Wound healing has always been a serious issue for doctors and primary health care systems. In addition, adipose stem cell-derived exosomes have been proven to play a positive and effective role in tissue repair and regeneration. A systematic review of these preclinical studies was performed to assess the efficacy of adipose stem cell-derived exosomes (ADSC-Exos) in treating wounds. This article aimed to study the effectiveness of ADSC-Exos for the treatment of animal skin wounds and includes a meta-analysis of exosomes from general wounds and diabetic ulcer wounds in in vitro models of animals to provide a theoretical basis for clinical translation.

A total of 19 studies with 356 animals were identified by searching the PubMed, Cochrane, MEDLINE Complete, Web of Science, CNKI and Wanfang databases from inception to 15 November 2022. No language or time restrictions were applied. Stata17 was used for all the data analyses.

The meta-analysis showed that ADSC-Exo therapy significantly improved the wound healing rate in the control group, except in the diabetes group on day 7. Day 7 of general wounds [standard mean difference (SMD) 2.87, 95% confidence interval (CI) 1.91–3.83)] and day 14 (SMD 2.89, 95%CI 1.47–4.30). Day 14 (SMD 3.43, 95%CI 1.28–5.58) of diabetic wounds. Other outcomes, such as blood vessel density, collagen deposition and wound re-epithelization, improved with the administration of ADSC-Exos.

A meta-analysis showed that ADSC-Exo therapy applied to general and diabetic wounds can promote neovascularization, improve epithelization and collagen fiber deposition, promote healing, and reduce scar formation. ADSC-Exos have broad potential in preclinical research and clinical fields.

Diabetic wounds represent the most common type of chronic wounds. Persistent inflammation and elevated oxidative stress are hallmark features of chronic wounds, where macrophage phenotypic polarization playing a critical role in the healing process. Adipose-derived mesenchymal stem cell exosomes (ADSC-exos) have shown promising therapeutic effects in the treatment of diabetic wounds by modulating macrophage function. This study aims to elucidate the specific downstream regulatory mechanisms through both in vitro and in vivo investigations.

A streptozotocin-induced diabetic mouse model and high glucose-stimulated RAW 264.7 macrophages were utilized to mimic diabetic microenvironments. Wound tissues were collected from patients with diabetic foot ulcer. A skin incision model was established in mice and ADSC-exos were given subcutaneously. Streptozotocin-induced diabetic myeloid-specific sirt1^−/− mice SIRT1 siRNA-transfected macrophages were employed to investigate the role of SIRT1 in vivo and in vitro. Wound healing rates were quantified. Mitochondrial function, lysosomal activity, autophagy flux, and inflammation status were systematically assessed.

In diabetic mice and high glucose-treated macrophages, lysosomal dysfunction preceded mitochondrial and autophagy flux impairments. SIRT1 expression was significantly reduced in both diabetic wound tissues and macrophages, accompanied by M1 macrophage polarization. SIRT1 interference experiments revealed that the impact of ADSC-exos on mitochondrial function, autophagy flux, and inflammatory response were partially dependent on SIRT1. Notably, the therapeutic effects of ADSC-exos on mitochondrial and autophagic pathways were markedly attenuated upon SIRT1 suppression.

These findings demonstrate that ADSC-exos promotes diabetic wound healing by restoring mitochondrial function and autophagy via SIRT1 activation. These findings highlight the therapeutic potential of ADSC-exos and provide a mechanistic foundation for future exosome engineering strategies.