FULL THICKNESS EPIDERM™, A DERMAL-EPIDERMAL SKIN MODEL TO STUDY EPITHELIAL-MESENCHYMAL INTERACTIONS.

It has long been recognized that significant paracrine signaling occurs between dermal fibroblasts and epidermal keratinocytes. Further, it is understood that such interactions likely modulate the response of skin to materials which may lead to contact irritant or allergic responses. Also, dermis related phenomena such as photo-aging and photo-damage, wound healing and cancer progression are ideally studied in a dermis-containing tissue. To address these issues, we have recently developed a second-generation skin model consisting of a fibroblast-containing dermal/keratinocyte-containing epidermal, full thickness tissue. In contradistinction to previous dermal/epidermal models, the new tissue 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 testing of potential allergens or irritants in that direct topical application is possible. Topical exposure to the common surfactant, 1% Triton X-100, results in MTT tissue viability dose response curves which fall within the normal range of the keratinocyte-only tissue, EpiDerm™. Currently, in order to produce a standardized, 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 100 µL of Triton X-100. The database average (184 tissue lots) is 6.74 ± 0.99 hours (± 1 standard deviation); initial lots of the full thickness tissue, tested in an identical manner, averaged 7.14 ± 1.33 hours (n=3). Histological cross-sections of the full thickness tissue show an epidermal layer which is very similar to EpiDerm and native epidermis atop a fibroblast-containing collagen matrix dermis-like layer. Based on these initial results, investigation of the tissue response to stimuli specifically affecting the dermis or epidermal/dermal “crosstalk” may prove rather informative. Note: Subsequent to submission of this abstract, additional data were obtained which have been included in this presentation.

Crosstalk, EpiDerm, EpiDerm-FT, EpiDermFT, Full thickness, Paracrine signaling, Photo-aging, Photo-damage, Wound healing