At present, animal-based models are the major test systems for assessing the tolerability and safety of chemical substances for regulatory purposes, and also for pivotal efficacy testing in pharmaceutical development. In spite of the high genetic similarity between many laboratory animals and humans, animal models are very poor predictors of human health effects and pathophysiological processes. Thus, models and testing strategies that are more relevant to human biology, are needed for these purposes. The best predictability is achieved with human organotypic models that mimic the microenvironment of human tissues. During their development, such models have to be characterised at the structural, genetic and functional levels, and compared to the respective human tissues. Their predictivity should be confirmed by using known reference chemicals with corresponding human data. The use of these methods in safety assessment and biomedical research, combined with the knowledge gained of the underlying biological processes on gene and protein expression, as well as on cellular signalling, will ultimately lead to better human science and animal welfare.
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A Normal and Biotransforming Model of the Human Bronchial Epithelium for the Toxicity Testing of Aerosols and Solubilised Substances
Zoë C. Prytherch and Kelly A. BéruBé
In this article, we provide an overview of the experimental workflow by the Lung and Particle Research Group at Cardiff University, that led to the development of the two in vitro lung models — the normal human bronchial epithelium (NHBE) model and the lung–liver model, Metabo-Lung™. This work was jointly awarded the 2013 Lush Science Prize. The NHBE model is a three-dimensional, in vitro, human tissue-based model of the normal human bronchial epithelium, and Metabo-Lung involves the co-culture of the NHBE model with primary human hepatocytes, thus permitting the biotransformation of inhaled toxicants in an in vivo-like manner. Both models can be used as alternative test systems that could replace the use of animals in research and development for safety and toxicity testing in a variety of industries (e.g. the pharmaceutical, environmental, cosmetics, and food industries). Metabo-Lung itself is a unique tool for the in vitro detection of toxins produced by reactive metabolites. This 21st century animal replacement model could yield representative in vitro predictions for in vivo toxicity. This advancement in in vitro toxicology relies on filter-well technology that will enable a wide-spectrum of researchers to create viable and economic alternatives for respiratory safety assessment and disease-focused research.
Magda Sachana, Alexandros Theodoridis, Cristina Cortinovis, Fabiola Pizzo, Evaggelos Kehagias, Marco Albonico and Francesca Caloni
The use of alternative methods for teaching purposes is gradually increasing in higher education. In order to evaluate the usefulness of non-animal based practical classes in veterinary science, and to inform on possible benefits and limitations of these teaching tools, a questionnaire was designed and distributed to students. Although there was no complete agreement among the student responses, it was apparent that the majority of the students would like traditional training methods to be paired with alternative approaches, and expressed their desire to be exposed to as many humane modes of learning as possible. In addition, the students agreed that alternative teaching methods for training in veterinary science can reinforce existing knowledge that is required at the clinical stage, and that they can be effective supplements to traditional training methods. It was also concluded from the study that the use of new alternative approaches is very much appreciated by the students, whereas the validity and effectiveness of these methods are debatable, suggesting that further optimisation, proper application and evaluation of these alternative methods is required.