Open AccessDeferoxamine preconditioning to restore impaired HIF ‐1α‐mediated angiogenic mechanisms in adipose‐derived stem cells from STZ ‐induced type 1 diabetic rats
Author(s) -
Mehrabani M.,
Najafi M.,
Kamarul T.,
Mansouri K.,
Iranpour M.,
Nematollahi M. H.,
GhaziKhansari M.,
Sharifi A. M.
Publication year - 2015
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12209
Subject(s) - angiogenesis , neovascularization , deferoxamine , matrix metalloproteinase , streptozotocin , vascular endothelial growth factor , in vivo , wound healing , matrix metalloproteinase inhibitor , pharmacology , chemistry , cancer research , medicine , immunology , diabetes mellitus , biology , endocrinology , microbiology and biotechnology , vegf receptors
Objectives Both excessive and insufficient angiogenesis are associated with progression of diabetic complications, of which poor angiogenesis is an important feature. Currently, adipose‐derived stem cells ( ADSC s) 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 ADSC s derived from streptozotocin ( STZ )‐induced type 1 diabetic rats (‘diabetic ADSC s’). Materials and methods Diabetic ADSC s were treated with DFO and compared to normal and non‐treated diabetic ADSC s for expression of HIF ‐1α, 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 ADSC s were determined by in vitro (in HUVEC s) and in vivo experiments including scratch assay, three‐dimensional tube formation testing and surgical wound healing models. Results DFO 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 ADSC s was restored by DFO both in vitro and in vivo experiments. Conclusion DFO preconditioning restored neovascularization potential of ADSC s derived from diabetic rats by affecting the HIF ‐1α pathway.