Mesenchymal stem cells promote wound healing and effects on expression of matrix metalloproteinases-8 and 9 in the wound tissue of diabetic rats.

Diabetic foot ulcer (DFU) is a multifactorial complication of diabetes, mainly manifested as infection, ulcer or destruction of deep tissue and there is currently no effective treatment. Several pre-clinical and clinical studies have proved that the transplantation of mesenchymal stem cells (MSCs) improved wound healing. Here, we evaluated the therapeutic efficacy of human umbilical cord (hUC-MSCs) in DFU rat model. One dose of hUC-MSCs (1×106 cells) were subcutaneously injected around wounds in male SD rats. Wound healing was evaluated macroscopically (wound closure) every three days. In addition, we measured growth factors and specific proteins (MMP-9 and MMP-8) on Day 14 post hUC-MSCs transplantation. Results showed significant differences in the wound healing kinetics of lesions that received hUC-MSCs compared to lesions that received vehicle (PBS) (P<0.05). ELISA analyses indicated that MMP-9 protein contents were significantly upregulated in DFU animals, while MMP-8 were downregulated compared to the diabetic rats (P<0.05). After MSCs treatment, the level of MMP-9 and MMP-8 decreased and increased compared to the vehicle group, respectively. These findings suggest hUC-MSCs transplantation can ameliorate the healing process of DFU rats and a potential mechanism through which MSCs enhance DFU wound healing by decreasing MMP-9 expression and increasing MMP-8 expression. This study represents a promising opportunity to gain insight into how MSCs mediate wound healing.