IGF-I gene transfer in thermally injured rats.
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.
Jeschke
M G
MG
Shriners Hospital for Children, University of Texas Medical Branch, Galveston, Texas 77550, USA.
Barrow
R E
RE
Hawkins
H K
HK
Yang
K
K
Hayes
R L
RL
Lichtenbelt
B J
BJ
Perez-Polo
J R
JR
Herndon
D N
DN
D000818:Animals; D002056:Burns / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008081:Liposomes; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014945:Wound Healing
D008081:Liposomes; D007334:Insulin-Like Growth Factor I