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

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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 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.

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Authors and Affiliations

  1. The Center for Fetal Research at The Children’s Hospital of Philadelphia, The University of Pennsylvania School of Medicine, Philadelphia, PA, 19104, USA

    Andrea T. Badillo, Robert A. Redden, Liping Zhang, Edward J. Doolin & Kenneth W. Liechty

  2. Abramson Research Center, Rm 1116E, 3615 Civic Center Blvd, Philadelphia, 19104, USA

    Kenneth W. Liechty

Authors
  1. Andrea T. Badillo
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  2. Robert A. Redden
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  3. Liping Zhang
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  4. Edward J. Doolin
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  5. Kenneth W. Liechty
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Correspondence to Kenneth W. Liechty.

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Badillo, A.T., Redden, R.A., Zhang, L. et al. Treatment of diabetic wounds with fetal murine mesenchymal stromal cells enhances wound closure. Cell Tissue Res 329, 301–311 (2007). https://doi.org/10.1007/s00441-007-0417-3

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  • DOI: https://doi.org/10.1007/s00441-007-0417-3

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