You’re listening to the June 2021 episode of 3 Minute 3Rs 

The papers behind the pod: 

Winning paper: 

Pellegrini L et al. (2020). Human CNS barrier-forming organoids with cerebrospinal fluid production. Science 369(6500): eaaz5626. doi.org/10.1126/science.aaz5626.  

Highly commended: 

Ashworth J et al. (2020). Peptide gels of fully-defined composition and mechanics for probing cell-cell and cell-matrix interactions in vitro. Matrix Biology 85-86: 15-33. doi.org/10.1016/j.matbio.2019.06.009. 

[Transcript]

It’s the 3rd Thursday of June, 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 a special double feature to highlight the results of the 2020 3Rs Prize, awarded by the NC3Rs and sponsored by GSK. Let’s start with the winner: Laura Pellegrini at the MRC Laboratory of Molecular Biology, for her animal-replacing organoid work.  

NA3RsC 

Deep within each of our brains, there’s a vital fluid providing essential nutrients and signaling molecules while protecting the brain from toxic compounds. It’s called the cerebrospinal fluid which is produced by the choroid plexus.  

Our understanding of this fluid and organ is limited due to the difficulty in studying them. In turn, many new drugs developed for the central nervous system have failed because of lack of efficacy, inability to cross the blood-brain barrier, or limited translation from animals. 

But now, Dr. Pellegrini and her colleagues have developed a human choroid plexus organoid. This organoid has a selective barrier that quantitatively predicts the permeability of small molecules into the brain. It even secretes a liquid very much like cerebrospinal fluid.  

Overall, this model holds great promise for deeper study into this incredible part of our bodies. To learn more, read the full paper in Science. 

2020 also brought us highly commended replacement to mouse-derived Matrigel.  

NC3Rs  

A cell’s environment has a lot of influence on their behavior so for cells to be the best experimental representative their environment needs to be as similar to in vivo as possible. In many research areas, there is now a move towards 3D culture techniques using biomaterials as a matrix, providing both structure and cell-matrix interactions. Often these matrices are animal-derived, such as Matrigel which is derived from mouse sarcomas. Approximately one hundred mice can be required to produce the Matrigel needed by a single research institute every year. However, the chemical components of Matrigel are not well defined affecting the reproducibility of studies and given the number of different cell types, organs and tissues, a one-size-fits all approach is unlikely to be the best representation of an in vivo situation. 

Dr Jennifer Ashworth was highly commended in the 2020 3Rs Prize for her work published in Matrix Biology detailing a non-animal derived synthetic hydrogel that can replace the use of Matrigel. The hydrogels are derived from a commercially available precursor peptide. This ‘blank slate’ can then be ‘tuned’ altering a hydrogel’s stiffness and composition by adding proteins and sugars to replicate different in vivo environments. Check out Jenny’s paper to learn more. 

And with...

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