Treatment of diabetic wounds with fetal murine mesenchymal stromal cells enhances wound closure

Abstract

Diabetes impairs multiple aspects of the wound-healing response. Delayed wound healing continues to be a significant healthcare problem for which effective therapies are lacking. We have hypothesized that local delivery of mesenchymal stromal cells (MSC) at a wound might correct many of the wound-healing impairments seen in diabetic lesions. We treated excisional wounds of genetically diabetic (Db-/Db-) mice and heterozygous controls with either MSC, CD45(+) cells, or vehicle. At 7 days, treatment with MSC resulted in a decrease in the epithelial gap from 3.2 +/- 0.5 mm in vehicle-treated wounds to 1.3 +/- 0.4 mm in MSC-treated wounds and an increase in granulation tissue from 0.8 +/- 0.3 mm(2) to 2.4 +/- 0.6 mm(2), respectively (mean +/- SD, P < 0.04). MSC-treated wounds also displayed a higher density of CD31(+) vessels and exhibited increases in the production of mRNA for epidermal growth factor, transforming growth factor beta 1, vascular endothelial growth factor, and stromal-derived growth factor 1-alpha. MSC also demonstrated greater contractile ability than fibroblast controls in a collagen gel contraction assay. The effects of locally applied MSC are thus sufficient to improve healing in diabetic mice. Possible mechanisms of this effect include augmented local growth-factor production, improved neovascularization, enhanced cellular recruitment to wounds, and improved wound contraction.