Exosomes derived from HISLA overexpressed-adipose stem cells accelerate wound healing in diabetic foot ulcers by regulating HIF-1α signal transduction.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Diabetic foot ulcers (DFUs), characterized by impaired angiogenesis and a chronic inflammatory milieu, represent a severe complication of diabetes. This study investigates the therapeutic potential of exosomes derived from HISLA-overexpressing adipose-derived stem cells (HISLA-ex) in enhancing DFU healing. In vitro, under high glucose conditions, HISLA-ex significantly elevated HISLA expression by approximately 3-fold in endothelial cells, markedly improving cell viability at 24-72 h in HMEC-1 cells, reducing pro-inflammatory cytokines IL-1 and IL-6, and enhancing tube formation capacity as evidenced by increased branching points and total tube length. Subsequently, a DFU rat model was established by inducing diabetes with streptozotocin followed by creation of a full-thickness cutaneous wound on the foot dorsum. HISLA-ex application substantially accelerated wound closure and modulated key angiogenic factors: upregulating VEGFA and Ang-1 while suppressing TSP-1. Furthermore, HISLA-ex shifted the helper T (Th)1/Th2 balance by inhibiting T-bet and pro-inflammatory cytokines (IFN-γ and TNF-α) and promoting GATA3 and anti-inflammatory cytokines (IL-4 and IL-13) in vivo and in vitro. Mechanistically, these effects were mediated through activation of the HIF-1α pathway, confirmed by both gain- and loss-of-function experiments, and abolished upon HIF-1α inhibition. Collectively, our

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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