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IGF-I gene transfer in thermally injured rats

Gene Therapy volume 6, pages 1015–1020 (1999)Cite this article

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 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.

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References

  1. Firedmann T . Overcoming the obstacles to gene therapy Sci Am 1997 6: 96–101

    Google Scholar 

  2. Felgner PL . Nonviral strategies for gene therapy Sci Am 1997 6: 102–106

    Article  Google Scholar 

  3. Felgner PL, Tsai YL, Sukhu L . Improved cationic lipid formulations for in vivo gene therapy Ann NY Acad Sci 1995 772: 126–139

    Article  CAS  Google Scholar 

  4. Felgner PL . Improvements in cationic liposomes for in vivo gene transfer Hum Gene Ther 1996 7: 1791–1793

    Article  CAS  Google Scholar 

  5. Bangham AD . Physical structure and behavior of lipids and lipid enzymes Adv Lipid Res 1963 1: 65–104

    Article  CAS  Google Scholar 

  6. Sharata HH, Katz KH . Liposomes Int J Dermatol 1996 35: 761–769

    Article  CAS  Google Scholar 

  7. Wheeler CJ, Felgner PL, Tsai YT . A novel cationic lipid greatly enhances plasmid DNA delivery and expression in mouse lung Proc Natl Acad Sci USA 1996 93: 11454–11459

    Article  CAS  Google Scholar 

  8. Pierre E, Herndon DN, Barrow RE . Growth hormone therapy in the treatment of burns In: Torosian MH (ed) . Growth Hormone in Critical Illness: Research and Clinical Studies RG Landes Co: Texas 1996 pp 105–116

    Google Scholar 

  9. Meyer NA, Barrow RE, Herndon DN . Combined insulin-like growth factor-1 and growth hormone improves weight loss and wound healing in burned rats J Trauma 1996 31: 1008–1012

    Article  Google Scholar 

  10. Huang KF, Chung DH, Herndon DN . Insulin-like growth factor-1 (IGF-I) reduces gut atrophy and bacterial translocation after severe burn injury Arch Surg 1993 128: 47–54

    Article  CAS  Google Scholar 

  11. Strock LL, Singh H, Abdullah A . The effect of insulin-like growth factor-1 on postburn hypermetabolism Surgery 1990 108: 161–164

    CAS  PubMed  Google Scholar 

  12. Clemmons DR . Insulin-like growth factor-1 as an anabolic agent in catabolic states Ann Intern Med 1994 120: 596–597

    Google Scholar 

  13. Lo HC, Hinton PH, Peterson CA, Ney DM . Simultaneous treatment with IGF-I and GH additively increases anabolism in parenterally fed rats Am J Physiol 1995 269: E368–E376

    CAS  PubMed  Google Scholar 

  14. Zaizen Y, Ford EG, Costin G . The effect of perioperative exogenous growth hormone on wound bursting strength in normal and malnourished rats J Ped Surg 1990 25: 70–74

    Article  CAS  Google Scholar 

  15. Guler HP, Zapf J, Scheiwiller E, Froesch ER . Recombinant human insulin-like growth factor-1 stimulates growth and has distinct effects on organ size in hypophysectomized rats Proc Natl Acad Sci USA 1988 85: 4889–4893

    Article  CAS  Google Scholar 

  16. Walker JL, Ginalska-Malinowska G, Romer TE . Effects of the infusion of insulin-like growth factor-1 in a child with growth hormone insensitivity syndrome New Engl J Med 1991 324: 1483–1488

    Article  CAS  Google Scholar 

  17. Martin P . Wound healing-aiming for perfect skin regeneration Science 1997 276: 75–81

    Article  CAS  Google Scholar 

  18. Pierre EJ, Perez-Polo JR, Mitchell AT, Herndon DN . Insulin-like growth factor-1 liposomal gene transfer and systemic growth hormone stimulate wound healing J Burn Care Rehab 1997 18: 287–291

    Article  CAS  Google Scholar 

  19. Jabri N et al. Adverse effects of recombinant human insulin-like growth factor-I in obese insulin-resistant type II diabetic patients Diabetes 1994 43: 369–374

    Article  CAS  Google Scholar 

  20. Bondy CA et al. Clinical uses of insulin-like growth factor-I Ann Intern Med 1994 120: 593–601

    Article  CAS  Google Scholar 

  21. Gore DC et al. Effect of exogenous growth hormone on whole-body and isolated-limb protein kinetics in burned patients Arch Surg 1991 126: 38–43

    Article  CAS  Google Scholar 

  22. Herndon DN, Barrow RE, Kunkel KR, Rutan RL . Effects of recombinant human growth hormone on donor-site healing in severely burned children Ann Surg 1990 212: 424–431

    Article  CAS  Google Scholar 

  23. Steenfos HH . Growth factors and wound healing Scand J Plast Reconstr Hand Surg 1994 28: 95–105

    Article  CAS  Google Scholar 

  24. Alexander MY, Akhurst RJ . Liposome-mediated gene transfer and expresion via the skin Hum Mol Genet 1995 4: 2279–2285

    Article  CAS  Google Scholar 

  25. Herndon DN, Barrow RE, Rutan RL . A comparison of conservative versus early excision Ann Surg 1989 209: 547–553

    Article  CAS  Google Scholar 

  26. Rodriguez JL, Miller CG, Garner WL . Correlation of the local and systemic cytokine response with clinical outcome following thermal injury J Trauma 1993 34: 684–694

    Article  CAS  Google Scholar 

  27. Herndon DN, Wilmore DW, Mason AD Jr, Pruitt BA Jr . Development and analysis of a small animal model stimulating the human postburn hypermetabolic response J Surg Res 1978 25: 394–403

    Article  CAS  Google Scholar 

  28. Yang K, Perez-Polo JR, Faustinella G . In vitro studies of liposome-mediated gene transfection. In: Perez-Polo JR (ed) . Paradigms of Neural Injury; Methods of Neuroscience Academic Press 1996 290–297

    Google Scholar 

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Acknowledgements

This study was supported by the Clayton Foundation for Research and the Shriners Hospital for Children. We would like to thank Anne S Burke, Robert A Cox, Drs Minas Chrysopoulo and Meelie DebRoy for their technical support.

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Authors and Affiliations

  1. Shriners Hospital for Children, University of Texas Medical Branch, Galveston, Texas, USA

    M G Jeschke, R E Barrow, H K Hawkins, B J Lichtenbelt & D N Herndon

  2. Shriners Hospital for Children Department of Surgery, University of Texas Medical Branch, Galveston, Texas, USA

    M G Jeschke, R E Barrow, H K Hawkins, B J Lichtenbelt & D N Herndon

  3. Shriners Hospital for Children Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, Texas, USA

    J R Perez-Polo

  4. Department of Neurosurgery, University of Texas Medical School, Houston, Texas, USA

    K Yang & R L Hayes

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  1. M G Jeschke
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Jeschke, M., Barrow, R., Hawkins, H. et al. IGF-I gene transfer in thermally injured rats. Gene Ther 6, 1015–1020 (1999). https://doi.org/10.1038/sj.gt.3300923

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