Treatment of diabetic wounds with fetal murine mesenchymal stromal cells enhances wound closure
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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 mm2 to 2.4 ± 0.6 mm2, 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.
KeywordsStromal progenitor cells Mesenchymal stromal cells Mesenchymal stem cells Wound healing Diabetes Mouse (C57BKS strains)
- Anker PS in ’t, Noort WA, Scherjon SA, Kleijburg-van der Keur C, Kruisselbrink AB, Bezooijen RL van, Beekhuizen W, Willemze R, Kanhai HH, Fibbe WE (2003) Mesenchymal stem cells in human second-trimester bone marrow, liver, lung, and spleen exhibit a similar immunophenotype but a heterogeneous multilineage differentiation potential. Haematologica 88:845–852Google Scholar
- Digirolamo CM, Stokes D, Colter D, Phinney DG, Class R, Prockop DJ (1999) Propagation and senescence of human marrow stromal cells in culture: a simple colony-forming assay identifies samples with the greatest potential to propagate and differentiate. Br J Haematol 107:275–281PubMedCrossRefGoogle Scholar
- Nagaya N, Fujii T, Iwase T, Ohgushi H, Itoh T, Uematsu M, Yamagishi M, Mori H, Kangawa K, Kitamura S (2004) Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis. Am J Physiol Heart Circ Physiol 287:H2670–H2676PubMedCrossRefGoogle Scholar
- Wieman TJ, Smiell JM, Su Y (1998) Efficacy and safety of a topical gel formulation of recombinant human platelet-derived growth factor-BB (becaplermin) in patients with chronic neuropathic diabetic ulcers. A phase III randomized placebo-controlled double-blind study. Diabetes Care 21:822–827PubMedCrossRefGoogle Scholar