While the standard of animal experimentation in the UK is generally very high, the aim of the Home Office appears to be to maintain the status quo, rather than to achieve significant Replacement and Reduction, and ensure Refinement
Trauma training is a crucial element of medical education in the civilian sector, as well as in the military sector. Its aim is to prepare physicians, medics and nurses for stressful and demanding emergency situations. Training methods include live-tissue training (LTT) on animal models and simulation-based trauma education. For LTT, blast, gunshot or stab wounds are inflicted on anaesthetised animals, mostly goats and pigs, but sometimes non-human primates. This training method raises ethical concerns, especially in the light of increasingly sophisticated simulation-based methods. Despite these non-animal alternatives, LTT is still widely used due to its presumed educational benefits. In this paper, the question of whether LTT can still be justified, is discussed. We developed a normative framework based on the premise that LTT can only be ethically justified when it yields indispensable benefits, and when these benefits outweigh those of alternative training methods. A close examination of the evidence base for the presumed advantages of LTT showed that it is not superior to simulation-based methods in terms of educational benefit. Since credible alternatives that do not cause harm to animals are available, we conclude that LTT on animal models is ethically unjustified.
In this study, we describe the isolation and immortalisation of primary murine alveolar epithelial cells (mAEpC), as well as their epithelial differentiation and barrier properties when grown on Transwell® inserts. Like human alveolar epithelial cells (hAEpC), mAEpC transdifferentiate in vitro from an alveolar type II (ATII) phenotype to an ATI-like phenotype and exhibit features of the air–blood barrier, such as the establishment of a thin monolayer with functional tight junctions (TJs). This is demonstrated by the expression of TJ proteins (ZO-1 and occludin) and the development of high transepithelial electrical resistance (TEER), peaking at 1800Ω•cm2. Transport across the air–blood barrier, for general toxicity assessments or preclinical drug development, is typically studied in mice. The aim of this work was the generation of novel immortalised murine lung cell lines, to help meet Three Rs requirements in experimental testing and research. To achieve this goal, we lentivirally transduced mAEpC of two different mouse strains with a library of 33 proliferation-promoting genes. With this immortalisation approach, we obtained two murine alveolar epithelial lentivirus-immortalised (mAELVi) cell lines. Both showed similar TJ protein localisation, but exhibited less prominent barrier properties (TEERmax ~250Ω•cm2) when compared to their primary counterparts. While mAEpC demonstrated their suitability for use in the assessment of paracellular transport rates, mAELVi cells could potentially replace mice for the prediction of acute inhalation toxicity during early ADMET studies.
The objective of this review is to report on whether, and if so, how, scientific research projects organised and managed within collaborative consortia across academia and industry are contributing to the Three Rs (i.e. reduction, replacement and refinement of the use of animals in research). A number of major technological developments have recently opened up possibilities for more direct, human-based approaches leading to a reassessment of the role and use of experimental animals in pharmacological research and biomedicine. This report reviews how projects funded by one of the research funding streams, the Innovative Medicines Initiative (IMI), are contributing to a better understanding of the challenges faced in using animal models. It also looks how the results from these various projects are impacting on the continued use of laboratory animals in research and development. From the progress identified, it is apparent that the approach of private–public partnership has demonstrated the value of multicentre studies, and how the spirit of collaboration and sharing of information can help address human health challenges. In so doing, this approach can reduce the dependence on animal use in areas where it has normally been viewed as necessary. The use of a collaborative platform enables the Three Rs to be addressed on multiple different levels, such that the selection of models to be tested, the protocols to be followed, and the interpretation of results generated, can all be optimised. This will, in turn, lead to an overall reduction in the use of laboratory animals.
Progress toward the acceptance and application of validated alternative test methods as replacements for animal tests, is being frustrated by the unsatisfactory procedures involved in approving new test guidelines and deleting existing ones