Adipose-derived stem cells improve neovascularization in ischemic flaps in diabetic mellitus through HIF-1α/VEGF pathway

W.-Y. Yu, W. Sun, D.-J. Yu, T.-L. Zhao, L.-J. Wu, H.-R. Zhuang

Department of Plastic and Anesthetic Surgery, The Second Hospital Affiliated to Soochow University, Jiangsu Sheng, China

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• Plastic Surgery

OBJECTIVE: To investigate the improvement effect of adipose-derived stem cells on neovascularization in an ischemic flap in diabetes mellitus (DM), and to explore the mechanism of hypoxia-inducible factor 1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway.

MATERIALS AND METHODS: A total of 60 male Sprague-Dawley (SD) rats were divided into control group, model group, and adipose-derived stem cells (ADSCs) group. The survival rate of the flap and the number of new blood vessels were measured. The content of VEGF was determined by enzyme-linked immunosorbent assay (ELISA) kit. Then, the expressions of HIF-1α and VEGF in each group were measured by immunohistochemistry. Reverse transcriptase polymerase chain reaction (RT-PCR) method and Western blotting assay were used to detect the mRNA and protein expression of HIF-1α and VEGF in each group.

RESULTS: Compared with control group, the flap survival rate of model group was decreased significantly, and the number of new blood vessels was also decreased significantly. Compared with model group, the flap survival rate of ADSCs group was increased significantly, and the number of new blood vessels was also increased significantly. The results of ELISA showed that compared with control group, the level of VEGF in model group was lower than that in model group, and the level of VEGF in the ADSC group was significantly higher than that in the model group. IHC results showed that both HIF-1α and VEGF proteins were decreased significantly in model group, whereas the expression of HIF-1α and VEGF in the ADSCs group was increased significantly. The results of RT-PCR and the Western blotting showed the mRNA and protein expressions in model group were all decreased, while those in ADSCs group were significantly increased (p < 0.05).

CONCLUSIONS: ADSCs can improve the neovascularization of diabetic ischemic skin by regulating the HIF-1α/VEGF pathway.

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