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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
Projects and initiatives
HealthToxicologyIn vitroIn silico
VHP4Safety project
The safety testing of chemicals and pharmaceuticals traditionally relies on animal studies. However, these raise ethical concerns and often fail to accurately predict human responses. New scientific developments offer opportunities to build a Virtual Human Platform (VHP) for safety assessment, a platform that enables assessment based solely on human physiology and biology, integrating data from in vitro and in silico models. This video explains how we are developing the VHP through an interdisciplinary approach. Read the paper in the videolink or visit or VHP4Safety (https://vhp4safety.nl/) for more information.
Projects and initiatives
HealthToxicology
The NAM Navigator: A unique repository for information on the validation and acceptance of New Approach Methodologies
The NAM navigator is an innovative knowledge portal to navigate you to and through valuable information on the development, standardization, validation and acceptance of New Approach Methodologies (NAM). The NAM Navigator acts as an online guide that provides specific information needed in each of these steps, thereby increasing the broad use of animal-free innovations. Follow the link in the video to start navigating!
Innovation examples
HealthIn vitroOrgan-on-Chip
Using skin and mucosa models to replace animal testing
The skin and mucosa are important tissues that differ between species in health and disease. The group of Sue Gibbs works on the development of advanced in vitro models that mimic these two tissues, specialising in immunity models and organ-on-a-chip technologies. They use skin models to study for example melanoma, skin allergies, eczema, burns and healing wounds. Dental models are used for the safety of materials used in dentistry, for example to test the quality of the implant and false tooth when it comes to attaching to the soft tissue. Their ambition is to expand into the field of multi-organ technology to make even more relevant models for the human skin and mucosa.
Click on the link in the video to watch more or read the interview with Sue he[https://vu.nl/en/research/more-about/using-skin-and-mucosa-models-to-replace-animal-testing]re.
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
ToxicologyIn vitroOrgan-on-Chip
Human pluripotent stem cell derived cardiomyocytes for disease modelling and drug discovery
Berend van Meer did his PhD research in the research group of prof. Christine Mummery at the department of Anatomy and Embryology of the Leiden University Medical Center. In this group, human pluripotent stem cell derived (Organ-on-Chip) models are being developed, mostly cardiovascular models. The work of Berend aimed to understand how well these stem cell based cardiac models can predict the effect of (well-known) drug therapies in patients. Importantly, the outcomes of the experiments were compared to very similar measurements in rabbit heart muscle cells. And while animal models predicted less than 70% correctly, the human stem cell based models predicted almost 80% of the expected effects correctly. The research contributes to understanding the relevance of stem cell based models and strengthens the confidence regulators and pharmaceutical companies have in such models as animal alternatives in the drug development pipeline.
Berend van Meer has won the Hugo van Poelgeest prize 2020 for his research on human pluripotent stem cell derived cardiomyocytes for disease modelling and drug discovery.
Christine Mummery's lab on Heart on Chip, Disease modeling and toxicity: https://www.lumc.nl/org/anatomie-embryologie/research/902040935402533/
Innovation examples
ToxicologyIn vitroOrgan-on-Chip
Cartilage-on-a-chip for studying joint degenerative diseases
Carlo Alberto Paggi is currently a PhD candidate at the University of Twente in the research group of Prof. Marcel Karperien and Prof. Séverine Le Gac. Karperien’s lab focus on the biological aspects of osteoarthritic research while Le Gac’s specialize in organ-on-chip development. The project of Carlo Alberto is developing a joint-on-chip platform to create a reliable in vitro model to study disease progression in osteo- or rheumatoid arthritis. The model combines different organ-on-chips aimed at replicating each a tissue around the joint such as cartilage, bone and ligaments. This new technology focuses on better reproducing human models and at substituting the use of animal models for drug research. If you want to know something more about the project and the groups, you can follow the link in the video.
Carlo Paggi was nominated for the Hugo van Poelgeest prize for his research on a cartilage-on-a-chip model to study joint degenerative diseases
Karperien’s lab of Developmental Bioengineering: https://www.utwente.nl/en/tnw/dbe/
Le Gac’s lab of Applied Microfluidics for BioEngineering Research: http://www.severinelegac.com/
Linkedin: https://www.linkedin.com/in/carlo-alberto-paggi-76500b135/
Innovation examples
HealthToxicologyIn vitro
Assessing respiratory toxicity using in vitro models
The airways form a barrier for inhaled compounds, however, such compounds may cause local effects in the airways or may lead to lung diseases, such as fibrosis or COPD. Cell models of the respiratory tract, cultured at the air-liquid-interface (ALI) are a relevant model to assess the effects of inhaled compounds on the airways. Such models allow human relevant exposure, which is via the air, and assessment of effects on the epithelial cell layer. At RIVM we use air-liquid-interface cultured cell models and expose these to airborne compounds to assess the effects of agents such as nanomaterials, air pollutants or compounds from cigarette smoke. By using a mechanism-based approach to assess the effects of these compounds we invest in animal-free alternatives that better predict adverse effects in humans.
Innovation examples
In vitroOrgan-on-Chip
Unified organoid system for modeling heart and kidney interaction on-a-chip
Beatrice Gabbin is a PhD candidate at the Anatomy and Embryology Department of the Leiden University Medical Center. Her project is shared with the Nephrology Department and focusses on the study of the cardiorenal axis in vitro. Both heart and kidneys have vital functions in the human body and reciprocally influence each other’s behavior: pathological changes in one can damage the other. There are already multiple independent in vitro (human) models of heart and kidney, but none have so far captured their dynamic crosstalk. The aim of the project is therefore to develop a microfluidic system which can be used to study heart and kidney interaction in vitro. For this purpose, cardiac microtissues and kidney organoids derived from human induced pluripotent stem cells are generated and loaded onto a 3D perfusion chip for their dynamic co-culture. This system enables the study the cardiac and kidney interaction with a high level of control. The validation of a unified organoid system will enable the investigation of diseases involving the two organs and their potential treatments. Read more via the link in the video and https://doi.org/10.1016/j.mtbio.2023.100818.
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.
Expert interviews
Policy
Charlotte Blattner, Harvard Law School: Transition needs community efforts
Charlotte Blattner is a visiting researcher at Harvard Law School on the Animal Law & Policy Program and explains that a transition is needed to move away from animal testing. This transition needs to be a just transition, a community effort where all stakeholders are involved to replace animal testing for animal-free innovations.
Expert interviews
HealthToxicologyIn vitro
Erwin Roggen, ToxGen Solutions: Applying animal free testing approaches
Erwin Roggen explains his role as pioneer in the development of technologies for animal-free application. His product, ToxGenSolutions, provides test methods required for modern testing and assessment of compounds and products. It builds on a virtual generic platform of leading test and technology developers providing novel technologies addressing key events in adverse outcome pathways.