IGF-I gene transfer in thermally injured rats

Exogenous insulin-like growth factor-I (IGF-I) is known to improve the path ophysiology of a thermal injury, however, deleterious side-effects have lim ited its utility. Cholesterol;containing cationic liposomes that encapsulat e complementary DNA (cDNA) are nonviral carriers used for in vivo gene tran sfection. We propose that liposome IGF-I gene transfer will accelerate woun d healing in burned rats and attenuate deleterious side-effects associated with high levels of IGF-I. To test this hypothesis IGF-I gene constructs, e ncapsulated 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 wee kly subcutaneous injections of liposomes plus the lacZ gene coding for beta -galactosidase, liposomes plus cDNA for IGF-I and beta-galactosidase or lip osomes plus the rhIGF-I protein. Body weights and wound healing were measur ed. Muscle and liver dry/wet weights and IGF-I concentrations in serum, ski n and liver were measured by radioimmunoassay. Transfection was confirmed b y histochemical staining for beta-galactosidase. Rats receiving the IGF-I c DNA constructs exhibited the most rapid wound re-epithelialization and grea test increase in body weight and gastrocnemius muscle protein content (P < 0.05). Local IGF-I protein concentrations in the skin were higher when comp ared to liposomes containing only the lacZ gene (P < 0.05) Transfection was apparent in the cytoplasm of myofibroblasts, endothelial cells and macroph ages of the granulation tissue. Liposomes containing the IGF-I gene constru cts proved effective in preventing muscle protein wasting and preserving to tal body weight after a severe thermal injury.