IL-1β-stimulated bone mesenchymal stem cell-derived exosomes promote cutaneous wound healing by inhibiting...

Cutaneous wound healing is a complex process of tissue repair and remodeling that includes inflammation, proliferation, and regeneration. Mesenchymal stem cell (MSCs) therapy has emerged as a widely studied therapeutic approach, demonstrating promising therapeutic potential. The purpose of this work is to examine the function and mechanism of exosomes produced from bone marrow mesenchymal stromal cells (BMSCs) pretreatment with IL-1β in the healing of skin injuries. Exosomes were extracted from both untreated BMSCs and those treated with IL-1β. HUVEC proliferation, migration, angiogenesis, and apoptosis were assessed through CCK-8, Transwell, tube formation, qPCR, western blot, and flow cytometry. Wound healing in mice was evaluated using H&E staining, Masson's staining, and immunofluorescence. IL-1β-BMSC-exos significantly enhance the proliferation, migration, and angiogenesis of HUVECs. LPS treatment induces the expression of NLRP3 and SIRT6 in HUVECs and the acetylation of NLRP3, but these effects are mitigated by treatment with IL-1β-BMSC-exos. Knockdown of SIRT6 reverses the pro-angiogenic and anti-inflammatory effects of IL-1β-BMSC-exos by inhibiting NLRP3-mediated inflammation. Furthermore, IL-1β-BMSC-exos reduce skin wound area, increase collagen deposition, promote neovascularization, and accelerate wound healing in a mouse model of skin injury. IL-1β-BMSC-exos have been shown to effectively promote cutaneous wound healing, primarily through the modulation of the SIRT6/NLRP3 signaling pathway, thereby accelerating the repair process of skin trauma. This suggests that IL-1β-BMSC-exos hold therapeutic potential as a future treatment strategy for cutaneous wound healing.