PRDX4-enriched exosomes from adipose stem cells enhance diabetic wound repair through angiogenic activation.

BACKGROUND

Diabetic (DM) wounds are a major challenge in dermatology. Despite the therapeutic effectiveness of stem cell therapy in wound repair, clinical applications remain limited. We investigated whether adipose-derived exosomes (Exos) can promote healing in diabetic mice.

METHODS

High-throughput sequencing (HTS) was employed to study abnormal circular RNA expression in ulcerated tissue with or without adipose-derived stem cell (ADSC)-Exo treatment. EPCs were employed to analyze reactive oxygen species (ROS), apoptosis, and angiogenic differentiation functions. A DM ulceration mouse model was generated and Exo therapeutic effects were investigated.

RESULTS

Data demonstrated that ADSC-Exo treatment enhances wound healing (WH) of diabetic mice through inhibiting ROS deposition and restoring angiogenic function under high glucose (HG) conditions. The HTS in the current research revealed that ADSC-Exo treatment resulted in altered gene expression, including of peroxiredoxin 4 (PRDX4). PRDX4 downregulation inhibited the Exo protective effects on WH. PRDX4 overexpression inhibited HG-induced EPC dysfunction and augmented Exo therapeutic effects on WH.

CONCLUSION

Our data indicated that Exos derived from ADSCs promoted diabetic wound (DW) healing through delivering PRDX4 and improving endothelial cell function, which aids in the development of stem cell-based therapeutic treatments of DWs.