Deferoxamine preconditioning to restore impaired HIF-1-mediated angiogenic mechanisms in adipose-derived stem cells from STZ-induced type 1 diabetic rats

ObjectivesBoth excessive and insufficient angiogenesis are associated with progression of diabetic complications, of which poor angiogenesis is an important feature. Currently, adipose-derived stem cells (ADSCs) are considered to be a promising source to aid therapeutic neovascularization. However, functionality of these cells is impaired by diabetes which can result from a defect in hypoxia-inducible factor-1 (HIF-1), a key mediator involved in neovascularization. In the current study, we sought to explore effectiveness of pharmacological priming with deferoxamine (DFO) as a hypoxia mimetic agent, to restore the compromised angiogenic pathway, with the aid of ADSCs derived from streptozotocin (STZ)-induced type 1 diabetic rats (diabetic ADSCs'). Materials and methodsDiabetic ADSCs were treated with DFO and compared to normal and non-treated diabetic ADSCs for expression of HIF-1, VEGF, FGF-2 and SDF-1, at mRNA and protein levels, using qRT-PCR, western blotting and ELISA assay. Activity of matrix metalloproteinases -2 and -9 were measured using a gelatin zymography assay. Angiogenic potential of conditioned media derived from normal, DFO-treated and non-treated diabetic ADSCs were determined by invitro (in HUVECs) and invivo experiments including scratch assay, three-dimensional tube formation testing and surgical wound healing models. ResultsDFO remarkably enhanced expression of noted genes by mRNA and protein levels and restored activity of matrix metalloproteinases -2 and -9. Compromised angiogenic potential of conditioned medium derived from diabetic ADSCs was restored by DFO both invitro and invivo experiments. ConclusionDFO preconditioning restored neovascularization potential of ADSCs derived from diabetic rats by affecting the HIF-1 pathway.