Adipose-Derived Stem Cell Exosomes Accelerate Diabetic Wound Healing by Suppressing AURKB and Activating the Rap1 Signaling Pathway

Diabetic wounds are characterized by impaired angiogenesis, persistent inflammation, and delayed tissue remodeling, yet effective cell-free therapies remain limited. Adipose-derived stem cell exosomes (ADSC-exos) possess pro-angiogenic and anti-inflammatory properties, but the precise molecular mechanisms are incompletely defined. We harvested ADSC-exos from rat adipose tissue and then evaluated their impact on high-glucose (HG)-induced human umbilical vein endothelial cells (HUVECs), using Cell Counting Kit-8, 5-ethynyl-2’-deoxyuridine incorporation, scratch wound healing, and tube formation assays. In streptozotocin-induced diabetic rats with dorsal wounds, ADSC-exos were injected subcutaneously. Wound closure, thermal hyperalgesia, collagen deposition, and Ki67/CD31 were evaluated. Transcriptomic sequencing and protein-protein interaction network analysis identified Aurora kinase B (AURKB) as a candidate mediator. AURKB knockdown, overexpression, and Ras-associated protein 1 (Rap1) inhibition (GGTI298 and si-RAP1B) were used to validate the AURKB/Rap1 axis. ADSC-exos restored HG-impaired HUVEC viability, proliferation, migration, and tube formation. In diabetic rats, ADSC-exos accelerated wound closure, reduced thermal hyperalgesia, lowered inflammatory cytokines, enhanced collagen deposition, and increased Ki67-positive proliferating cells and CD31-positive vessels. Transcriptomic analysis revealed that ADSC-exos downregulated AURKB. AURKB knockdown further improved wound healing and angiogenesis, and reduced thermal hyperalgesia. AURKB overexpression abolished the protective effects of ADSC-exos on HUVECs. Mechanistically, ADSC-exos upregulated RAP1A and RAP1B expression through AURKB suppression, and both GGTI298 and si-RAP1B reversed the protective effects of AURKB knockdown on HUVECs. In conclusion, ADSC-exos accelerate diabetic wound healing by suppressing AURKB and activating the Rap1 signaling pathway, identifying the AURKB/Rap1 axis as a novel therapeutic target and supporting ADSC-exos as a promising cell-free strategy. ADSC-exos accelerated diabetic wound healing and reduced thermal hyperalgesia. ADSC-exos suppressed AURKB expression in diabetic wound tissues. AURKB silencing further enhanced the effects of ADSC-exos on diabetic wound repair. The AURKB/Rap1 axis is a novel target for cell-free therapy.