Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Accelerate Diabetic Rat Wound Healing by Inhibiting Pyroptosis through the NLRP3/Caspase-1/GSDMD Pathway
Yue Wu, Hongjin Wang, Miao Yu, Jun Liu, Yuanyuan Jin, Hui CaiIntroduction:
Diabetic wounds are a type of chronic wound characterized by delayed and difficult healing. In recent years, the use of bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exo) in wound treatment has shown promising progress. This research aims to investigate whether BMSC-Exo can promote the healing of diabetic wounds and to explore the underlying mechanisms
Methods:
1. Exosome extraction and identification; 2. Animal experiments: 54 male SD rats were randomly divided into 3 groups: Normal control (Control) group, diabetes model + normal saline (DM+NS) group, and diabetes model + exosome (DM+Exo) group. After successful modeling of diabetes, 2 cm × 2 cm wounds were created on the backs of rats in each group. Normal saline was injected into the wounds of the control group and DM+NS group, and exosomes were injected into the wounds of the DM+Exo group. The wound-healing rate in each group was measured, and the levels of NLRP3, IL-18, IL-1β, caspase-1, and GSDMD protein were assessed by Western Blot. 3. Cell experiment: Fibroblasts were divided into 3 groups: fibroblasts (Control) group, fibroblasts + hyperglycemia (Hy) group, and fibroblasts + hyperglycemia + exosomes (Hy+Exo) group. Cells in each group were detected by CCK-8, Annexin V/PI staining, and scratch assay. The levels of NLRP3, IL-18, IL-1β, caspase-1, and GSDMD protein were detected by Western Blot in each group.
Results:
The findings demonstrated that BMSC-Exo significantly enhanced wound healing in diabetic rats and promoted the proliferation and migration of fibroblasts under high-glucose conditions. BMSC-derived exosomes enhanced the wound healing rate by an average of 21.3% in diabetic rat models. Pyroptosis was markedly increased in the wounds of diabetic rats and in fibroblasts exposed to high glucose; however, BMSC-Exo significantly inhibited pyroptosis in both contexts
Discussion:
The poor healing of diabetic wounds is closely associated with hyperglycemiainduced pyroptosis and chronic inflammation; pyroptosis mediated by the NLRP3/caspase1/GSDMD pathway exacerbates inflammation and inhibits fibroblast function. This study is the first to confirm that BMSC-Exo can target this pathway to inhibit pyroptosis, thereby promoting wound healing and expanding the therapeutic mechanism of MSC-derived exosomes. However, the key functional molecules in BMSC-Exo remain unclear, and their long-term efficacy and clinical translation require further verification
Conclusion:
These results suggest that BMSC-Exo promotes wound healing in diabetic rats by inhibiting cell pyr