3 Minute 3Rs podcast: December 2022 transcript

 [NC3Rs] 

It’s the third Thursday of December, and you’re listening to 3 Minute 3Rs, your monthly recap of efforts to replace, reduce and refine the use of animals in research. To round off 2022 we are highlighting a paper for each R starting with a new method to help kidney organoids replace more in vivo studies.

Organoids have become valuable tools in human kidney research. However, the tissue cannot currently mature beyond a foetal stage due to a lack of vasculature in the organoid, which prevents oxygen and nutrients reaching the inner cells. One method to generate vascular structures in these organoids is to implant them in animals, but this means that the vasculature is derived from the animal, reducing the physiological relevance to humans and limiting the replacement potential of these organoid models.

In a recent paper in Scientific Reports researchers have developed a technique to generate vascular networks inside a kidney organoid. By co-culturing the organoids with perfused synthetic vessels already present in an organ-on-chip setup, endothelial cells were able to migrate from the existing channels to establish new vascular-like structures throughout the organoid. This proof-of-concept work improved organoid maturation and is an important step towards developing a fully human-derived vascularised 3D kidney model to replace the use of animals in a wide range of applications in kidney research, such as drug testing.

To learn more about this work, click the link in the description.

Next some considerations for how to improve experimental design by using masking potentially reducing the number of animals used in studies.

[NA3RsC]

Masking or purposely concealing which set of animals is the experimental versus control groups is an important technique to minimize bias and maximize experimental validity. A number of studies show that not masking can result in an overestimation of treatment efficacy and false positives. So why might researchers decide not to use masking techniques? 

Scientists at AstraZeneca, University of Brimingham, and the NC3Rs conducted a series of interview to reveal barriers and potential for improvement to masking. Key barriers were found to be related to practical constraints, resources, operations, prioritization of animal welfare, general knowledge, and work culture. Then, authors outline several specific and practical solutions to mask different types of experiments. 

To learn more, read the full paper in PLOS Biology. 

[NC3Rs]

And finally, a quantitative experiment severity assessment score to help refine the use of animals.

[Lab Animal]

In order to minimize suffering, it is critical to have objective methods for grading the severity of experiments and accurately estimate the levels of pain, suffering and distress experienced by animals. To date, most methods developed to assess severity involve subjective scorings.  

To overcome this limitation, Steven Talbot and colleagues developed a computational method that combines different parameters such as body weight, burrowing behavior, heart rate, temperature, and activity into a composite metric for grading procedure severity. This scoring system, named the RELSA score, could be used to grade severity in individual mice, subgroups, and to compare models such as sepsis, surgery, restraint stress and colitis.

This method, which provides a tool for quantitative severity assessment, could contribute to improving animal welfare, data quality, and reproducibility.

To learn more about this study, read the full paper in Frontiers in Veterinary Science.

[NC3Rs]

And that’s it for December’s episode. 3 Minute 3Rs is brought to you each month by Lab Animal, the North American 3Rs Collaborative, and the NC3Rs. Thanks for listening, and from everyone at the podcast, we hope you have a great festive period and start to the new year. Happy holidays and see you in 2023!