Characterisation of a human skin equivalent model to study the effects of ultraviolet B radiation on keratinocytes

Fernandez, Tara L., Van Lonkhuyzen, Derek R., Dawson, Rebecca A., Kimlin, Michael G., & Upton, Zee (2014) Characterisation of a human skin equivalent model to study the effects of ultraviolet B radiation on keratinocytes. Tissue Engineering Part C: Methods, 20(7), pp. 588-598.

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Abstract

The incidences of skin cancers resulting from chronic ultraviolet radiation (UVR) exposure are on the incline both in Australia and globally. Hence, the cellular and molecular pathways associated with UVR-induced photocarcinogenesis urgently need to be elucidated, in order to develop more robust preventative and treatment strategies against skin cancers. In vitro investigations into the effects of UVR (in particular the highly-mutagenic UVB wavelength) have, to date, mainly involved the use of cell culture and animal models. However, these models possess biological disparities to native skin, which to some extent have limited their relevance to the in vivo situation. To address this, we characterised a 3-dimensional, tissue-engineered human skin equivalent (HSE) model (consisting of primary human keratinocytes cultured on a dermal-derived scaffold) as a representation of a more physiologically-relevant platform to study keratinocyte responses to UVB. Significantly, we demonstrate that this model retains several important epidermal properties of native skin. Moreover, UVB-irradiation of the HSE constructs was shown to induce key markers of photodamage in the HSE keratinocytes, including the formation of cyclobutane pyrimidine dimers, the activation of apoptotic pathways, the accumulation of p53 and the secretion of inflammatory cytokines. Importantly, we also demonstrate that the UVB-exposed HSE constructs retain the capacity for epidermal repair and regeneration following photodamage. Together, our results demonstrate the potential of this skin equivalent model as a tool to study various aspects of the acute responses of human keratinocytes to UVB radiation damage.

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4 citations in Scopus
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2 citations in Web of Science®

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ID Code: 65828
Item Type: Journal Article
Refereed: Yes
Keywords: Ultraviolet radiation, Skin cancer, Tissue-engineered HSE
DOI: 10.1089/ten.TEC.2013.0293
ISSN: 2152-4955
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > PUBLIC HEALTH AND HEALTH SERVICES (111700)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Current > Schools > School of Public Health & Social Work
Copyright Owner: Copyright 2013 Mary Ann Liebert, Inc.
Copyright Statement: This is a copy of an article published in Tissue Engineering Part C: Methods, 20(7) © 2014 [copyright Mary Ann Liebert, Inc.]; Tissue Engineering Part C: Methods is available online at: http://online.liebertpub.com.
Deposited On: 09 Jan 2014 02:50
Last Modified: 14 Sep 2014 19:58

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