IGF-I gene transfer in thermally injured rats

M. G. Jeschke, R. E. Barrow, H. K. Hawkins, K. Yang, R. L. Hayes, B. J. Lichtenbelt, J. R. Perez-Polo, D. N. Herndon

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Exogenous insulin-like growth factor-I (IGF-I) is known to improve the pathophysiology of a thermal injury, however, deleterious side-effects have limited its utility. Cholesterol-containing cationic liposomes that encapsulate complementary DNA (cDNA) are nonviral carriers used for in vivo gene transfection. We propose that liposome IGF-I gene transfer will accelerate wound healing in burned rats and attenuate deleterious side-effects associated with high levels of IGF-I. To test this hypothesis IGF-I gene constructs, encapsulated in liposomes, were studied for their efficacy in modulating the thermal injury response. Thirty adult male Sprague-Dawley rats were given a 60% TBSA scald burn and randomly divided into three groups to receive weekly subcutaneous injections of liposomes plus the lacZ gene coding for β-galactosidase, liposomes plus cDNA for IGF-I and β-galactosidase or liposomes plus the rhIGF-I protein. Body weights and wound healing were measured. Muscle and liver dry/wet weights and IGF-I concentrations in serum, skin and liver were measured by radioimmunoassay. Transfection was confirmed by histochemical staining for β-galactosidase. Rats receiving the IGF-I cDNA constructs exhibited the most rapid wound reepithelialization and greatest increase in body weight and gastrocnemius muscle protein content (P < 0.05). Local IGF-I protein concentrations in the skin were higher when compared to liposomes containing only the lacZ gene (P < 0.05) Transfection was apparent in the cytoplasm of myofibroblasts, endothelial cells and macrophages of the granulation tissue. Liposomes containing the IGF-I gene constructs proved effective in preventing muscle protein wasting and preserving total body weight after a severe thermal injury.

Original languageEnglish (US)
Pages (from-to)1015-1020
Number of pages6
JournalGene Therapy
Volume6
Issue number6
DOIs
StatePublished - Jun 1 1999

Keywords

  • Growth factor
  • Insulin-like growth factor-I
  • Liposomes
  • Trauma
  • Wound healing

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'IGF-I gene transfer in thermally injured rats'. Together they form a unique fingerprint.

  • Cite this

    Jeschke, M. G., Barrow, R. E., Hawkins, H. K., Yang, K., Hayes, R. L., Lichtenbelt, B. J., Perez-Polo, J. R., & Herndon, D. N. (1999). IGF-I gene transfer in thermally injured rats. Gene Therapy, 6(6), 1015-1020. https://doi.org/10.1038/sj.gt.3300923