Hypoxia-regulated miR-103-3p/FGF2 axis in adipose-derived stem cells promotes angiogenesis by vascular endothelial cells during ischemic tissue repair.

Summary

Hypoxia increased FGF2 expression and proliferation in ADSCs; co-culture enhanced endothelial migration and tube formation, which were inhibited by FGF2 knockdown or miR-103-3p overexpression. miR-103-3p directly targets FGF2, and its inhibition in ADSCs augmented angiogenesis and reduced necrosis in a nude mouse ischemic flap model.

Key Findings

• Hypoxia upregulated FGF2 in ADSCs and enhanced their proliferation.
• ADSCs promoted endothelial migration and tube formation; effects were inhibited by FGF2 knockdown.
• miR-103-3p directly targets FGF2; miR-103-3p overexpression suppressed, while its inhibition enhanced, endothelial angiogenic responses.
• In a nude mouse ischemic flap model, ADSC injection increased vessel formation and reduced necrosis, with maximal benefit when miR-103-3p was inhibited.

Clinical Implications

Preconditioning ADSCs by inhibiting miR-103-3p or boosting FGF2 may improve outcomes of cell-based therapies for ischemic flaps in reconstructive/cosmetic procedures. Safety, dosing, and delivery strategies for miRNA modulation require clinical development.

Limitations

• Single-species, nude mouse model; human translation and immunologic context remain uncertain.
• miRNA modulation safety, biodistribution, and off-target effects were not addressed.

Future Directions

Assess miR-103-3p/FGF2 modulation in large-animal models; develop delivery systems (e.g., exosomes, hydrogels) for localized miRNA manipulation; evaluate safety/efficacy in early-phase clinical trials.