Jeschke, M. G. and Richter, G. and Hofstadter, F. and Herndon, D. N. and Perez-Polo, J. R. and Jauch, K. W. (2002) Non-viral liposomal keratinocyte growth factor (KGF) cDNA gene transfer improves dermal and epidermal regeneration through stimulation of epithelial and mesenchymal factors. GENE THERAPY, 9 (16). pp. 1065-1074. ISSN 0969-7128
Full text not available from this repository.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 mug, vehicle), or liposomes plus the KGF cDNA (2.2 mug) and LacZ cDNA (0.2 mug). Transfection was confirmed by histochemical assays for p-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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHRONIC WOUNDS; CELL-DEATH; EXPRESSION; SKIN; ANGIOGENESIS; REPAIR; MODEL; MICE; wound healing; gene therapy; skin; bums; growth factors |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Oct 2021 06:04 |
| Last Modified: | 12 Oct 2021 06:04 |
| URI: | https://pred.uni-regensburg.de/id/eprint/40030 |
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