Adipose-derived mesenchymal stem cells promote diabetic wound healing through ALDOA secretion

Diabetic wound healing is impaired by hyperglycemia-induced metabolic dysregulation and chronic inflammation. Adipose-derived mesenchymal stem cell (ADSC)-derived exosomes, noted for rich bioactive molecules and immunomodulation, are promising for wound healing, but their mechanisms in diabetic wounds remain unclear. This study investigated their impact and mechanism.

HaCaT cells were treated with high glucose to mimic in vitro diabetic conditions. C57BL/6 mice were treated with streptozotocin to construct the diabetic mouse model and induce skin wound. Exosomes were characterized by transmission electron microscopy and nanoparticle tracking analysis. Its role in vitro was evaluated by measuring cell viability, transwell and scratch wound assays. Hematoxylin-eosin and Masson staining were used to evaluate the pathological changes in mouse skin tissues. Microarray analysis, RNA sequencing and KEGG pathway enrichment analysis were performed to investigate the underlying mechanisms.

Results showed that ADSC-derived exosomes enhanced migration and ECAR levels in HG-induced HaCaT cells, and promoted wound healing in diabetic mice. ALODA was enriched in glycolysis pathway, and its expression was reduced in HG-induced HaCaT cells, which was increased following exosomes treatment, even higher than that in the control group. ALDOA knockdown in exosomes inhibited migration and glycolytic activity increased by ADSCs-derived exosomes in HG-induced HaCaT cells. Moreover, ALDOA overexpression promoted migration and glycosis in HG-induced HaCaT cells.

These findings indicate that ADSC-derived exosomes enhance diabetic wound healing by upregulating ALDOA and promoting glycolysis, providing new experimental evidence for developing exosome-based therapies targeting impaired wound healing in diabetic patients.