3 Minute 3Rs November 2019

The November episode of 3 Minute 3rs, brought to you by the NC3Rs (www.nc3rs.org.uk), the North American 3Rs Collaborative (www.na3rsc.org), and Lab Animal (www.nature.com/laban).Papers:1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662399/2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5371849/3. https://pubs.rsc.org/en/content/articlelanding/2019/LC/C9LC00160C [NA3RsC] Evaluation of developmental and reproductive toxicity is a key aspect of drug development. Each year, 5-7% of newborns worldwide are born with serious birth defects, a number correlated to increased use of pharmaceutical drugs for managing health conditions. Reproductive toxicology studies account for roughly 90% of all animal use in toxicological safety assessment. The FDA requires that these animal studies be performed in two species, often rodents and rabbits. The embryonic stem cell test (EST) is an alternative in vitro assay that does not require the use of pregnant animals but is not yet powerful enough to provide a complete alternative, as it only considers the direct toxicity of compounds. Consequently, in vivo animal models are still required to evaluate effects on drug metabolism.This research established an in vitro platform (metaEST) which uses 3D embryoid bodies and 3D primary human liver microtissues on a chip to evaluate alterations in metabolism. Not only does this significantly reduce the number of animals required, these results demonstrate the platform’s ability to evaluate metabolic effects that are missed using the standard EST assay and mimic physiologically relevant conditions in vitro.[NC3Rs] Botulinum neurotoxin can cause fatal paralysis following ingestion or infection of a wound and is a potential bioterrorism agent. Therefore, the ability to quickly and accurately detect the toxin in a sample is crucial. The current method used to detect the toxin is the mouse lethality bioassay, where mice are injected with neurotoxin to determine the LD50 value, or the dose that kills half the animals. This uses approximately 70,000 mice per year in the UK and more than 600,000 mice annually worldwide and causes severe suffering prior to death. Researchers at the Centers for Disease Control and Prevention in the US have developed a mass spectrometry-based method that can successfully identify botulinum neurotoxin activity for the four human-toxic serotypes. It is faster - the test can be done in just 4- 6 hours on the spectrometer rather than the 1- 4 days typically required by the mouse bioassay. The test also requires samples with volumes as low as 100 µL per toxin type, instead of the 1 mL required for the mouse bioassay, avoiding the problem of insufficient sample volumes. This mass spectrometry- based assay is a fast and accurate alternative to the mouse bioassay and further implementation of the technique has the potential to reduce the number of animals used for this purpose. [LA] Tissues do not exist in isolation from one another. As increasingly sophisticated organ-on-chip technologies continue to emerge, many researchers want to link those chips together to mimic multi-organ systems. That’s been easier said than done. Yi-Chin however has been working on making better connections. The new microfluidic platform she helped developed consists of modular tissue and fluid control units, referred to as TILE modules. With the help of magnetic connectors, these modules can be arranged and re-arranged into different perfusion circuits as needed. It’s backwards compatible too, meaning existing microfluidic devices can be used. The team involved demonstrated the platform in action with 2 and 3 tissue modules that mimic liver-mediated bio activation in response to a nutraceutical and a cancer prodrug. All using human cells, rather than animal models. Hosted on Acast. See acast.com/privacy for more information.