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Non-viral liposomal keratinocyte growth factor (KGF) cDNA gene transfer improves dermal and epidermal regeneration through stimulation of epithelial and mesenchymal factors

Gene Therapy volume 9, pages 1065–1074 (2002)Cite this article

Abstract

Keratinocyte growth factor (KGF) stimulates epithelial cell differentiation and proliferation, which are of major importance for wound healing. Local protein administration, however, has been shown to be ineffective due to enzymes and proteases in the wound fluid. We hypothesized that delivering KGF as a non-viral liposomal cDNA gene complex is a new approach that would effectively enhance dermal and epidermal regeneration. Twenty-two rats were given an acute wound and divided into two groups to receive weekly subcutaneous injections of liposomes plus the LacZ gene (0.2 μg, vehicle), or liposomes plus the KGF cDNA (2.2 μg) and LacZ cDNA (0.2 μg). Transfection was confirmed by histochemical assays for β-galactosidase. Planimetry, histological and immunohistochemical techniques were used to determine protein expression, dermal and epidermal regeneration. Transfection and subsequent KGF expression was found in diving cells in the granulation tissue. Epidermal regeneration was improved by 170% in rats receiving the KGF cDNA constructs by exhibiting the most rapid area and linear wound re-epithelialization, P < 0.0001. KGF improved epidermal cell net balance by increasing skin cell proliferation and decreasing skin cell apoptosis, P < 0.0001. Dermal regeneration was further improved in KGF cDNA treated animals by an increased collagen deposition and morphology, P < 0.0001. KGF cDNA increased neo-vascularization and concomitant VEGF concentrations when compared with vehicle, P < 0.01. KGF cDNA did not only stimulate epithelial cells, but also mesenchymal cells through increases in IGF-I concentration, P < 0.005. Liposomes containing the KGF cDNA gene constructs were effective in improving epidermal and dermal regeneration. KGF gene transfer to acute wounds may represent a new therapeutic strategy to enhance wound healing.

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Acknowledgements

This study was supported by the Deutsche Forschungsgemeinschaft (DFG Je 233/1-2). This manuscript is dedicated to my son Alexander, who was born 8 July 2001.

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Authors and Affiliations

  1. Klinik und Poliklinik für Chirurgie, University of Regensburg, Regensburg, Germany

    MG Jeschke & K-W Jauch

  2. Institut für Pathologie, University of Regensburg, Regensburg, Germany

    G Richter & F Höfstädter

  3. Shriners Hospital for Children and Department of Surgery, University Texas Medical Branch, Galveston, TX, USA

    DN Herndon

  4. Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, TX, USA

    J-R Perez-Polo

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  1. MG Jeschke
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Jeschke, M., Richter, G., Höfstädter, F. et al. Non-viral liposomal keratinocyte growth factor (KGF) cDNA gene transfer improves dermal and epidermal regeneration through stimulation of epithelial and mesenchymal factors. Gene Ther 9, 1065–1074 (2002). https://doi.org/10.1038/sj.gt.3301732

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