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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
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.
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.
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.
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/
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
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
HealthToxicologyIn silico
Developing a computational model for human neural tube closure
Animal-free methods for human chemical safety assessment are promising tools for the reduction of animal testing. However, these methods only measure a small aspect of biology compared to an in vivo test. The reductionist nature of these methods thus limits their individual application in the regulatory arena of chemical risk assessment. Ontologies can be used to describe human biology, and delineate the basis of adverse outcome pathway networks that describe how chemical exposures may lead to adverse health effects. This pathway description can then help to select animal-free in vitro and in silico methods, comprehensively covering the network. The comprehensiveness of this approach, firmly rooted in human biology, is expected to facilitate regulatory acceptance of animal-free methods. As an example, this video zooms in on the development of a computational model for neural tube development, an aspect of human development that is especially vulnerable to chemical disruption.
This research is part of the ONTOX project (https://www.ontox-project.eu).
For more information on the concept of the Virtual Human, click here (https://doi.org/10.1016/j.cotox.2019.03.009.).
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)
Projects and initiatives
HealthInnovationPolicy
EURL ECVAM
The EU Reference Laboratory for alternatives to animal testing (EURL ECVAM) promotes and facilitates the use of non-animal methods in testing and research. It validates, disseminates and shares knowledge on the 3Rs (Replacement, Reduction and Refinement of animal experiments). In this video, Raffaella Corvi explains what EURL ECVAM does in the field of safety testing of chemicals while reducing laboratory animal testing.
Watch the accessible version of the video here (https://audiovisual.ec.europa.eu/en/video/I-230374).
©European Union, 2021
Projects and initiatives
HealthToxicologyIn vitro
RISKHUNT3R project – interview by TOXstreams
Many studies are focused on finding the next best tool or test to assess the risk associated with chemical exposure. That is all well and good, but even the perfect assay needs to be accepted by regulators before seeing the light of the day. And how do we do that? The guests in this webinar have some ideas on that as principal investigators of the EU project RISK HUNT3R. Prof. Bob van de Water, Dr Mirjam Luijten and Dr Andrew White explain what RISK HUNT3R is doing, what next generation risk assessment means and why it is so important. Click on the link in the video to watch the whole interview.