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Alternatives to Laboratory Animals - ATLA

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Full Thickness EpiDerm™: a Dermal–Epidermal Skin Model to Study Epithelial–Mesenchymal Interactions

Joseph Kubilus, Patrick J. Hayden, Seyoum Ayehunie, Sarah D.K. Lamore, Cynthia Servattalab, Kristen L. Bellavance, John E. Sheasgreen and Mitchell Klausner

Unlike previous dermal–epidermal models, Full Thickness EpiDerm™ is cultured in an easily manipulated cell culture insert, and the tissue extends from wall to wall. In terms of ease of use, these characteristics greatly facilitate the testing of potential allergens or irritants in that direct topical application is possible. Topical exposure to the common surfactant, 1% Triton X-100, resulted in MTT tissue viability dose–response curves that fell within the normal range of the keratinocyte-only tissue, EpiDerm. Currently, in order to produce a standardised, reproducible organotypic tissue, all lots of EpiDerm are compared to a reference database of effective time-50 (ET-50) values, i.e. the time of exposure after which viability is reduced to 50% following exposure to 100μl of Triton X-100. The database average (184 tissue lots) is 6.74 ± 0.99 hours (± 1 SD); initial lots of the full thickness tissue, tested in an identical manner, averaged 7.79 ± 1.24 hours (n = 11). Histological cross-sections of the full thickness tissue showed an epidermal layer that is very similar to EpiDerm and native epidermis on a fibroblast-containing collagen matrix dermis-like layer. Irradiation of the tissue with ultraviolet light induced an increase in collagenase (MMP-1) release. Based on these initial results, investigation of the tissue response to stimuli specifically affecting the dermis or epidermal/dermal “cross-talk” will probably prove informative.