Effect of Hyperbaric Oxygen and Growth Factors on Rabbit Ear Ischemic Ulcers

Zhao, Lily; Davidson, John D.; Wee, Sang Chin; Roth, Sanford I.; Mustoe, Thomas A.

doi:10.1001/archsurg.1994.01420340057010

Cited by 144 publications

(108 citation statements)

References 19 publications

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“…Advances in the understanding of neovascularization have made the process of angiogenesis and angiogenic factor expression prime targets for therapeutic manipulation in wound healing (26,37). Efforts have been made to induce or stimulate new blood vessel formation to reduce the unfavourable tissue effects caused by local ischaemia, or to enhance tissue repair (38). Gene therapy in this environment poses a particular challenge (39).…”

Section: Discussionmentioning

confidence: 99%

Abrogation of TGF-β by antisense oligonucleotides modulates expression of VEGF and increases angiogenic potential in isolated fibroblasts from radiated skin

Riedel¹

1998

Int J Mol Med

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Abstract.The transforming growth factor-ß (TGF-ß) has been identified as an important component of wound healing. Recent developments in molecular therapy offer good prospects for the modulation of wound healing, specifically those targeting TGF-ß. The aim of this study was to analyze the effect of TGF-ß targeting on the expression of angiogenic vascular endothelial growth factor (VEGF), a key regulator of angiogenesis and in vitro angiogenic activity in fibroblasts isolated from radiation-induced chronic dermal wounds. The expression of angiogenic VEGF in tissue samples from radiation-induced chronic dermal wounds was investigated by immunohistochemistry and microarray technique. The effect of TGF-ß targeting using antisense oligonucleotides on the expression of VEGF in isolated fibroblasts was analyzed by ELISA and multiplex RT-PCR. Human endothelial cells (ECs) were grown in conditioned medium produced from the treated fibroblasts. EC migration was measured using a modified Boyden chamber; EC tube formation was analyzed under a light microscope. Immunohistochemical investigation and microarray analysis demonstrated a decreased expression of VEGF protein and mRNA in tissue samples from radiationinduced chronic dermal wounds compared to normal human skin. Antisense TGF-ß oligonucleotide treatment significantly up-regulated VEGF secretion in vitro. Addition of conditioned medium from TGF-ß antisense-treated fibroblasts resulted in an increase in EC cell migration and tube formation. In conclusion, our results demonstrate that TGF-ß antisense oligonucleotide technology may be a potential therapeutic option for stimulation of angiogenesis in radiation-induced dermal wounds.

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Section: Discussionmentioning

confidence: 99%

Abrogation of TGF-β by antisense oligonucleotides modulates expression of VEGF and increases angiogenic potential in isolated fibroblasts from radiated skin

Riedel¹

1998

Int J Mol Med

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“…Experimentally there is a benefit to hyperbaric oxygen therapy (HBO) in a clinically relevant ischemic rabbit ear ulcer model [42], particularly when given for a duration equivalent to clinical protocols [32]. In a clinical study periwound-tissue oxygen tension measured during HBO correlated directly with the improvement in wound healing of chronic wounds: during HBO treatment of patients with chronic leg wounds, the oxygen tensions of their wounds were measured and further compared to the wound healing rate.…”

Section: Impact Of Hyperoxia On Wound Healingmentioning

confidence: 99%

“…Recombinant growth factors (r-TGF-␤1, r-PDGF-BB) increase wound healing in ischemic rabbit ear ulcers by 200%, but still only 40% of normal at 7 days. If growth factors are applied together with HBO, the negative effect of ischemia on wound healing is completely reversed [42]. However, under conditions of 20 treatments with HBO (rather than five [42]), the effects of HBO are much greater, and no additional benefit is seen from the addition of growth factor (TGF-␤3) [32].…”

Section: Hbo and Recombinant Growth Factorsmentioning

confidence: 99%

Oxygen in wound healing: More than a nutrient

Davidson

Mustoe

2001

Wound Repair Regeneration

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Abstract. This article provides an overview of the role of oxygen in wound healing. The understanding of this role has undergone a major evolution from its long-recognized importance as an essential factor for oxidative metabolism, to its recognition as an important cell signal interacting with growth factors and other signals to regulate signal transduction pathways. Our laboratory has been engaged in thestudy of animal models of skin ischemia to explore in vivo the impact of hypoxia as well as the use of oxygen as a therapeutic agent either alone or in combination with other agents such as growth factors. We have demonstrated a synergistic effect of systemic hyperbaric oxygen and growth factors that has been substantiated by Hunt's group. Within the past 10 years research in the field of wound healing has given new insight into the mechanism of action of hypoxia and hyperoxia as modifiers of the normal time-course of wound healing. The article concludes with a discussion of why hypoxia and hyperoxia intercurrently play an important role in wound healing. Hypoxia-inducible factor 1 is crucial in that interplay.

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“…Moreover, several animal studies have demonstrated that chronic hypoxia results in decreased granulation tissue production and delayed onset of re-epithelialization. 106,107 In 1985 Clyne et al reported that the diffusion of oxygen in lipodermatosclerotic or ulcerated gaiter area skin was lower than in the skin of subjects without significant disease. 108 Since it had also been proposed that pericapillary fibrin deposits might be a potential causative factor in limiting oxygen diffusion, thus contributing to tissue necrosis and ulceration, 15 Stacey et al conducted a critical study, which showed that such deposits preceded observable lipodermatosclerotic skin alterations and importantly tissue hypoxia.…”

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confidence: 99%