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VEGF gene therapy and therapeutic angiogenesis in plastic surgery

Mackenzie, Duncan Neil; (2003) VEGF gene therapy and therapeutic angiogenesis in plastic surgery. Doctoral thesis (M.D), UCL (University College London). Green open access

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Abstract

Background: The limits of flaps used in reconstructive plastic surgery depend on their blood supplies. Flap failure or partial necrosis is inevitable if these limits are exceeded. VEGF is a potent angiogenic cytokine that has been the subject of much investigation concerning its ability to stimulate the growth of vascular networks. It has been shown to improve circulation to ischaemic limbs and ischaemic myocardium. There have also been some recent positive findings in plastic surgery research. Researchers have used both recombinant protein and plasmid DNA coding for the cytokine. Hypothesis: That VEGF gene or cytokine therapy could be used to enhance the survival of a pedicled skin flap in which there was an ischaemic random extension. Methods: Four fibroblast cell lines were prepared expressing each of VEGFA165, VEGFB167 and VEGFB186 and a control plasmid, GFP (green fluorescent protein). These were administered intra-operatively to rat abdominal island skin flaps, along with saline controls. At seven days, the flaps were assessed for percentage of flap survival and angiographic and histological evidence of angiogenesis. Other therapeutic agents tested on this model were VEGFB167 plasmid DNA delivered to the flap using a gene gun and VEGFA165, VEGFB167 and bFGF cytokines. The results were assessed in the same way. Results: The survival of flaps treated with VEGFA165- and VEGFB167-expressing cells was significantly better than those treated with saline (p=<0.05). Angiograms did not show any significant differences between treatment and controls. Assessment of histological specimens showed qualitative differences between VEGFB167-treated flaps and controls. The gene gun-delivered VEGFB plasmid and the cytokines did not augment survival of the skin flaps. Conclusion: Ischaemic skin flap survival can be enhanced by administration of cells secreting VEGF. Angiogenesis is likely to be the mechanism of this effect. This technique may lead to further advances in flap design.

Type: Thesis (Doctoral)
Qualification: M.D
Title: VEGF gene therapy and therapeutic angiogenesis in plastic surgery
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
URI: https://discovery.ucl.ac.uk/id/eprint/10116678
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