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MODELLING THE HUMAN BRONCHI AND ITS RESPONSES IN VITRO.
Greenwell, L., Carthew, P., Westmoreland, C., and Fentem, J.
Safety and Enviornmental Assurance Centre, Unilever Colworth, Sharnobrook, Bedford, U.K.
Presented at 5th World Congress, Berlin, Germany, August, (2005).
Keywords: 3R’s, 7th Amendment, Air liquid interface cultures, Bronchial tissue, Ciliogenesis, EU cosmetic directive, Efficacy, EpiAirway, EpiAirway-100, Human Bronchi, Inhalation toxicology, MTT, No observed adverse effect level (NOAEL), Protein exudation, Respiratory toxins, TEER, Toxicological tool, Tracheo-bronchial
Endpoints: MTT, Protein Release, TEER
Materials Tested: 4-Ipomeanol, Acrolein, Paraquat, Respiratory toxins
Summary: Technological developments in cell culture techniques have lead to the production of increasingly organotypic organ cultures. MatTek currently produce 3-dimensional, multi-differentiated of a variety of organs, including the human bronchi. The EpiAirway™ bronchial cultures not only present an organotypic phenotype, but also provide the opportunity for representative aerosol exposure as they are grown at the air:liquid interface. These are currently utilised for a variety of purposes, but the aim of this study was to investigate their efficacy as a toxicological tool.
EpiAirway cultures were exposed to a range of known respiratory toxins and a variety of their responses assessed. These included TEER, MTT, protein exudation, histopathology and cytokine analysis. From this a toxicological response profile was created and compared previous studies into alternative lung models. Morphological analysis showed that the cultures were representative of bronchial epithelium, and that damage occurred indiscriminately across cell types. Biochemical results showed immediate, transient release of pro-inflammatory cytokines concurrent with a similarly transient loss of TEER. This was followed by dose-dependent change in TEER and a dose- and time-dependant decrease of cellular viability. The toxicological profile was significantly attenuated following co-exposure to antioxidant-rich, surrogate, epithelial lining fluid (sELF).
Overall, the EpiAirway cultures displayed significant morphological and biochemical correlation with both in vitro and in vivo models, including primary Type II cell monocultures (Richards et al., 1990). This Unilever study has served to iterate the potential value of EpiAirway air-liquid interface cultures in modelling the human respiratory tract in vitro.
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