FGF-7 expression enhances the performance of bioengineered skin

Mol Ther. 2004 Jul;10(1):76-85. doi: 10.1016/j.ymthe.2004.04.013.

Abstract

To improve the performance of bioengineered skin, we used a recombinant retrovirus encoding FGF-7 to modify diploid human keratinocytes genetically. Control or FGF-7-expressing keratinocytes were seeded onto acellular human dermis to form bioengineered skin. Gene-modified skin secreted significant levels of FGF-7 and formed a thicker and hyperproliferative epidermis with about four times the number of cells per square centimeter. Secretion of an endogenous trophic factor, VEGF, was increased approximately 5-fold. Migration of FGF-7-expressing keratinocytes was stimulated as was the self-healing of bioengineered skin expressing FGF-7. When tested in a bacterial infection model, the antimicrobial properties of FGF-7-expressing skin were increased >500-fold against both gram-negative and gram-positive bacteria. After transplantation to full-thickness wounds on athymic mice, skin expressing FGF-7 was revascularized more rapidly. These results demonstrate that genetic modification can be used to enhance performance and that expression of FGF-7 augments several properties important to the wound-healing properties of bioengineered skin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides / genetics
  • Antimicrobial Cationic Peptides / metabolism
  • Bacterial Infections / metabolism
  • Cell Movement
  • Fibroblast Growth Factor 7
  • Fibroblast Growth Factors / analysis
  • Fibroblast Growth Factors / genetics*
  • Fibroblast Growth Factors / metabolism
  • Genetic Therapy
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / metabolism*
  • Keratinocytes / transplantation
  • Mice
  • Neovascularization, Physiologic
  • Retroviridae / genetics
  • Skin / cytology
  • Skin / metabolism
  • Skin Transplantation / methods*
  • Tissue Engineering / methods*
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Wound Healing

Substances

  • Antimicrobial Cationic Peptides
  • FGF7 protein, human
  • Fgf7 protein, mouse
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 7
  • Fibroblast Growth Factors