5 × 4 groups. c-MSC control MSC, d days, d-MSC diseased MSC, i.p. intraperitoneal, i.v. intravenous, MRONJ medication-related osteonecrosis of the jaw, MSC mesenchymal stem cell