Exosomes from Adipose-Derived Mesenchymal Stromal Cells Prevent Medication-Related Osteonecrosis of the Jaw by Inhibiting Macrophage M1 Polarization and Pyroptosis.

Early human evidence such as case series or small samples is exploring possible benefits.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Purpose Exosomes from mesenchymal stromal cells (MSCs) can prevent the development of medication-related osteonecrosis of the jaw (MRONJ) by promoting tooth socket wound healing; however, the exact mechanism remains to be clarified. In this study, our aim was to explore the mechanisms of exosomes derived from adipose-derived mesenchymal stromal cells (ADSCs) in preventing MRONJ by focusing on macrophage M1 polarization and pyroptosis. Methods The MRONJ model was established by the administration of zoledronate and tooth extraction. Exosomes isolated from the supernatant of ADSCs were mixed with hydrogel and locally injected into the extraction site after tooth extraction. Stereoscope observations, micro computed tomography (microCT), and histological analysis were used to assess tooth socket wound healing. Results The results showed that exosomes could effectively avoid MRONJ via accelerating gingival wound healing and tooth socket bone regeneration. Mechanistically, zoledronate triggered the NF-κB signaling pathway and promoted p65 transferring into the nucleus in macrophages, resulting in macrophage M1 polarization and pyroptosis-mediated tissue inflammation, while exosomes could reduce macrophage pyroptosis and pro-inflammation cytokines release by suppressing the NF-κB/NLRP3/IL-1β axis. Additionally, IL-1RA derived from exosomes plays a key role in preventing MRONJ. Pyropto

Evidence level

Early human evidence such as case series or small samples is exploring possible benefits.

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