Augmentation of hypoxia-inducible factor-1-alpha in reinfused blood cells enhances diabetic ischemic wound closure in mice

Diabetes-associated dysfunction in angiogenesis predominantly contributes to impairment of wound closure, but a role of hypoxia-inducible factor 1 alpha (HIF-1a) in the process remain poorly understood. Here, we examined whether expression of HIF-1a in re-infused blood cells may improve the diabetic wound closure in mice. We found that that expression of HIF-1a in re-infused isogeneic blood cells significantly improved diabetic wound healing in mice, seemingly through augmentation of wound-associated angiogenesis. Mechanistically, expression of HIF-1a in re-infused blood cells significantly increased macrophage infiltration at the wound site, and macrophages produced vascular endothelial growth factor A (VEGF-A) to promote wound-associated angiogenesis. Together, our data suggest that augmentation of HIF-1a in reinfused blood cells may enhance diabetic ischemic wound closure.