Gene therapy in a new model of delayed wound healing

Research output: ThesisDoctoral Thesis (compilation)

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Abstract

Diabetes wounds result in significant morbidity, prolonged hospitalization and huge health care expenses.
As of yet, no optimal animal models of diabetic wound healing exist to study potential beneficial therapies.
Porcine wound healing is very similar to human wound healing. We stipulated that by inducing diabetes in
yorkshire pigs, wound healing would be delayed and exhibit abnormalities similar to those seen in human
diabetic wound healing. Furthermore we hypothesized that cell therapy and gene therapy may enhance epidermal
healing in this model of delayed wound healing.
In study one, we establish a delayed wound healing model in yorkshire pigs, mimicking diabetic
wound healing, by injecting streptozotocin intravenously. High serum glucose was established and wound
healing was considerably delayed and showed alterations in the intrinsic pathways.
In study two, transplantation of suspensions of fibroblasts or keratinocytes enhanced re-epithelialization
in this new model of delayed wound healing.
In study three, the beneficial effect of transplanting keratinocytes seen in study two was enhanced
by transfecting keratinocytes with a plasmid coding for IGF-1. Results showed a substantial over expression
of IGF-1 in the wound as well as improved epidermal healing in the treated group.
In study four, the beneficial effect of allogenic cells transfected with EGF was shown in healthy
non-diabetic pigs.
In study five, the beneficial effect of EGF seen in study four, was taken into account and autologous
keratinocytes transfected with EGF were transplanted into cutaneous wounds in our model of delayed
wound healing. Clear beneficial effects were demonstrated.
Collectively, we demonstrate a new model of delayed wound healing in the pig which mimicks
deficiencies seen in diabetic wounds. We were able to accelerate wound healing in this model by using cell
therapy and further improved it using gene therapy.
Original languageEnglish
QualificationDoctor
Awarding Institution
  • Surgery
Supervisors/Advisors
  • Svensson, Henry, Supervisor
  • Eriksson, Elof, Supervisor, External person
Award date2010 Oct 21
Publisher
ISBN (Print)978-91-86671-02-0
Publication statusPublished - 2010

Bibliographical note

Defence details

Date: 2010-10-21
Time: 13:00
Place: Medicinska klinikens Aula, Ingång 35, SUS, Malmö

External reviewer(s)

Name: Lindahl, Anders
Title: Professor
Affiliation: Göteborgs Universitet

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Subject classification (UKÄ)

  • Surgery

Free keywords

  • IGF-1
  • Gene therapy
  • Diabetes
  • Animal model
  • EGF

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