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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

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... Full description

Journal Title: Gene Therapy Aug 2002, pp.1065-74
Main Author: Jeschke, M
Other Authors: Richter, G , Höfstädter, F , Herndon, D , Perez-Polo, J-R
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 09697128 ; E-ISSN: 14765462 ; DOI: 10.1038/sj.gt.3301732
Link: http://search.proquest.com/docview/218672294/?pq-origsite=primo
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title: Non-viral liposomal keratinocyte growth factor (KGF) cDNA gene transfer improves dermal and epidermal regeneration through stimulation of epithelial and mesenchymal factors
format: Article
creator:
  • Jeschke, M
  • Richter, G
  • Höfstädter, F
  • Herndon, D
  • Perez-Polo, J-R
subjects:
  • Animals–Metabolism
  • Apoptosis–Pathology
  • Burns–Therapy
  • Burns–Metabolism
  • Burns–Administration & Dosage
  • Cell Division–Physiology
  • Collagen–Genetics
  • DNA, Complementary–Metabolism
  • Epidermis–Methods
  • Fibroblast Growth Factor 7–Metabolism
  • Fibroblast Growth Factors–Pathology
  • Fibroblast Growth Factors–Pathology
  • Gene Transfer Techniques–Pathology
  • Genetic Therapy–Pathology
  • Insulin-Like Growth Factor I–Pathology
  • Liposomes–Pathology
  • Male–Pathology
  • Rats–Pathology
  • Rats, Sprague-Dawley–Pathology
  • Regeneration–Pathology
  • Skin–Pathology
  • Skin Physiological Phenomena–Pathology
  • Transfection–Pathology
  • Wound Healing–Pathology
  • DNA, Complementary
  • Fgf7 Protein, Rat
  • Liposomes
  • Fibroblast Growth Factor 7
  • Fibroblast Growth Factors
  • Insulin-Like Growth Factor I
  • Collagen
ispartof: Gene Therapy, Aug 2002, pp.1065-74
description: 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 microg, vehicle), or liposomes plus the KGF cDNA (2.2 microg) and LacZ cDNA (0.2 microg). Transfection was confirmed by histochemical assays for beta-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.
language: eng
source:
identifier: ISSN: 09697128 ; E-ISSN: 14765462 ; DOI: 10.1038/sj.gt.3301732
fulltext: fulltext
issn:
  • 09697128
  • 0969-7128
  • 14765462
  • 1476-5462
url: Link


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titleNon-viral liposomal keratinocyte growth factor (KGF) cDNA gene transfer improves dermal and epidermal regeneration through stimulation of epithelial and mesenchymal factors
creatorJeschke, M ; Richter, G ; Höfstädter, F ; Herndon, D ; Perez-Polo, J-R
ispartofGene Therapy, Aug 2002, pp.1065-74
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subjectAnimals–Metabolism ; Apoptosis–Pathology ; Burns–Therapy ; Burns–Metabolism ; Burns–Administration & Dosage ; Cell Division–Physiology ; Collagen–Genetics ; DNA, Complementary–Metabolism ; Epidermis–Methods ; Fibroblast Growth Factor 7–Metabolism ; Fibroblast Growth Factors–Pathology ; Fibroblast Growth Factors–Pathology ; Gene Transfer Techniques–Pathology ; Genetic Therapy–Pathology ; Insulin-Like Growth Factor I–Pathology ; Liposomes–Pathology ; Male–Pathology ; Rats–Pathology ; Rats, Sprague-Dawley–Pathology ; Regeneration–Pathology ; Skin–Pathology ; Skin Physiological Phenomena–Pathology ; Transfection–Pathology ; Wound Healing–Pathology ; DNA, Complementary ; Fgf7 Protein, Rat ; Liposomes ; Fibroblast Growth Factor 7 ; Fibroblast Growth Factors ; Insulin-Like Growth Factor I ; Collagen
descriptionKeratinocyte 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 microg, vehicle), or liposomes plus the KGF cDNA (2.2 microg) and LacZ cDNA (0.2 microg). Transfection was confirmed by histochemical assays for beta-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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titleNon-viral liposomal keratinocyte growth factor (KGF) cDNA gene transfer improves dermal and epidermal regeneration through stimulation of epithelial and mesenchymal factors
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titleNon-viral liposomal keratinocyte growth factor (KGF) cDNA gene transfer improves dermal and epidermal regeneration through stimulation of epithelial and mesenchymal factors
authorJeschke, M ; Richter, G ; Höfstädter, F ; Herndon, D ; Perez-Polo, J-R
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5Cell Division–Physiology
6Collagen–Genetics
7DNA, Complementary–Metabolism
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9Fibroblast Growth Factor 7–Metabolism
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abstractKeratinocyte 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 microg, vehicle), or liposomes plus the KGF cDNA (2.2 microg) and LacZ cDNA (0.2 microg). Transfection was confirmed by histochemical assays for beta-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.
copHoundmills
pubNature Publishing Group
doi10.1038/sj.gt.3301732
urlhttp://search.proquest.com/docview/218672294/
issue16
volume9
date2002-08-01