Human dental pulp stem cells-derived small extracellular vesicles prevent osteoradionecrosis of the jaw in a rat model.

Abstract

Radiotherapy (RT) is an important standard treatment for head and neck cancer. On the other hand, osteoradionecrosis of the jaw (ORNJ), a side effect of RT, is intractable and has been a long-standing problem that needs to be overcome. Cellular senescence has been linked to the development of ORNJ; however, strategies for preventing and treating this disease have not been established. This study aimed to evaluate the effects of human dental pulp stem cell-derived small extracellular vesicles (hDPSC-sEV) on ORNJ. The effects of hDPSC-sEV treatment on rat bone marrow cells (rBMC) were examined in vitro. In addition, hDPSC-sEV were administered intravenously to a rat ORNJ model, and the extraction socket was examined radiologically and histologically. In vitro, rBMC treated with hDPSC-sEV immediately after irradiation showed downregulated expression of senescence-related genes. In vivo, the extraction sockets of the ORNJ models treated with hDPSC-sEV showed more new bone and greater coverage with gingiva relative to those observed in the comparison groups. This study suggests that hDPSC-sEV may inhibit ORNJ development. One possible mechanism is that hDPSC-sEV inhibit radiation-induced cellular senescence.