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 reepithelialization 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1015-1020 |
| Number of pages | 6 |
| Journal | Gene Therapy |
| Volume | 6 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 1999 |
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Keywords
- Growth factor
- Insulin-like growth factor-I
- Liposomes
- Trauma
- Wound healing
ASJC Scopus subject areas
- Genetics
Cite this
IGF-I gene transfer in thermally injured rats. / Jeschke, M. G.; Barrow, R. E.; Hawkins, H. K.; Yang, K.; Hayes, R. L.; Lichtenbelt, B. J.; Perez-Polo, J. R.; Herndon, David.
In: Gene Therapy, Vol. 6, No. 6, 06.1999, p. 1015-1020.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - IGF-I gene transfer in thermally injured rats
AU - Jeschke, M. G.
AU - Barrow, R. E.
AU - Hawkins, H. K.
AU - Yang, K.
AU - Hayes, R. L.
AU - Lichtenbelt, B. J.
AU - Perez-Polo, J. R.
AU - Herndon, David
PY - 1999/6
Y1 - 1999/6
N2 - 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 reepithelialization 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.
AB - 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 reepithelialization 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.
KW - Growth factor
KW - Insulin-like growth factor-I
KW - Liposomes
KW - Trauma
KW - Wound healing
UR - http://www.scopus.com/inward/record.url?scp=0033058945&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033058945&partnerID=8YFLogxK
U2 - 10.1038/sj.gt.3300923
DO - 10.1038/sj.gt.3300923
M3 - Article
C2 - 10455403
AN - SCOPUS:0033058945
VL - 6
SP - 1015
EP - 1020
JO - Gene Therapy
JF - Gene Therapy
SN - 0969-7128
IS - 6
ER -