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

ABSTRACT: 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.

SUBMITTER: Wang H

PROVIDER: S-EPMC5768400 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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

Wang Huan H Feng Yufeng Y Jin Xiaoju X Xia Rong R Cheng Yong Y Liu Xiaoqian X Zhu Nana N Zhou Xun X Yin Lei L Guo Jianrong J

Oncotarget 20171213 69

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-assoc ...[more]

PMID: 29371983

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Project description:Diabetes can impair wound closure, which can give rise to major clinical problems. Most treatments for wound repair in diabetes remain ineffective. This study aimed to investigate the influence on wound closure of treatments using expanded human cord blood CD34(+) cells (CB-CD34(+) cells), freshly isolated CB-CD34(+) cells and a cytokine cocktail. The test subjects were mice with streptozotocin-induced diabetes. Wounds treated with fresh CB-CD34(+) cells showed more rapid repair than mice given the PBS control. Injection of expanded CB-CD34(+) cells improved wound closure significantly, whereas the injection of the cytokine cocktail alone did not improve wound repair. The results also demonstrated a significant decrease in epithelial gaps and advanced re-epithelialization over the wound bed area after treatment with either expanded CB-CD34(+) cells or freshly isolated cells compared with the control. In addition, treatments with both CB-CD34(+) cells and the cytokine cocktail were shown to promote recruitment of CD31(+)-endothelial cells in the wounds. Both the CB-CD34(+) cell population and the cytokine treatments also enhanced the recruitment of CD68-positive cells in the early stages (day 3) of treatment compared with PBS control, although the degree of this enhancement was found to decline in the later stages (day 9). These results demonstrated that expanded CB-CD34(+) cells or freshly isolated CB-CD34(+) cells could accelerate wound repair by increasing the recruitment of macrophages and capillaries and the reepithelialization over the wound bed area. Our data suggest an effective role in wound closure for both ex vivo expanded CB-CD34(+) cells and freshly isolated cells, and these may serve as therapeutic options for wound treatment for diabetic patients. Wound closure acceleration by expanded CB-CD34(+) cells also breaks the insufficient quantity obstacle of stem cells per unit of cord blood and other stem cell sources, which indicates a broader potential for autologous transplantation.

Dataset Information

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

Publications

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

Similar Datasets

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