Epidermal adhesion molecules in human wounds and development of a tissue explant culture system to investigate modification of their expression
Jones, William Dylan
mesheuropmc: integumentary system
When cutaneous injury involves disruption of the basement membrane, keratinocytes must disassemble their complex attachment to it, enabling lateral migration over a wound surface consisting of a new provisional matrix. Integrin cell adhesion molecules have already been characterised as prime mediators of this process in experimental human wounds. However, very little is known about the role played by integrins as well as other epidermal adhesion molecules such as syndecans in more complex chronic wounds. In this study, a human model of rapidly healing surgically induced wounds and pilonidal excision wound tissue was used to establish the previously documented expression of epidermal adhesion molecules in the acute healing process. Chronic venous leg ulcer wound tissue was then taken as representing the process of chronic wounding and used to investigate its effect on these adhesion molecules. Differences were found between the expression of adhesion molecules in acute and chronic wounds. In particular as pi expression was decreased in chronic wound epidermis. As a result, a tissue explant culture system was developed to investigate the possibility of modifying its expression on chronic wound keratinocytes. Characterisation of venous leg ulcer explant tissue within this system highlighted the inherent heterogeneity of the tissue, leading to a large degree of variability in the levels of analytes such as IL-8 measured within it. Pilot experiments with two biopsies suggested that aspi expression could be up regulated on chronic wound keratinocytes in response to an inflammatory stimulus. However, further development of this system will be required to reduce the variability within it, before real changes in cell behaviour in response to exogenous stimuli can be demonstrated. Given the difficulties in extrapolating data from animal to human tissue, development of models such as this could prove invaluable in trying to understand the complexities of chronic wounds.
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