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

M. G. Jeschke, G. Richter, F. Höfstädter, David Herndon, J. R. Perez-Polo, K. W. Jauch

Research output: Contribution to journalArticle

59 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1065-1074
Number of pages10
JournalGene Therapy
Volume9
Issue number16
DOIs
StatePublished - 2002

Fingerprint

Fibroblast Growth Factor 7
Regeneration
Complementary DNA
Skin
Genes
Liposomes
Re-Epithelialization
Wound Healing
Transfection
Wounds and Injuries
Epithelial Cells
Cell Proliferation
Galactosidases
Histological Techniques
Diving
Lac Operon
Granulation Tissue
Subcutaneous Injections
Insulin-Like Growth Factor I
Vascular Endothelial Growth Factor A

Keywords

  • Burns
  • Gene therapy
  • Growth factors
  • Skin
  • Wound healing

ASJC Scopus subject areas

  • Genetics

Cite this

Non-viral liposomal keratinocyte growth factor (KGF) cDNA gene transfer improves dermal and epidermal regeneration through stimulation of epithelial and mesenchymal factors. / Jeschke, M. G.; Richter, G.; Höfstädter, F.; Herndon, David; Perez-Polo, J. R.; Jauch, K. W.

In: Gene Therapy, Vol. 9, No. 16, 2002, p. 1065-1074.

Research output: Contribution to journalArticle

Jeschke, M. G. ; Richter, G. ; Höfstädter, F. ; Herndon, David ; Perez-Polo, J. R. ; Jauch, K. W. / Non-viral liposomal keratinocyte growth factor (KGF) cDNA gene transfer improves dermal and epidermal regeneration through stimulation of epithelial and mesenchymal factors. In: Gene Therapy. 2002 ; Vol. 9, No. 16. pp. 1065-1074.
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