Team:Jefferson VA SciCOS/Project

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Title

The Production of FGF in Response to Near-Anoxic Oxygen Thresholds

Abstract

The amount of oxygenation at ulcer sites is a key determinant of the outcome of healing because oxygen is crucial to the healing process and for resistance to infection. The non-healing skin ulcers that are formed from diabetic gangrene tend to be hypoxic; hypoxia is a condition not favorable to tissue repair. According to numerous studies, topical treatments of growth factors and peripheral blood mononuclear cells can help treat ulcers non-invasively in gangrene patients. It is posited that the growth factors promote angiogenesis, the physiological process by which new blood vessels form from pre-existing vessels. It is also a vital process in growth and development as well as in repair of damaged tissue. Furthermore, angiogenesis can render greater oxygen delivery to wounded areas, further enhancing growth and recovery to the areas suffering from chronic ischemia. In order to promote angiogenesis in gangrenous sites, and in turn treat the ulcers, growth factors such as fibroblast growth factor (FGF), vascular endothelial growth factor (VGF), and keratinocyte growth factor (KGF) can be produced in elevated quantities. To address the issue of inadequate oxygen levels during the healing process, we coupled the VHb gene promoter, which encodes for the Vitreoscilla hemoglobin molecule, to a downstream gene encoding KGF. The VHb promoter is most activated at an oxygen threshold of 2%, allowing for maximum transcription of the KGF gene and production of the growth factor in response to conditions of hypoxia. We also wanted to tested the production of another essential growth factor, FGF, under the influence of various constitutive promoters. This oxygen-sensing device is part of an array of growing applications targeted towards the promotion of angiogenesis as a means of healing in patients with severe, diabetic gangrene.

         Wound

      Angiogenesis

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 '''''Abstract'''
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-The amount of wound oxygenation is a key determinant of the outcome of healing because oxygen is crucial to the healing process and for resistance to infection. Chronic ischemic wounds tend to be hypoxic, and near-anoxic hypoxia is not favorable to tissue repair. Angiogenesis, the physiological process by which new blood vessels form from pre-existing vessels, is a vital process in growth and development as well as in repair of damaged tissue. Furthermore, angiogenesis can render greater oxygen delivery to wounded areas, further enhancing growth and recovery. In order to promote angiogenesis in chronic wounds, growth factors such as fibroblast growth factor (FGF), vascular endothelial growth factor (VGF), and keratinocyte growth factor (KGF) can be produced in elevated quantities. To address the issue of inadequate oxygen levels during the wound healing process, we coupled the VHb gene promoter, which encodes for the Vitreoscilla hemoglobin molecule, to a downstream gene encoding FGF. The VHb promoter is activated at an oxygen threshold below 2%, allowing for transcription of the FGF gene and production of the growth factor in response to conditions of near-anoxia. We also tested the production of another essential growth factor, KGF, under the influence of various constitutive promoters. This oxygen-sensing device is part of an array of growing applications targeted towards the promotion of angiogenesis as a means of wound healing in patients with severe, untreatable wounds.
+The amount of oxygenation at ulcer sites is a key determinant of the outcome of healing because oxygen is crucial to the healing process and for resistance to infection. The non-healing skin ulcers that are formed from diabetic gangrene tend to be hypoxic; hypoxia is a condition not favorable to tissue repair. According to numerous studies, topical treatments of growth factors and peripheral blood mononuclear cells can help treat ulcers non-invasively in gangrene patients. It is posited that the growth factors promote angiogenesis, the physiological process by which new blood vessels form from pre-existing vessels. It is also a vital process in growth and development as well as in repair of damaged tissue. Furthermore, angiogenesis can render greater oxygen delivery to wounded areas, further enhancing growth and recovery to the areas suffering from chronic ischemia. In order to promote angiogenesis in gangrenous sites, and in turn treat the ulcers, growth factors such as fibroblast growth factor (FGF), vascular endothelial growth factor (VGF), and keratinocyte growth factor (KGF) can be produced in elevated quantities. To address the issue of inadequate oxygen levels during the healing process, we coupled the VHb gene promoter, which encodes for the Vitreoscilla hemoglobin molecule, to a downstream gene encoding KGF. The VHb promoter is most activated at an oxygen threshold of 2%, allowing for maximum transcription of the KGF gene and production of the growth factor in response to conditions of hypoxia. We also wanted to tested the production of another essential growth factor, FGF, under the influence of various constitutive promoters. This oxygen-sensing device is part of an array of growing applications targeted towards the promotion of angiogenesis as a means of healing in patients with severe, diabetic gangrene.
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