Exosomes Derived from Adipose Tissue-Derived Mesenchymal Stromal Cells Prevent Medication-Related Osteonecrosis of the Jaw through IL-1RA.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• 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)

Medication-related osteonecrosis of the jaw (MRONJ) is a severe disease with unclear pathogenesis. Adipose tissue-derived mesenchymal stromal cells (MSC(AT)s) serve as a special source for cell therapy. Herein, we explored whether exosomes (Exo) derived from MSC(AT)s promote primary gingival wound healing and prevent MRONJ. An MRONJ mice model was constructed using zoledronate (Zol) administration and tooth extraction. Exosomes were collected from the conditioned medium (CM) of MSC(AT)s (MSC(AT)s-Exo) and locally administered into the tooth sockets. Interleukin-1 receptor antagonist (IL-1RA)-siRNA was used to knock down the expression of IL-1RA in MSC(AT)s-Exo. Clinical observations, micro-computed tomography (microCT), and histological analysis were used to evaluate the therapeutic effects in vivo. In addition, the effect of exosomes on the biological behavior of human gingival fibroblasts (HGFs) was evaluated in vitro. MSC(AT)s-Exo accelerated primary gingival wound healing and bone regeneration in tooth sockets and prevented MRONJ. Moreover, MSC(AT)s-Exo increased IL-1RA expression and decreased interleukin-1 beta (IL-1β) and tumor necrosis factor-α (TNF-α) expression in the gingival tissue. The sequent rescue assay showed that the effects of preventing MRONJ in vivo and improving the migration and collagen synthesis abilities of zoledronate-affected HGFs in vitro were parti

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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