Hypoxic adipose‐derived stem cell exosomes as carriers of miR‐100‐5p to enhance angiogenesis and suppress inflammation in diabetic foot ulcers
Hong Liu, Fei Hao, Bangtao Chen
Abstract
Diabetic foot ulcer (DFU) is a severe diabetes complication characterized by impaired angiogenesis and chronic inflammation, leading to delayed wound healing. Exosomes (Exo) derived from hypoxic adipose-derived stem cells (H-ADSCs-Exo) show potential as therapeutic carriers. This study investigates the role of H-ADSCs-Exo carrying miR-100-5p in DFU healing. ADSCs were isolated, characterized, and their Exo analyzed via transmission electron microscopy, nanoparticle tracking analysis, and Western blot. Transcriptome sequencing identified miR-100-5p as a key modulator of angiogenesis and inflammation. In vitro, H-ADSCs-Exo enhanced human umbilical vein endothelial cell and fibroblast proliferation, migration, and tube formation. In a rat DFU model, H-ADSCs-Exo administration reduced ulcer size, increased angiogenesis (VEGF/CD31 expression), and decreased inflammatory markers (TNF-α, IL-6). miR-100-5p overexpression further amplified these effects, demonstrating its critical role in Exo-mediated healing. These findings highlight the therapeutic potential of H-ADSCs-Exo in DFU treatment, offering insights into cell signaling mechanisms and paving the way for miRNA-based regenerative therapies.