383. MODELLING THE HUMAN BRONCHI AND ITS RESPONSES IN VITRO.

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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).

Summary:
This study by researchers at Unilever’s Safety and Environment Assurance Centre (SEAC) demonstrated that MatTek’s EpiAirway in vitro human tracheal/bronchial tissue equivalent displayed significant morphological and biochemical correlation with both in vitro and in vivo models, re-confirming the potential value of EpiAirway air-liquid interface tissues in modeling the human respiratory tract in vitro.

Technological developments in cell culture techniques have led to the production of increasingly organotypic organ cultures. MatTek currently produces 3-dimensional, multi-differentiated (tissues) 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 (tissues) 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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EpiAirway Data Sheet

EpiAirway Specifications

EpiAirway Technical References

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Applications: 7th Amendment Cosmetics Directive, Airway research, Inhalation toxicology, Validation - in vitro tissue models

Keywords: 3R’s, 7th Amendment to the Cosmetics Directive, 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

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