3 Minute 3Rs

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

The papers behind the pod:

1.      PCR Testing of Media Placed in Soiled Bedding as a Method for Mouse Colony Health Surveillance. JAALAS  https://doi.org/10.30802/AALAS-JAALAS-20-000096

2.      New mosquito repellency bioassay for evaluation of repellents and pyrethroids using an attractive blood-feeding device. Parasites & Vectors https://doi.org/10.1186/s13071-021-04656-y

3.      Lung cancer organoids analysed on microwell arrays predict drug responses within a week. Nature Communications https://doi.org/10.1038/s41467-021-22676-1

 Transcript:

It’s the 3rd Thursday of May 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’re looking at animal free options for testing mosquito repellents and cancer therapies. But first, can we replace sentinel animals for health monitoring?

[NA3RsC]

To support high-quality research data, it’s important to ensure that colony animals are healthy. Traditionally, rodent health surveillance is done through dirty bedding sentinel animals that act as a sort of canary in the coal mine. But what if, we could replace these animals, reduce husbandry time, and get even better data? New research shows that we can, regardless of the type of caging we use.

Researchers from Emory University developed an effective protocol to conduct environmental monitoring in both individually ventilated racks filtered at the cage level and static cages. The most effective method was to simply replace dirty bedding sentinel rodents with 10 flocked swabs and cage shaking. This method was actually MORE effective than traditional sentinel animals. To learn how to replace your sentinel rodents with environmental monitoring, read the full paper online.

On to repelling mosquitoes

[NC3RS]

The threat of mosquito-borne infectious diseases is rising, fueled in part by climate change and increases in international travel. Consequently, there is a growing interest in developing textiles treated with mosquito repellents and a growing need to test potential products.

These test methods must be standardized, but this process requires a regular supply of animal blood for the mosquitos to feed on. Using living animals for this purpose raises animal welfare concerns. To address these issues, Morimoto and colleagues have developed a new attractive blood-feeding device consisting of a feeding unit with a reservoir of equine blood overlaid with a plastic membrane. The mosquitos can artificially feed on equine blood by penetrating the membrane, avoiding the use of live animals. The authors describe using the device to evaluate how mosquitos responded to three chemical repellents, producing highly accurate and reproducible results. The attractive blood-feeding device could also be used to develop new repellent chemicals and learn more about mosquito physiology.

Got an itch to learn more about this refined test system – follow the link in the description.

[LA] And finally, we’ve all heard of patient-derived xenograft mouse models. To many in the cancer field, these patient-personalized mice have been important tools for testing patient responses to treatments. PDX models are however expensive, and they take a long time and a lot of mice to produce. Mice, however, aren’t the only option for personalized medicine. As in vitro technology advance, patient derived organoids are emerging alternatives.

In a new paper published in the journal Nature...

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

The papers behind the pod:

1.       Identification of individual zebrafish (Danio rerio): a refined protocol for VIE tagging whist considering animal welfare and the principles of the 3RS. Animals  11, 616 (2021) https://doi.org/10.3390/ani11030616

2.      Enrichment for laboratory zebrafish – a review of the evidence and challenges. Animals 11, 698 (2021) https://doi.org/10.3390/ani11030698

3.      Research relevant background lesions and conditions: ferrets, dogs, swine, sheep, and goats. ILAR J ilab005 (2021) https://doi.org/10.1093/ilar/ilab005

4.      *Bonus* Research-relevant background lesions and conditions in common avian and aquatic species. ILAR J ilab008 (2021) https://doi.org/10.1093/ilar/ilab008

Transcript:

It’s the 3rd Thursday of April 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 some zebrafish refinements, plus a refresher on some basics for a bunch of different animals. But first, ID please.

[NC3Rs]

If you’ve got a tank full of fish that look identical, how do you make sure you can tell them apart? The zebrafish research community have tried various tagging methods, but until now there hasn’t been a refined and standardized method that can be used on a large scale.

In a new paper in Animals, Anita Rácz and colleagues describe such a method for tagging zebrafish using visible implant elastomer, or VIE. This method is widely used for marking large fish and other aquatic organisms and involves injecting a small amount of coloured elastomer under the fish’s skin.

As well as explaining their refined protocol, including appropriate anaesthesia and analgesia, Rácz and colleagues compare it to a previous protocol and show that it offers significant welfare improvements, including a ten-fold reduction in mortality following the tagging procedure. With zebrafish being used in thousands of labs around the world, particularly in genetic research, this work is bound to make a big splash.

While we’re thinking about zebrafish, have you thought about their tanks look like lately?

 [NA3RsC]

Zebrafish have rapidly become one of the most common research animal species with over 5 million fish used worldwide. Currently, most of these fish are housed in barren tanks with no environmental enrichment.

But in a recent review in Animals, the RSPCA Science Department describes current evidence supporting zebrafish enrichment. Its provision improves zebrafish welfare, behavior, and physiology, which can lead to better science. 

One well-supported and fairly easily implemented enrichment is using an image of gravel on the bottom of tanks. The paper also discuss evidence for social housing, plastic plants, live food, and more. To learn more about the current evidence for zebrafish enrichment, read the full paper online.

[LA] And finally, a double feature. A lot of different animals turn up in research labs beyond rodents. But regardless of what species you are using, you need to know what’s normal and what’s not for a given animal in order to accurately interpret any experimental results.  How well do you know an animals’ anatomy and how it differs from the humans they are intended to model? Is that lesion intentional, or a spontaneous...

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

The papers behind the pod:

1.      Novel three-dimensional biochip pulmonary sarcoidosis model. PLoS One https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245805

2.      A new group housing approach for non-human primate metabolism studies. Journal of Pharmacological and Toxicological Methods https://doi.org/10.1016/j.vascn.2020.106947

3.      The contribution of environmental enrichment to phenotypic variation in mice and rats. eNeuro https://doi.org/10.1523/ENEURO.0539-20.2021

Transcript:

It’s the 3rd Thursday of March 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 two refinements to cover – a paper for primates and one for rodents too. But first, let’s have some lung chips.

[NC3Rs]

Despite being first described towards the end of the 19th century, a lot about sarcoidosis remains unknown. The granulomas characteristic of the disease can affect almost any organ in the body, but the lung is most commonly affected, and associated with the highest morbidity and mortality in patients.

Pulmonary granulomas can be modelled in animals, but as there is no known specific genetic component, transgenic animals representing the human condition cannot be easily created. Instead, animals are typically pre-sensitised to environmental agents, such as bacteria, and then repeatedly exposed to the same antigens to form granulomas.

Using organ-on-a-chip technology, Calcagno et al introduced granulomas, isolated from patient blood samples, to its air-lung interface. They were able to detect macrophages and lymphocytes from the developed granulomas in the interface and inflammatory cytokines being released into the culture media. As well as better understanding the mechanisms behind sarcoidosis, the system can also be used to develop new treatments, with high-throughput potential and AI compatibility. You can read more about the method by following the link in the description.

Next up, thinking beyond single housing

[NA3RsC] Before new drugs are approved by regulatory bodies, they must undergo testing to understand their absorption, distribution, metabolism, and excretion. This is a key step in assuring their safety and efficacy. Sometimes, when there is no scientific alternative, non-human primates are used for these tests.

Traditionally, for metabolism studies animals are singly-housed in cages that limit normal vertical movement & social behaviors which negatively impacts welfare. However, recently, Novo Nordisk, Covance, & other collaborators worked together to design a refined group housing metabolism cage. This cage has extensive advantages such as more space, better socialization, and less stress. Importantly, excretion data from this cage is comparable to the singly housed cages which supports its suitability for future metabolism studies.

To read more, see the full paper online.

And finally, a reminder that enrichment is a good thing.

[LA] Researchers often to want to control as many variables as they can in their experiments. However, providing environmental enrichment is beneficial for the welfare of...

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

The papers behind the pod:

1.      In Vitro Tests for Assessing the Neutralizing Ability of Snake Antivenoms: Toward the 3Rs Principles. Frontiers in Immunology https://doi.org/10.3389/fimmu.2020.617429

2.      The Impact of Acute Loud Noise on the Behavior of Laboratory Birds. Frontiers in Veterinary Science https://doi.org/10.3389/fvets.2020.607632

3.      A multicomponent screen for feeding behavior and nutritional status in Drosophila to interrogate mammalian appetite-related genes. Molecular Metabolism https://doi.org/10.1016/j.molmet.2020.101127

Transcript:

It’s the 3rd Thursday of February 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 work on finches and flies to feature, but first, let’s review what we know about applying the 3Rs to antivenom research.

[NA3RsC] Every year, venomous snakebites kill over 100,000 people and maim over 400,000 more. Treatment for these bites comes in the form of antivenom, which is typically made from the plasma of horses immunized with snake venom. Before being used in humans, this plasma is tested in mice to ensure that it’s safe and effective. But unfortunately, these tests require large number of mice and can cause significant pain & distress.

A new paper in Frontiers in Immunology calls for an urgent need to strengthen the implementation of the 3Rs in antivenom research. This is a challenging task due to the complexity of snake venom, but there has been progress. For replacement & reduction, the authors recommend correlated in vitro surrogate assays. For refinement, they recommend routine analgesia, improved housing, and re-designed protocols. 

To learn more about how the 3Rs can be implemented in antivenom research, read the full paper online.

[LA] Next up, we all know that noise can be a cause for concern for laboratory rodents, but what about for the other species we keep in the lab? Mitigation measures for mice and rats – for example, those low frequency, quote unquote silent fire alarms – might not be so silent for other animals. A study published in Frontiers in Veterinary Science considers whether weekly fire alarm tests might be stressing out a colony of zebra finches.

Pairs of finches were recorded before and after they were exposed to the fire alarm and again during alarm-free control sessions.

Even though the alarm only lasted a few seconds and the zebra finches had been born and raised with the noise, they still took note. Movement decreased, and the usually chatty birds fell a bit silent for at least fifteen minutes following the disruption. Instead, they sat perched in the middle of their cages and increased preening of one another, a possible fear response. The results suggest more work needs to be done to assess the welfare of birds in response to noise disturbances.

And finally, can flies replace mice for obesity research?

[NC3Rs] Obesity is a serious public health issue due to its link with other co-morbidities such as type 2 diabetes and cardiovascular disease. Someone’s response to the modern “obesogenic” lifestyle is largely due to their genetics and murine models can be used to explore these effects. But studying genes of interest requires extensive breeding programmes and significant resources to generate and phenotype...

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

The papers behind the pod:

1.      Internal consistency and compatibility of the 3Rs and 3Vs principles for project evaluation of animal research. Laboratory Animals https://doi.org/10.1177/0023677220968583

2.      Noise and Vibration in the Vivarium: Recommendations for Developing a Measurement Plan. JAALAS https://doi.org/10.30802/AALAS-JAALAS-19-000131

3.      A human tissue screen identifies a regulator of ER secretion as a brain-size determinant. Science  https://doi.org/10.1126/science.abb5390

Transcript:

It’s the 3rd Thursday of January and you’re listening to the first 3 Minute 3R of the new year. Each month, we recap three efforts to replace, reduce, and refine the use of animals in research. To kick off 2021, we’ll be discussing the issue of noise in the vivarium, and consider an organoid rather than animal-based approach for studying brain development. But first let’s hear about another letter-based trio: the Three Vs. 

[NC3Rs] Anyone involved in animal research must consider how to both minimise harm to animals and maximise scientific progress. The 3Rs are one framework for doing this, but they are not the only one. There’s also harm-benefit analysis, as well as the 3Vs of scientific validity – though modern definitions of the 3Rs, specifically reduction, do incorporate validity as a way to avoid unnecessary animal use. A review by Matthias Eggel and Hanno Würbel in Laboratory Animals explores further how these three ideas can work together.

They explain that while there is little internal conflict between the 3Vs, there is potential for some in the 3Rs. Specifically, between refinement and reduction, where judgements may have to be made based on “more animals experiencing less harm” versus “fewer animals experiencing more harm”. Ethical review based on harm-benefit analysis can help solve such questions. Eggel and Würbel also look at the compatibility between the 3Vs and the 3Rs, finding that any potential conflicts can be resolved either by harm-benefit analysis or by good experimental design – for example, using randomised block designs to minimise sample size while maximising reproducibility. Ultimately the authors show that these three concepts can be integrated, forming a logical structure for better animal welfare and better science.

Next, let’s make some noise – or actually, don’t.

[NA3RsC] Did you know that mice and rats can hear sounds that humans can’t? We can only hear up to 20 kHz, but mice and rats can up to 90 kHz. Furthermore, as they are nocturnal animals with relatively poor vision, noise and vibration are heavily used by rodents to navigate their environment. Unfortunately, these factors are rarely measured, can vary greatly from facility to facility or even room to room, and have the potential to cause both animal distress and be a confounding variable in scientific studies.

A new paper in the Journal of the American Association for Laboratory Animal Science outlines these concerns and presents recommendations for developing a measurement plan. For example, facilities should develop a written plan, assess noise & vibration annually and as needed, and, importantly, maintain chronic noise below the threshold of negative animal welfare or scientific impacts. To learn more, read the full paper online.

 And finally, we’ll finish with a replacement paper.

[Lab...

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

The papers behind the pod:

1.      Protective cranial implant caps for macaques. Journal of Neuroscience Methods https://doi.org/10.1016/j.jneumeth.2020.108992

2.      The ‘Cage Climber’ – A new enrichment for use in large-dimensioned mouse facilities. Applied Animal Behaviour Science https://doi.org/10.1016/j.applanim.2020.105078

3.      Skin swabbing is a refined technique to collect DNA from model fish species. Scientific Reports https://www.nature.com/articles/s41598-020-75304-1

Transcript:

It’s the 3rd 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. For the last episode of 2020, we’re focusing on refinements for three different animals. Let’s start big.

[NC3Rs]

Measuring the electrical activity of neurons during sensory or motor activities can reveal how the brain works.

Macaques are often used in these studies as their brains most closely resemble those of humans. Devices to access the brain and to fix the head for stable electrophysical recordings are surgically implanted under general anaesthesia. These implants are designed to integrate with the skull however the surgical wound can be slow to heal. The animals are also prone to picking at the sutures increasing the likelihood of infection.

A new paper published in Journal of Neuroscience Methods from technical and research staff at the University of Oxford and Newcastle University details how a protective cap can be used to promote wound healing. The plastic cap is adjustable to cover most primate cranial implants and can be affixed whilst the animal is under anaesthetic. Across the two facilities, the protective head cap reduced wound opening, the need to re-suture and the length of time animals needed to be administered analgesia and antibiotics.

You can find out more about the cranial caps by following the link in the description.

Next, a refinement for mice:

[NA3RsC]

Proper enrichment of mice in their home cages is important to decrease mouse stress, reduce stereotypic behaviors, and improve well-being. When developing new enrichments it’s important to ensure they benefit both males & females and do not have unintended experimental effects or increase data variability.

A new paper in Applied Animal Behavior Science describes the development and testing of a new enrichment made from recycled cage lids. Results showed that naive mice were extremely interested in these enrichments. Furthermore in a test battery assessing locomotion, anxiety, sociability, and stress physiology there was no impact on data results or variability. Furthermore, the enrichments reduced aggression.

Ultimately the authors recommend the use of structural enrichments and nesting material to satisfy mouse physical and thermal needs. To find out more, read the full paper online.

[Lab Animal]

And finally, let’s not forget about our fish. When a zebrafish or stickleback needs to be genotyped, that’s usually accomplished via fin clipping. But, a growing body of literature suggests that fish might not be too fond of being removed from their tanks and waking up some time later with a small bit of their caudal fin missing. The tissue grows back, but studies have shown increases in cortisol and anxiety-like behavior in fin clipped fish, which may affect their welfare and the scientific results obtained with them.

A new study led by William Norton at...

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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  https://doi.org/10.1016/j.stem.2020.10.004

2.      Improving reproducibility in animal research by splitting the study population into several ‘mini-experiments’. Sci Rep  https://doi.org/10.1038/s41598-020-73503-4

3.      Three Pillars of Automated Home-Cage Phenotyping of Mice: Novel Findings, Refinement, and Reproducibility Based on Literature and Experience. Front Behav Neurosci https://doi.org/10.3389/fnbeh.2020.575434

Transcript:

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.

[NC3Rs]

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

The papers behind the pod:

1.       The epidemiology of fighting in group-housed laboratory mice. Scientific Reports https://www.nature.com/articles/s41598-020-73620-0

2.      Development of a miniaturized 96-Transwell air–liquid interface human small airway epithelial model. Scientific Reports https://www.nature.com/articles/s41598-020-69948-2

3.      Publication rate in preclinical research: a plea for preregistration. BMJ Open Science https://openscience.bmj.com/content/4/1/e100051

Transcript:

It’s the 3rd Thursday of October 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’ll take a look at preclinical publications and a microplate system to study small airway epithelium. But first, can we stop the fighting?

[NA3Rs] Mice, the most commonly used mammal in scientific research, can sometimes be quite aggressive to each other in their home cages which can lead to serious injuries. In fact, mouse aggression is arguably the most common preventable morbidity factor. But its risk factors are little understood.

However, a new epidemiological publication looked at mouse aggression in 60,000 cages across 1 year. They found that the biggest risk factor was housing. On average, 15% more fights were seen in individually ventilated cages with corn cob bedding than compared to static cages with wood chip bedding. Furthermore, they found that industry-standard cage-side checks for mouse aggression missed the majority of fights. They also found that fighting peaked during the summer months, on the top rack, and when racks were parallel versus perpendicular.

To learn more about their findings, read the full paper in Scientific Reports

Next, an animal free epithelium model.

[NC3Rs] The pharmaceutical industry is increasingly turning to human cell-based in vitro methods as a screening tool to identify promising drug candidates during the drug development process. Not only do these models reduce reliance on animals, they can also reduce drug attrition and provide a more cost-effective approach while allowing for higher throughput. Research into drugs for respiratory diseases is no exception to this trend, but small airway epithelial cells are particularly tricky to obtain from clinical sampling and struggle to divide ex vivo.

Overcoming these issues means maximising the information you can get out of a limited number of cells. In a new paper, Teresa Bluhmki and colleagues at Boehringer Ingelheim describe a new miniaturised method of culturing small airway epithelial cells within a 96-well plate. After four weeks, an epithelium was produced with a similar composition to those created in 24-wells, which was then validated for use in drug discovery. Another exciting feature of the method is that it can be automated, allowing for even more efficient research into treatments for Idiopathic Pulmonary Fibrosis and other respiratory diseases.

Interested in learning more about this small but mighty technique? Check out the paper in Scientific Reports.

[Lab Animal] And finally, let’s shine some light on preclinical publication. It’s no secret that a lot of different animals are used in biomedical research each year. But how many of those animals end up in a publication describing the scientific results obtained with them?  If University Medical Center Utrecth is any example, not many. 

A look at a selection of animal study protocols approved...

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

The papers behind the pod:

1.       Multicellular 3D Neurovascular Unit Model for Assessing Hypoxia and Neuroinflammation Induced Blood-Brain Barrier Dysfunction. Scientific Reports https://www.nature.com/articles/s41598-020-66487-8

2.      Automated and rapid self-report of nociception in transgenic mice. Scientific Reports https://www.nature.com/articles/s41598-020-70028-8

3.      Zebrafish as an alternative animal model in human and animal vaccination research Laboratory Animal Research https://labanimres.biomedcentral.com/articles/10.1186/s42826-020-00042-4

Transcript:

It’s the 3rd Thursday of September, 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’ll let mice do the talking and hear about using zebrafish to study vaccines. But let’s start with an update on an organoid.

[NC3Rs] Back in 2018, Goodwell Nzou and colleagues from the Wake Forest Institute for Regenerative Medicine in the United States published their microscopic replica of the human brain, formed from the six major neural cell types including neurons and immune cells. This miniature organ, or organoid, not only promoted the formation of a blood brain barrier, the resultant barrier was also functional.

Fast forward to today, and in a publication in Scientific Reports, Nzou et al have demonstrated how this platform could be used in drug screening. Disruption of the blood brain barrier in neurological disorders, such as ischaemic stroke, is common, exacerbating the injury to the brain and contributing to cognitive impairment. By culturing the organoid in hypoxic conditions, replicating low oxygen resultant from a stroke, they were able to show expression of proteins critical for blood brain barrier function were altered, leaving the barrier disrupted and leaky. 

Inducing ischaemic stroke in rodents is associated with significant welfare concerns, including death, weight loss, sensorimotor defects and seizures. Using organoids can replace some of these experiments in disease modelling and therapeutic development, so this new publication could have big implications for the 3Rs. You can find out more by following the link in the description.

[Lab Animal] Next, some self-reporting of pain.  Mice are inevitably used to study the mechanisms underlying nociception, with the goal of better understanding pain in people and how to treat it. Many studies rely on reflex assays, but interpreting these can be subjective and there’s uncertainty about what the mice are feeling and reacting to. This can limit study of the neuronal pathways involved and the affective components of pain perception.

A new study in the journal Scientific Reports presents an assay in which transgenic mice learn to self-report exposure to a nociceptive stimulus. The mice, head fixed in the current study, were trained to lick a water spout in response to optogenetic stimulation of heat-sensing neurons in their hind paw. The authors suggest that self-reporting may provide a quicker read-out of nociception that may better reflect the animals’ affective state, and hopefully help make results with the mice more translationally relevant.

And we’ll finish with a topic that’s likely on many of our minds: vaccines.

[NA3RsC] You are probably aware of the recent push to develop a vaccine for COVID-19. Before these vaccines are given to people...

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