November 2020

You’re listening to the November episode of 3 Minute 3Rs.

The papers behind the pod:

1.       Three-Dimensional Human Alveolar Stem Cell Culture Models Reveal Infection Response to SARS-CoV-2. Cell Stem Cell

2.      Improving reproducibility in animal research by splitting the study population into several ‘mini-experiments’. Sci Rep

3.      Three Pillars of Automated Home-Cage Phenotyping of Mice: Novel Findings, Refinement, and Reproducibility Based on Literature and Experience. Front Behav Neurosci


It’s the 3rd Thursday of November and you’re listening to 3 Minute 3Rs, your monthly recap of efforts to replace, reduce, and refine the use of animals in research. This month, we’ve got one paper for each R – let’s jump right in with a replacement.


Severe acute respiratory coronavirus 2 (SARS-CoV-2), the cause of the current pandemic, infects human lung alveolar type 2 (hAT2) cells. To develop strategies for efficient prevention, diagnosis and treatment, we need to understand the disease pathogenesis. Using human cells in a physiologically relevant system has advantages over using cells lines and animal models including allowing viral replication. Organoid systems, using cells from the kidney, liver and airway, have been used in SARS-CoV-2 research however there have been technical challenges in using hAT2 cells in this way.

Scientists in Korea in collaboration with research groups in the UK have successfully developed a 3D culture technique for primary human hAT2 cells that has been used to investigate the infection response to SARS-CoV-2. This 3D culture has provided an enhanced understanding of how SARS-CoV-2 causes such severe disease, whilst reducing reliance on animal models. The culture can also be combined with other techniques, such as co-culture experiments with immune cells and high throughput in vitro screening of antiviral agents, crucial to select successful treatments. Finally, it can be used for research for other respiratory diseases, reducing the reliance on animal models in respiratory research further.

Want to know more? Check out the paper in the journal Cell Stem Cell.

On to the next R: reduction

[LA] No matter how carefully you try to control every little detail in your experiments, variables in your lab are going to differ from those elsewhere. As a result, a positive result in your hands may fail to replicate in the hands of another – with wasted animals in between. Rather than trying to standardize things further, a growing body of literature suggests a little more heterogeneity may be in order to improve reproducibility and reduce overall animal use.  

Multi-lab study designs are promising, but these can be logistically challenging. For the single lab that wants to introduce heterogeneity into their studies, researchers at the University of Munster suggest a simple solution: split that experiment up into several miniature versions.

Rather than testing every animal all at once, the proposed mini-experiment design spreads those animals out across several time points. The idea being, things will change a bit in the lab in between testing rounds, similar to what might be expected if animals were instead being tested in separate facilities.

In comparisons of four mouse strains across four replicate behavioral &...

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