Subscribe to RSS
DOI: 10.1055/s-2002-19827
Gene Therapy, Electroporation, and the Future of Wound-Healing Therapies
Publication History
Publication Date:
29 January 2002 (online)
ABSTRACT
Chronic wounds are a major clinical problem with notable morbidity. Treatment is usually supportive and results in significant healthcare expenditures. It is estimated that 1.25 million people are burned each year in the United States and that 6.5 million have chronic skin ulcers caused by pressure, venous stasis, or diabetes mellitus.[1] Wound healing is a complex and lengthy process, often taking up to 12 months to complete. The cost of treating poorly healing foot wounds in the United States has been estimated at $1 billion per year.[2] A number of topical commercial products have become available to provide an optimal environment for problematic open wounds. Topical platelet-derived growth factor (PDGF)-BB has proven effective in improving healing in impaired wounds but has the disadvantage of requiring large and repeated doses. More recently, investigators have focused on the possibility of inserting genes encoding for growth factors such as PDGF-BB into the cells participating in the wound-healing response. This approach offers the potential of single-dose growth factor treatment of chronic wounds. There are several approaches for gene insertion, including viral vectors, gene guns, and electroporation. This article reviews the strategies and potential of these approaches, with a focus on electroporation.
KEYWORD
Gene therapy - electroporation - wound-healing therapies
REFERENCES
- 1 Singer A J, Clark R AF. Cutaneous wound healing. N Engl J Med . 1999; 341 738-746
- 2 Johnson & Johnson Web site (www.jnj.com). April 26, 2001 .
- 3 Donovan W E. Experimental models in skin flap research. In: Grabb WC, Myers MB, eds. Skin Flaps Boston: Little, Brown 1975: 40-72
- 4 Meyer W, Schwarz R, Neurand K. The skin of domestic mammals as a model for the human skin with specific reference to the domestic pig. Curr Prob Dermatol . 1978; 7 39-52
- 5 Shukla A, Rasik A M, Jain G K, Shankar R, Kulshrestha D K, Dhawan B N. In vitro and in vivo wound healing activity of asiaticoside isolated from centella asiatica. J Ethnopharmacol . 1999; 65 1-11
- 6 Simeon A, Monier F, Emonard H. Fibroblast-cytokine-extracellular matrix interactions in wound repair. Curr Top Pathol . 1999; 93 95-101
- 7 Clark R AF. Basics of cutaneous wound repair. J Dermatol Surg Oncol . 1993; 19 693-706
- 8 Montagna W, Yun J S. The skin of the domestic pig. J Invest Dermatol . 1964; 43 11
- 9 Clark R AF. Basics of cutaneous wound repair. J Dermatol Surg Oncol . 1993; 19 693-706
- 10 Hom D. Growth factors in wound healing. Otolaryngol Clin North Am . 1995; 28 933-953
- 11 Folkman J. Diagnostic and Therapeutic Applications of Angiogenesis Research. Paper presented at Symposium on Bone Growth; Portland: July 1993
- 12 Hayward P, Alison W, Carp P. Local infiltration of an angiogenic growth factor does not stimulate the delay phenomenon. Br J Plast Surg . 1991; 44 525-529
- 13 Lorenz H P, Hedrick M H, Chang J, Mehrara B J, Longaker M T. The impact of biomolecular medicine and tissue engineering on plastic surgery in the 21st century. Plast Reconst Surg . 2000; 105 2467-2481
- 14 Aston S J, Beasley R W, Thorne C N. Grabb and Smith's Plastic Surgery, 5th ed. Philadelphia: Lippincott-Raven 1997
- 15 Jyung R W, Mustoe T A, Busby W H, Clemmons D R. Increased wound-breaking strength induced by insulin-like growth factor I in combination with insulin-like growth factor binding protein-1. Surgery . 1994; 115 233-239
- 16 Yu W, Naim J O, Lanzafame R J. Expression of growth factors in early wound healing in rat skin. Lasers Surg Med . 1994; 15 281-289
- 17 Falanga V. Wound healing and chronic wounds. J Cutan Med Surg . 1998; 3 S1.1-S1.5
- 18 Partridge C. Influential factors in surgical wound healing. J Wound Care . 1998; 7 350-353
- 19 Quirinia A. Skin wound healing and ischaemia. Dan Med Bull . 1999; 46 85-105
- 20 Graham A. The use of growth factors in clinical practice. J Wound Care . 1998; 7 536-540
- 21 Hom D B, Simplot T C, Pernell K J, Manivel J C, Song C W. Vascular and epidermal effects of fibroblast growth factor on irradiated and nonirradiated skin flaps. Ann Otol Rhinol Laryngol . 2000; 109 667-675
- 22 Stone D, David A, Bolognani F, Lowenstein P R, Castro M G. Viral vectors for gene delivery and gene therapy within the endocrine system. J Endocrinol . 2000; 164 103-118
- 23 Liechty K W, Nesbit M, Herlyn M, Radu A, Adzick N S. Adenoviral-mediated overexpression of platelet-derived growth factor-B corrects ischemic impaired wound healing. J Invest Dermatol . 1999; 113 375-383
- 24 Fewell J G, MacLaughlin G, Mehta V, Gondo M, Nicol F, Wilson E, Smith L C. Gene therapy for the treatment of hemophilia B using PINC-formulated plasmid delivered to muscle with electroporation. Mol Ther . 2001; 3 574-583