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Advances in in vitro models to study pulmonary toxicity of particles, chemicals and pharmaceuticals

Programme of the Session

  • 10:00 – 10:15 CE course opening and introduction
  • 10:15 – 11:00 Human airway epithelial models: an introduction and their applicability in mechanistic research and regulatory toxicology 
    Patrick Hayden
    MatTek Corporation, USA
  • 11:00 – 11:45 Organic cation transporter function in different in vitro lung epithelial models: impact on delivery of pharmaceuticals and chemicals
    Carsten Ehrhardt
    School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Ireland
  • 11:45 – 12:00 Discussion
  • 12:00 – 13:00 Lunch
  • 13:00 – 13:45 Progress and future perspectives of in vitro airway models to study translocation and pulmonary immunotoxicity of nanoparticles
    Hedwig Braakhuis
    RIVM, the Netherlands
  • 13:45 – 14:30 Ex vivo lung models as a tool to study respiratory injury and inflammation  
    Katherina Sewald
    Fraunhofer-Institute for Toxicology and Experimental Medicine, Hannover, Germany
  • 14:30 – 15:15 3D models of the lung for safety assessment – advantages and limitations 
    Barbara Rothen-Rutishauser
    Adolphe Merkle Institute, University of Fribourg, Switzerland
  • 15:15 – 16:00 Discussion and Closing of the CE course

Session Abstract

This CEC will provide an extensive overview of the available in vitro airway models to study pulmonary toxicity, inflammation, immune effects and absorption. The pros and cons of the different models, and the purposes for which they can be used will be described. Areas where additional advances are needed will be identified and future perspectives will be discussed. 
The airways are an important site of entry for xenobiotics and respiratory exposure may lead to toxicity, inflammation or immune-mediated diseases, including asthma. Information on pulmonary toxicity/allergenicity of chemicals and particles is important in the risk assessment of chemicals, engineered nanomaterials, tobacco products and pharmaceuticals. One important adverse reaction in the lungs is inflammation and different in vitro models are available or in development to study this.
Traditional submerged airway models have limitations because the submerged aqueous environment influences the behavior and characteristics of substances and particles that are being studied, and thereby may affect their bioavailability and hazard assessment. In recent years, culturing and exposing lung models at the air-liquid interface (ALI) has been an important step forward. ALI enables more realistic culturing and exposure conditions of the cells compared to submerged exposure.
Currently available in vitro airway models range from simple monocultures of airway epithelium to complex three-dimensional cultures containing different cell types including epithelial cells, endothelial cells, fibroblasts, macrophages and dendritic cells. 3D ALI models may be fully differentiated and have a structure that retains or mimics some in vivo characteristics, such as functional cilia and the ability to secrete mucus. Ex vivo models such as human precision-cut-lung slices are used for research purposes as well. It is expected that in the coming years more progress in this area will be made, driven by the tissue engineering and efforts that are being made in the development of organotypic tissue models, including lung-on-a-chip.
Currently available in vitro airway models are used mainly for research purposes and are not yet ready for regulatory use. More experience with these models is necessary to get more confidence in the applicability for safety assessment of different xenobiotics. Also, better knowledge of mechanisms involved in toxicity, inflammation and immune-mediated diseases is important to develop mechanistically-relevant models and to identify predictive biomarkers for disease. Finally, insight into pulmonary absorption and distribution in vitro is essential to be able to perform risk assessment.

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