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 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.
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Acknowledgements
This study was supported by the Clayton Foundation for Research and the Shriners Hospital for Children. We would like to thank Anne S Burke, Robert A Cox, Drs Minas Chrysopoulo and Meelie DebRoy for their technical support.
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Jeschke, M., Barrow, R., Hawkins, H. et al. IGF-I gene transfer in thermally injured rats. Gene Ther 6, 1015–1020 (1999). https://doi.org/10.1038/sj.gt.3300923
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DOI: https://doi.org/10.1038/sj.gt.3300923
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