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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
Innovation examples
HealthToxicologyIn silico
AI agents for safer science: How AI is Changing Chemical Risk Assessment
This video introduces a novel approach to chemical safety, where intelligent digital agents guided by large language models support scientists in making faster, more transparent decisions. By automating complex workflows and integrating tools like the OECD QSAR Toolbox, these agentic systems help prioritise research, reduce reliance on animal testing, and pave the way for safer, more sustainable innovation.
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
In vitroOrgan-on-Chip
From 2D hiPSC culture to developing a 3D vessel-on-chip
Theano Tsikari is a 2nd year PhD student at the Orlova group at LUMC. As part of the LymphChip consortium, her project focuses on the development of immunocompetent organ-on-chip models of the cardiovascular system, and especially the integration of tissue-resident macrophages and lymphatic vasculature using human induced pluripotent stem cells. In this video, you can follow her as she presents you the backbone of her project, a 3D hiPSC-derived vessel-on-chip model, that has been previously developed in the Orlova group and can be employed for the generation of advanced in vitro models of vascular diseases.
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.
Innovation examples
HealthIn vitroOrgan-on-Chip
Stem cell derived Vessels-on-Chip to study brain disorders
Dennis Nahon is a PhD candidate in the Department of Anatomy and Embryology at the Leiden University Medical Center. In his research, under supervision of Dr. Valeria Orlova (https://www.orlovalab.com/) and Prof. Dr. Christine Mummery, he aims to mimic a blood vessel in the brain by combining different stem cell derived cell types, in a 3D Vessel-on-Chip model. Here, an example of these in vitro blood vessels is shown in which certain brain cells known as astrocytes (in white) interact with the blood vessels (in red). This model paves the way for investigating brain vessels outside the human body, while reducing the need for animal models.
Innovation examples
HealthToxicologyIn vitro
Thyroid Hormone & Brain Development: animal-free models for human safety assessment
The environment can have a significant impact on a child's health even before birth. Brain development begins in the first trimester and continues until the age of 25, with thyroid hormone playing a critical role. During early pregnancy, the fetus depends on the mother's thyroid hormone, and a disruption in the thyroid hormone balance can lead to cognitive and motor impairments in the child. As part of the VHP4Safety project, we are developing in vitro tests to measure the developmental neurotoxic effects caused by disturbances thyroid hormone concentrations. Current testing guidelines do not always include testing for neurodevelopmental effects, highlighting the need for new non-animal methods. At the Erasmus Medical Center, human cell lines representing brain cell types are cultured to study the effect of chemicals on the thyroid hormone balance. RIVM uses human stem cells to create neuron-astrocyte networks that mimic brain development. By combining these different assays and models, we are creating a comprehensive human-based testing strategy to assess developmental neurotoxicity. These advances are a critical step toward eliminating animal testing while protecting the health and environment of future generations.
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.
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
Innovation examples
HealthToxicology
New approaches for cancer hazard assessment
Chemical substances are subjected to assessment of genotoxic and carcinogenic effects before being marketed to protect man and the environment from health risks. For cancer hazard assessment, the long-term rodent carcinogenicity study is the current mainstay for the detection of nongenotoxic carcinogens. However, carcinogenicity studies are shown to have prominent weaknesses and are subject to ethical and scientific debate. A transition toward a mechanism-based weight of evidence approach is considered a requirement to enhance the prediction of carcinogenic potential for chemicals. At RIVM, we are working on this alternative approach for cancer hazard assessment, which makes optimal use of innovative (computational) tools and be less animal demanding.
For more information, click on the link in the video or read on here (https://doi.org/10.1080/10408444.2020.1841732) and here (https://doi.org/10.1080/10408444.2018.1458818).
Contact the expert (https://nl.linkedin.com/in/mirjamluijten)
Innovation examples
HealthIn vitroOrgan-on-Chip
Modelling COVID-19-induced thrombosis using blood-perfused Vessels-on-Chips
A subset of hospitalized COVID-19 patients develops severe symptoms like microthrombosis and multiple organ-failure, worsening survival rates. The most inner layer of cells of a blood vessel, the endothelial cells, play a central role in the development of these complications. Their dysfunction can be replicated in advanced cell culture models like our blood-perfused Vessel-on-Chip to further understand disease mechanisms. In this short highlight, Huub Weener from the University of Twente shows how the technique works and what these models contribute to our knowledge of COVID-19.
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.