FGF21-engineered ADSCs promote diabetic wound healing by mitigating ferroptosis and oxidative stress via the SIRT1/NRF2/GPX4 signaling pathway.

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)

Background ADSCs and growth factor-based therapies are widely investigated for diabetic wound healing. However, the clinical translation of ADSCs is limited by their biological instability under hyperglycemic conditions, while exogenous growth factors face challenges such as short half-life and high production costs. Here, we propose a novel strategy using FGF21-engineered ADSCs (ADSC FGF21 ), leveraging the dual advantages of stem cell paracrine effects and FGF21's established role in metabolic regulation, to target ferroptosis and oxidative stress, key pathological drivers of delayed wound healing in diabetes. Methods To investigate ferroptosis in diabetic wounds, we quantified iron accumulation, DNA oxidative damage (8-OHdG), and lipid peroxidation (MDA assay) in diabetic wound tissues. In vitro, high glucose (HG) treated HUVEC, a model for endothelial dysfunction, were subjected to 7-AAD staining, BODIPY C11-based lipid peroxidation assays, and transmission electron microscopy (TEM) to assess ferroptosis hallmarks. The therapeutic effects of ADSC FGF21 were evaluated through CCK-8 proliferation assays, scratch wound healing, and Matrigel-based tube formation assays under HG conditions. Mechanistic studies involved flow cytometry for ferroptosis distinction, qPCR/Western blot for SIRT1/NRF2/GPX4, AMPK pathway analysis, and immunofluorescence to track NF-κB p65 nuclear transl

Evidence level

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

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