ADMSC-derived exosomes promote diabetic wound healing by inhibiting neutrophil extracellular traps formation through delivering miR-92a-1-5p.

Adipose-derived mesenchymal stem cell-derived exosomes (ADMSC-ex) have demonstrated remarkable efficacy in promoting diabetic wound healing. However, the underlying mechanisms remain largely elusive. In this study, we showed the healing process of skin wounds in diabetic rats was notably delayed, but this delay was mitigated by the administration of ADMSCs-ex. Neutrophil extracellular traps (NETs) formation was significantly upregulated in the skin wounds from the diabetes group. ADMSCs-ex administration attenuated this upregulation. The upregulation of S100A9 was confirmed in wound tissues from diabetic rats, as well as neutrophils induced by high glucose. ADMSCs-ex administration significantly reduced S100A9 protein expression via delivering miR-92a-1-5p in vitro. In vivo study showed that miR-92a-1-5p knockdown obstructed the promotional effect of ADMSCs-ex on diabetic wound healing and NETs formation. In conclusion, this study provides evidence that ADMSCs-ex accelerate diabetic wounds healing via a conserved miR-92a-1-5p/S100A9 pathway. These findings suggest that these exosomes loaded with miR-92a-1-5p may represent a promising therapeutic approach for the management of impaired healing of diabetic wounds.