Development of a 3D co-culture system to assess the respiratory sensitizing potential of chemicals

August 20, 2017

A. Chary 1,2, T. Serchi1, J. Hennen2, B. Bloemeke2, J. Ezendam3, S. Cambier1, E. Moschini1, A.C. Gutleb1
1Department of Environmental Research and Innovation (ERIN), Luxembourg Institute of Science and Technology (LIST), Belvaux, Luxembourg,
2Department of Environmental Toxicology, University of Trier, Trier, Germany,
3RIVM Centre for Environmental Protection (GZB), National Institute for Public Health and the Environment (RIVM), Utrecht, The Netherlands.

The aim of this study is to adapt the 3D-co-culture system previously developed by LIST (Klein et al.1,2) to allow the in vitro study of respiratory sensitization processes and to
find markers for the assessment of the respiratory sensitizing potential of inhaled compounds and mimicking the alveolar barrier to study cell-to-cell communication and inflammatory effects of nano particles at the air-liquid-interface.

– Chemical respiratory sensitization resulting from occupational exposure to synthetic compounds has increased over the last decades leading to important occupational health issues.
– Complex in vitro co-culture systems represent valuable tools to understand the mechanisms involved in lung sensitization.
– No validated in vitro model is currently available to assess the respiratory sensitization potential of chemicals.
– An in vitro model developed by Klein et al.1,2 combining alveolar type II epithelial cell line A549, acute monocyte cell line THP-1 cells differentiated into macrophage like cells, endothelial cells EA.hy 926 and human mast cell line HMC-1 in co-culture has been developed to assess the toxic effects of particles at the alveolar barrier. The co-culture was designed in a 3D-organisation to mimic at best the in vivo histology of the alveolar barrier and cultured at the air liquid interface (ALI) to mimic realistic exposure of inhaled compounds.
– DCs, which have a crucial role in sensitization, need indeed to be included in such model to study the relevant process of sensitization. The co-culture was redesigned to address the sensitizing potential of inhaled compounds in a relevant way, including the possibility of migration of DCs to ensure to have a functional model.

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