IGF-I gene transfer in thermally injured rats

M. G. Jeschke, R. E. Barrow, H. K. Hawkins, K. Yang, R. L. Hayes, B. J. Lichtenbelt, J. R. Perez-Polo, David Herndon

Research output: Contribution to journalArticle

63 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1015-1020
Number of pages6
JournalGene Therapy
Volume6
Issue number6
DOIs
StatePublished - Jun 1999

Fingerprint

Insulin-Like Growth Factor I
Liposomes
Galactosidases
Genes
Transfection
Lac Operon
Muscle Proteins
Complementary DNA
Hot Temperature
Body Weight
Wounds and Injuries
Wound Healing
Skin
Myofibroblasts
Granulation Tissue
Liver
Subcutaneous Injections
Radioimmunoassay
Sprague Dawley Rats
Cytoplasm

Keywords

  • Growth factor
  • Insulin-like growth factor-I
  • Liposomes
  • Trauma
  • Wound healing

ASJC Scopus subject areas

  • Genetics

Cite this

Jeschke, M. G., Barrow, R. E., Hawkins, H. K., Yang, K., Hayes, R. L., Lichtenbelt, B. J., ... Herndon, D. (1999). IGF-I gene transfer in thermally injured rats. Gene Therapy, 6(6), 1015-1020. https://doi.org/10.1038/sj.gt.3300923

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 journalArticle

Jeschke, MG, Barrow, RE, Hawkins, HK, Yang, K, Hayes, RL, Lichtenbelt, BJ, Perez-Polo, JR & Herndon, D 1999, 'IGF-I gene transfer in thermally injured rats', Gene Therapy, vol. 6, no. 6, pp. 1015-1020. https://doi.org/10.1038/sj.gt.3300923
Jeschke MG, Barrow RE, Hawkins HK, Yang K, Hayes RL, Lichtenbelt BJ et al. IGF-I gene transfer in thermally injured rats. Gene Therapy. 1999 Jun;6(6):1015-1020. https://doi.org/10.1038/sj.gt.3300923
Jeschke, M. G. ; Barrow, R. E. ; Hawkins, H. K. ; Yang, K. ; Hayes, R. L. ; Lichtenbelt, B. J. ; Perez-Polo, J. R. ; Herndon, David. / IGF-I gene transfer in thermally injured rats. In: Gene Therapy. 1999 ; Vol. 6, No. 6. pp. 1015-1020.
@article{d6feb634e4db453e97a2ba37d1bf12de,
title = "IGF-I gene transfer in thermally injured rats",
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.",
keywords = "Growth factor, Insulin-like growth factor-I, Liposomes, Trauma, Wound healing",
author = "Jeschke, {M. G.} and Barrow, {R. E.} and Hawkins, {H. K.} and K. Yang and Hayes, {R. L.} and Lichtenbelt, {B. J.} and Perez-Polo, {J. R.} and David Herndon",
year = "1999",
month = "6",
doi = "10.1038/sj.gt.3300923",
language = "English (US)",
volume = "6",
pages = "1015--1020",
journal = "Gene Therapy",
issn = "0969-7128",
publisher = "Nature Publishing Group",
number = "6",

}

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

VL - 6

SP - 1015

EP - 1020

JO - Gene Therapy

JF - Gene Therapy

SN - 0969-7128

IS - 6

ER -