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Abstract

BACKGROUND:

Diabetic foot ulcers threaten the patients' health even survival. It lacks of an effective treatment. But stem cell therapy possesses special advantages and potential in tissue regeneration and wound healing.

OBJECTIVE:

To assess the therapeutic effect of subcutaneous transplantation of bone marrow mesenchymal stem cells around the wounds of diabetic foot ulcers in rats.

METHODS:

Bone marrow mesenchymal stem cells were separated from male Wistar rats and cultured by the whole bone marrow adherence method until the third generation. Then the bone marrow mesenchymal stem cells were labeled by 4,6-diamino-2-phenylindole in vitro. Thirty-six male Wistar rats were randomly divided into three groups: (1) cell transplantation group in which diabetic experimental rats were subcutaneously injected with bone marrow mesenchymal stem cells, (2) non-diabetic control group and (3) diabetic control group. Diabetic foot ulcer model was established by removing a 3 mm × 7 mm rectangular full-thickness skin from two feet of diabetic rats. The wound healing and gene and protein expression levels were evaluated at 2, 5, 8 and 11 days after bone marrow mesenchymal stem cell transplantation.

RESULTS AND CONCLUSION:

The wound healing rates were as follows: non-diabetic controls > cell transplantation group > diabetic controls, while there were no significant differences between cell transplantation group and diabetic control group. The intensity and distribution of the fluorescence was highest on day 5 after transplantation to the frozen sections in the cell transplantation group. Results of hematoxylin-eosin staining revealed that the granulation tissues in the non-diabetic control group were thicker than that in other groups on day 5, and granulation tissue in cell transplantation group was thicker than that in the diabetic control group. Immunohistochemistry of CD31 demonstrated that the mean number of small blood vessels in the cell transplantation group was greater than that in the diabetic control group on day 8 and day 11 (P < 0.05). However, the mean number of Ki-67-positive cells in the cell transplantation group was greater than that in the diabetic control group at each time point (P < 0.01). The results of enzyme-linked immunosorbent assay and reverse transcription-PCR showed that the expression levels of vascular endothelial growth factor in the non-diabetic control group were higher than those in the cell transplantation group and diabetic control group, while the expression levels of vascular endothelial growth factor in the cell transplantation group were significantly higher than those in diabetic control group on day 5 and 8 (P < 0.01). The subcutaneous transplantation of bone marrow mesenchymal stem cells around the wounds can significantly promote wound healing of diabetic foot ulcers in rats. This effect may be followed by the increased expression of vascular endothelial growth factor in wound tissues.

RESULTS AND CONCLUSION:

Wan JB, Cai Q, Liu Y. Subcutaneous transplantation of bone marrow mesenchymal stem cells for repairing diabetic foot ulcers in rats. Zhongguo Zuzhi Gongcheng Yanjiu. 2013;17(10):1766-1772.

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