An In Vitro Human Tissue Equivalent Model of Respiratory Epithelia for Toxicological Screening of Inhaled Nanoparticles

AUTHORS: Kelly BéruBé, Tracey Hughes, Zoë Prytherch, Keith Sexton, Lata Koshy, Tim Jones

ADDRESS: School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3US, Wales, UK  

BIOGRAPHY: Dr Kelly BéruBé is a Lecturer in Cell Biology and Director of Nanoscience Initiatives at the School of Biosciences. Her research focuses on determination of intelligent biomarkers of exposure and harm in respiratory epithelia, with a particular interest in understanding how environmental pollutants compromise lung biochemistry and alter gene and protein expression profiles. Her work on in vitro alternatives for in vivo inhalation toxicology was awarded with the UK NC3Rs ‘Replacement’ Prize in 2007 (Wellcome Trust) and the ‘Science & Technology Innovation’ Prize 2007 (Cardiff University).  

ABSTRACT: Ethically-driven initiatives and the 2013 EU Cosmetic Directive banning repeat exposure tests in animals are making the need to develop alternative inhalation toxicology testing increasingly pressing. The work undertaken focused on toxicity testing of engineered nanoparticles used in aerosolized consumer products (e.g., pharmaceutical drugs, hair-sprays) and environmental NP (e.g. diesel exhaust particles, metal aerosols), with the aim of identifying key molecular biomarkers for the onset of damage in the lung. Normal human bronchial epithelial cells were tissue-engineered from medical waste (heart/lung transplant donors) to develop 3-dimensional cell cultures. Cultured cells formed tissue closely resembling epithelia of the human respiratory tract, with distinct cell types functioning as in vivo. NP can now be tested as though they have been inhaled and, given the endpoint data comes from human-derived, primary tissue instead of animal, there is no need to extrapolate results. Data is more representative of human lung responses/mechanisms and used with greater confidence in its accuracy. The model offers higher/quicker output in comparison to animal testing and provides a viable, low cost alternative to traditional toxicity testing methods.


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