IGF-I gene transfer in thermally injured rats

• Published in: Gene therapy Vol. 6; no. 6; pp. 1015 - 1020
• Main Authors: JESCHKE, M. G, BARROW, R. E, HAWKINS, H. K, YANG, K, HAYES, R. L, LICHTENBELT, B. J, PEREZ-POLO, J. R, HERNDON, D. N
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01-06-1999
• Subjects: Animals; Biological and medical sciences; Biotechnology; Body weight; Burns - therapy; Cholesterol; Complementary DNA; Cytoplasm; Endothelial cells; Fundamental and applied biological sciences. Psychology; Gastrocnemius muscle; Gene therapy; Gene transfer; Genetic Therapy - methods; Health. Pharmaceutical industry; Industrial applications and implications. Economical aspects; Insulin; Insulin-like growth factor I; Insulin-Like Growth Factor I - genetics; Insulin-like growth factors; LacZ gene; Liposomes; Liver; Macrophages; Male; Physical growth; Proteins; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Scald; Side effects; Thermal injury; Transfection; Wound Healing; β-Galactosidase; Skin disease; Rat; Injury; Rodentia; Liposome; Gene expression; Insulin like growth factor 1; Genetic transfer; Burn; Vertebrata; Mammalia; Gene; Polypeptide; Gene therapy; Vector
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/sj.gt.3300923

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 beta-galactosidase, liposomes plus cDNA for IGF-I and beta-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 beta-galactosidase. Rats receiving the IGF-I cDNA constructs exhibited the most rapid wound re-epithelialization 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.