Article
DFO preconditioning restores the therapeutic potential of diabetic ASCs
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Published: | August 16, 2017 |
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Introduction: A hallmark of diabetes mellitus is the breakdown of almost every reparative process in the human body, leading to critical impairments of wound healing. Currently, adipose-derived stem cells (ASCs) are considered to be a promising source for cell therapeutics targeting diabetic wounds. However, functionality of these cells is impaired by diabetes which can result from a defect in hypoxiainducible 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 this compromised angiogenic pathway for attenuating diabetes-associated deficits in cutaneous wound healing.
Materials and methods: Diabetic ASCs from db/db mice were treated in vitro with DFO and assessed for the expression of key mediators of neovascularization and tissue regeneration at mRNA and protein levels, using qRT-PCR and ELISA. Additionally a matrix tubulization assay was performed. In vivo experiments were conducted using a humanized excisional wound model and histology was taken upon complete healing.
Results: DFO remarkably enhanced expression of regenerative genes and protein levels compared to untreated samples. Compromised angiogenic potential of diabetic ASCs was restored in the tubulization assay. DFO treatment further significantly enhanced the therapeutic effect of db/db ASCs which could be confirmed by CD31 staining demonstrating improved neovascularization.
Conclusion: DFO preconditioning restored the therapeutic potential of diabetic ASCs resulting in enhanced regeneration.