Strengthening the skin with topical delivery of keratinocyte growth factor-1 using a novel DNA plasmid

Mol Ther. 2014 Apr;22(4):752-61. doi: 10.1038/mt.2014.2. Epub 2014 Jan 17.

Abstract

Fragile skin, susceptible to decubitus ulcers and incidental trauma, is a problem particularly for the elderly and for those with spinal cord injury. Here, we present a simple approach to strengthen the skin by the topical delivery of keratinocyte growth factor-1 (KGF-1) DNA. In initial feasibility studies with the novel minimalized, antibiotic-free DNA expression vector, NTC8385-VA1, the reporter genes luciferase and enhanced green fluorescent protein were delivered. Transfection was documented when luciferase expression significantly increased after transfection. Microscopic imaging of enhanced green fluorescent protein-transfected skin showed green fluorescence in hair follicles, hair shafts, and dermal and superficial epithelial cells. With KGF-1 transfection, KGF-1 mRNA level and protein production were documented with quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry, respectively. Epithelial thickness of the transfected skin in the KGF group was significantly increased compared with the control vector group (26 ± 2 versus 16 ± 4 µm) at 48 hours (P = 0.045). Dermal thickness tended to be increased in the KGF group (255 ± 36 versus 162 ± 16 µm) at 120 hours (P = 0.057). Biomechanical assessment showed that the KGF-1-treated skin was significantly stronger than control vector-transfected skin. These findings indicate that topically delivered KGF-1 DNA plasmid can increase epithelial thickness and strength, demonstrating the potential of this approach to restore compromised skin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Topical
  • Animals
  • DNA / administration & dosage
  • DNA / genetics
  • Fibroblast Growth Factor 7 / administration & dosage
  • Fibroblast Growth Factor 7 / genetics*
  • Gene Transfer Techniques*
  • Genetic Therapy*
  • Humans
  • Mice
  • Plasmids / administration & dosage
  • Skin Abnormalities / genetics*
  • Skin Abnormalities / therapy
  • Wound Healing / genetics

Substances

  • Fibroblast Growth Factor 7
  • DNA