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Effect of Multiple Gene Transfers of Insulinlike Growth Factor I Complementary DNA Gene Constructs in Rats After Thermal Injury
Marc G. Jeschke, MD;
Robert E. Barrow, PhD;
Hal K. Hawkins, MD;
Minas T. Chrysopoulo, MD;
J. Regino Perez-Polo, PhD;
David N. Herndon, MD
Arch Surg. 1999;134:1137-1141.
Hypothesis Multiple subcutaneous injections of cholesterol-containing cationic liposomes encapsulating the complementary DNA (cDNA) gene for insulinlike growth factor I (IGF-I) increase the rate of transfected skin cells and result in increased IGF-I protein levels in the skin with subsequent improvement in wound healing when compared with a single injection.
Setting Laboratory.
Intervention Twenty-four adult male Sprague-Dawley rats (350-375 g) received a full-thickness scald burn on 60% of their body surface. These rats were randomly divided to receive either 1 injection of liposomes containing 2.2 µg-cytomegalovirus-driven cDNA coding for IGF-I and 0.2 µg of the Lac Z gene cDNA construct, or 2 injections of liposomes containing 2.2 µg cytomegalovirus-driven cDNA coding for IGF-I and 0.2 µg of the Lac Z gene cDNA construct.
Main Outcome Measures Transfection rates and IGF-I protein levels in the skin and physiological responses to the IGF-I gene therapy, evaluated from changes in body weight, protein content in serum and liver, and the rate of burn wound healing.
Results There was a significant decrease in transfection rate and IGF-I protein expression distal from the injection site in animals receiving 1 injection, as compared with a consistent increase in rats receiving multiple injections. Multiple injections improved the response to thermal trauma by increasing the extent of the healed burn wound 33 days after thermal injury (single injection, 31%±1% vs multiple injections, 38%±2%), total serum protein (single injection, 52±0.5 g/L vs multiple injections, 55±0.6 g/L), and total liver protein (single injection, 82.0±0.3 mg/mL vs multiple injections, 91.0±3.8 mg/mL), P<.05.
Conclusions Gene transfer rates can be increased by multiple injections of liposomes encapsulating IGF-I cDNA constructs. Increased transfer results in greater IGF-I protein skin concentrations, accelerated wound healing, and increased serum and liver protein concentrations. The clinical relevance of these findings is that liposomal gene constructs should be applied in well-defined distances to improve gene transfer in the skin, and thus clinical outcome after thermal injury.
From the Shriners Hospital for Children, Galveston, Tex (Dr Barrow); and the Departments of Surgery (Drs Jeschke, Barrow, Hawkins, Chrysopoulo, and Herndon) and Human Biological Chemistry and Genetics (Dr Perez-Polo), University of Texas Medical Branch, Galveston.
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Epidermal Homeostasis: The Role of the Growth Hormone and Insulin-Like Growth Factor Systems
Edmondson et al.
Endocr. Rev. 2003;24:737-764.
ABSTRACT
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