Effect of intramuscular bone marrow-derived mesenchymal stem cell transplantation in the leg for treatment of diabetic foot ulcers in rats / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To assess the therapeutic effect of intramuscular transplantation of bone-marrow derived mesenchymal stem cells (BM-MSCs) in the leg for treatment of diabetic foot ulcers (DFUs) in rats.</p><p><b>METHODS</b>Thirty-six male Wistar rats were randomly allocated into 3 equal groups, namely group A with DFUs on the bilateral hindlimb dorsum pedis and intramuscular transplantation of 4,6-diamino-2-phenylindole (DAPI)-labeled third-passage BM-MSCs from male Wistar rats into the leg, group B with nondiabetic foot ulcers, and group C with DFUs but without BM-MSC transplantation. On days 2, 5, 8 and 11 posttransplantation, the rate of wound healing was evaluated, the labeled BM-MSCs in the wound tissues were traced on frozen sections, and the thickness of granulation tissues was measured with HE staining. Immunohistochemistry was performed to detect the expression of CD31 and Ki-67, and the expression of vascular endothelial growth factor (VEGF) in the wound tissues was detected by ELISA and RT-PCR.</p><p><b>RESULTS</b>The rats in group B showed significantly faster wound closure than those in the other two groups (P<0.05). The rate of wound healing was greater in group A than in group C on days 8 and 11 (P<0.05). The fluorescence intensity and area on the frozen sections were the highest on day 5 posttransplantation in group A, which had a granulation tissue thickness comparable with group B but greater than group C. The mean numbers of small blood vessels and cells positive for CD31 and Ki-67 expressions were similar between groups A and B, which showed significant differences from group C (P<0.05). On day 11, group A showed the highest VEGF expression in the wound tissues (P<0.001).</p><p><b>CONCLUSION</b>Intramuscular transplantation of BM-MSCs can significantly promote wound healing of DFUs in rats possibly as a result of increased expression of VEGF in the wound tissues.</p>