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Innovation examples
HealthToxicology
Zebrafish in toxicity testing
Zebrafish are increasingly recognised as a useful model for toxicity testing of chemical substances. Testing strategies are becoming more based on mechanisms of toxicity structured in adverse outcome pathways describing the chain of events leading to toxicity or disease. Using a battery of dedicated in vitro and in silico assays, insight can be gained in how exposure leads to disease. For certain diseases it is known that toxicity relies on the interaction between different organs and cell types, which requires research on whole organisms in addition to simple in vitro models. The zebrafish is considered a valuable whole organism model in a mechanism-based testing strategy. At RIVM, the zebrafish embryo model is used for testing the effect of chemical substances on several adverse outcomes and diseases.
For more information see: https://ehp.niehs.nih.gov/doi/10.1289/EHP9888; https://doi.org/10.3390/ijerph18136717; www.linkedin.com/in/harm-heusinkveld
Expert interviews
HealthEducation
Daniela Salvatori, TPI Utrecht: We aim for better science with less animals
Prof. dr. Daniela Salvatori, chair of TPI Utrecht, presents the aims of the local TPI group and invites all who want to share their ideas or questions on the transition towards animal-free innovations to get in touch via uu.nl/tpi.
Innovation examples
EducationInnovation
Avatar Zoo - teaching animal anatomy using virtual reality
Animals are essential to train the next generation of scientists understand diseases and develop treatments for humans as well as animals. Therefore, animals are used for educational purposes. Technologies such as Virtual Reality and Augmented Reality can be employed to reduce the number of animals in the future. Prof. Dr. Daniela Salvatori is working on the development of 'Avatar Zoo' together with UMCU and IT. Live animals are replaced by holographic 3D in this flexible platform. With these holograms one is able to study the anatomical, physiological and pathological systems and processes of all kinds of animals.
Avatar Zoo won the Venture Challenge 2021 for the development of virtual reality models that can be used for anatomy classes and practical training.
Projects and initiatives
HealthIn vitroOrgan-on-Chip
SCREENED: developing 3D thyroid models
The European collaborative project SCREENED aims to develop three-dimensional (3D) cell-based in vitro tests to better characterize the effects of endocrine disruptors (EDs) on thyroid gland function. This method will overcome the limitations of existing tests, being more sensitive at low doses of exposure to chemicals, and enabling the prediction of their toxicity on human health in a sex-specific manner. The ambition of the SCREENED project is that these new 3D in vitro tests, as well as the increased knowledge about adverse reactions after exposure to EDs, will be used for regulatory purposes, ultimately to improve human health.
Innovation examples
HealthIn vitroOrgan-on-Chip
An iPSC-derived blood-brain barrier to model neurodegeneration
The blood-brain barrier is a layer of cells that protects our brain from harmful compounds. However, due to this tight barrier, many drugs to treat neurological diseases cannot enter the brain either.
There are currently no good models to test these types of drugs. Henrique Nogueira Pinto is a PhD candidate at the Vrije Universiteit in Amsterdam. He is developing a blood-brain barrier model coupled to mini-brains. With this model, he aims to more reliably test how drugs can be transported over the blood-brain barrier and what their effect on the brain is.
Click on the info button for the full version of the video. Click here (https://fluidsbarrierscns.biomedcentral.com/articles/10.1186/s12987-022-00316-0#Sec3) for a review of the current status of in vitro models for the blood-brain barrier.
TPI.tv videos
InnovationPolicyBeginner
TPI.tv: improving science through animal-free innovations and research
Introducing TPI.tv : a video platform by experts striving to improve science through animal-free innovations and research.
Meetings & conferences
HealthIn vitroAdvanced
Liquid marbles for cardiac organoids development
Advances in three-dimensional (3D) culture techniques have shown several advantages over 2D cultures, especially by more accurately mimicking the in vivo environment. This has led to improved reproducibility and reliability of experimental results, which are important criteria in disease modelling and toxicity testing. Induced pluripotent stem cells (iPSC) provide an unlimited source for the derivation of all cell types of the adult body, including cardiomyocytes. To improve the current culture methods for multicellular cardiac spheroids, such as the hanging drop method, we explored the use of hydrophobic powders. Fumed silica nanoparticles can be used to encapsulate liquid drops, which could serve as a microenvironment for cell cultures. This microbioreactor stimulates cell coalescence and 3D aggregation while providing optimal gas exchange between the interior and the surrounding environment. Moreover, the properties of liquid marble microbioreactors render them ideal for co-culture experiments. This liquid marble technique has been previously explored and optimized for other cell types. Here we describe a protocol that allows for the derivation of functional cardiac mini organoids, consisting of co-cultured cardiomyocytes and cardiac fibroblasts. These cardiospheres can be valuable for modelling cardiac diseases in vitro and assessing cell interactions to decipher disease mechanisms.
Lab website: https://www.medicalcellbiologylab.com/
Contact: https://www.researchgate.net/profile/Jeffrey-Aalders
RE-place database: https://www.re-place.be/method/liquid-marbles-cost-effective-platform-generate-cardiospheres-co-cultured-cardiomyocytes-and
Projects and initiatives
Transition Project towards Animal-free Innovations
Animal-free innovations are emerging at a fast pace. TPI Chair Daniela Salvatori, and TPI ambassadors Jeffrey Beekman and Elly Hol, explain why animal-free innovations are important and how TPI supports researchers in finding or developing animal-free methods for their research. They call for collaboration.
Projects and initiatives
HealthToxicologyIn vitro
PrecisionTox: transforming chemical safety assessment
In order to better protect human health and the environment from harmful chemicals, the European chemical agency (ECHA) pursues the objective of "zero tolerance" on non-compliance of chemical registration applications. In this video, scientists of the PrecisionTox project - an EU-funded project aiming to accelerate chemical safety assessment with 3Rs compliant models - explain how New Approach Methods (NAMs) provide rich biological data that can help close the data gap to increase acceptance of chemicals dossier while reducing, replacing and refining animal experimentation.
Innovation examples
ToxicologyIn vitro
Stem cell differentiation assays for animal-free developmental neurotoxicity assessment
Victoria de Leeuw was a PhD candidate in the research group of prof. dr. Aldert Piersma at the RIVM and Institute for Risk Assessment Sciences at Utrecht University. Piersma's lab studies the effects of compounds on development of the embryo during pregnancy with, among other techniques, stem cell cultures. The project of Victoria was aimed to differentiate embryonic stem cells of mouse and human origin into neuronal and glial cells, which could mimic parts of differentiation as seen during embryonic brain development. These models were able to show some of the known toxic mechanisms induced by these compounds, congruent with what they we hypothesised to mimic. This provides mechanistic information into how chemical compounds can be toxic to brain development. Therefore, these two stem cell assays make a useful contribution to the animal-free assessment of developmental neurotoxicity potential of compounds.
Victoria is nominated for the Hugo van Poelgeest prize 2022 for excellent research to replace animal testing.
Innovation examples
HealthInnovationIn silico
Using data and computational modelling in biomedical research
Bioinformatics and systems biology hold great promise to translate the wealth of biological data into meaningful knowledge about human health and disease. The group of Bas Teusink helps biologists to deal with high throughput data, for example metabolomics (how cell metabolism works) and proteomics (how protein networks work) from patient material or cell cultures. This can help to better understand disease mechanisms and aid drug targeting or personalised medicine. In the future, combining data from different models (in vitro, in vivo and human data) could become a digital model of humans, or a “ digital twin”.
Click on the link in the video to watch more or read the interview with Bas (and Jaap Heringa) he[https://vu.nl/en/research/more-about/using-data-and-computational-modelling-in-biomedical-research]re.
Projects and initiatives
HealthInnovationPolicyBeginner
We all want a safer world for humanity, animals and the environment: Transition Animal-free Innovation
Why is the transition to animal-free research so important? What are animal-free models? How does TPI (Transition Animal-Free Innovation) encourage their development and use? And who are we working with to make this happen? We explain this in our animation.
More and more animal-free tests and research methods are becoming available, but not all research questions or safety tests can be answered in this way yet. In addition, the validation, qualification and acceptance of non-animal innovations still lags behind. Therefore, the Dutch Ministry of Agriculture, Nature and Food Quality (LNV) stimulates the development and application of animal-free innovations. This is done with the partner programme Transition Animal-free Innovation (TPI).