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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
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 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
In vitro predictive models of particle-induced granulomas
Léa Hiéronimus is a PhD student at the Louvain centre for Toxicology and Applied Pharmacology (LTAP, UCLouvain, Belgium). Léa is working in François Huaux's team, where we are trying to better understand how certain inhaled particles exert their toxicity. The goal is to better diagnose and treat individuals exposed to particles, but also to identify the particle characteristics which induce, or do not induce, toxic effects. For this, Léa studies a very particular cell type which seems to be involved in particle responses. Indeed, we have found the specific accumulation of the innate subset of B-lymphocytes called “B-1 lymphocytes”, which occurred during granuloma formation/maturation induced by inhaled particles in mice. According to the literature, this accumulation can be attributed to their migration from mesothelial cavities such as the peritoneum, acting as a reservoir.
In addition to conventional particles-induced granulomas, which formation rely on macrophages responses, we developed new models relying on B-1 lymphocytes. Indeed, B-1 lymphocytes show a unique clustering property, that is not observed using macrophages or other subsets of B-lymphocytes (conventional B-2 lymphocytes) as purified B-1 lymphocytes regroup granuloma-inducing particles (carbon nanotubes CNT7, crocidolite asbestos, micrometric silica MinUSil and MSS, cobalt oxide,…) but not carbon black, a particle not-inducing granuloma in vivo. Additionally, we developed a model aiming to recapitulate the lung after B-1 lymphocytes migration and found that macrophages and epithelial cells (MHS and LA4 cell lines) where grouped to form spheroids when in coculture with B-1 and not B-2 lymphocytes.
These models will serve as tools to identify new mediators of granuloma formation, which could serve as biomarkers and/or therapeutic targets for exposed individuals. On the other hand, we aim to propose new bioassays for the prediction of granuloma-inducing materials using alternative models.
Lab website: https://uclouvain.be/en/research-institutes/irec/ltap
Contact: lea.hieronimus@uclouvain.be
Projects and initiatives
The Beyond Animal Testing Index
The Beyond Animal Testing Index (BATI) was designed after the Access to Medicine Index with the aim to be a transparent, objective and independent benchmark that provide public research organisations and their stakeholders insight in what efforts and contributions they make in the transition to animal free innovation and to provide organisations incentive to learn from and inspire each other with regard to the implementation of research practices without the use of animals for the benefit of science.
Innovation examples
HealthIn vitroOrgan-on-Chip
Tumor-on-chips to study delivery of protein therapeutics
Valentina is a PhD candidate at the Department of Biochemistry at Radboudumc. Her research focuses on developing and applying organ-on-chip technologies, such as tumor-on-a-chip systems, to study the tissue-specific and cytosolic delivery of protein therapeutics. Valentina's research has also aimed at bridging the gap between engineers and biologists, promoting the use of microfluidic organ-on-chip technologies to answer more relevant biological questions. One example of this is the development of a mathematical model that could be applied to study drug delivery and diffusion in a tumor-on-a-chip system and to extrapolate possible outcomes of the delivery of therapeutic proteins to tumors in the human body. Another collaboration led to the development of a tumor-on-a-chip where hypoxic conditions can be replicated and investigated, and where the targeting of specific hypoxia markers in tumor cells can be investigated.
Questions
HealthInnovationIn vitro
Helpathon #8 – Can you help Germaine?
Germaine Aalderink is investigating the uptake of lipids travelling from the gut into the lymphatic system and further explore the merits of this alternative drug intake strategy. Can you help Germaine make an intestinal and lymphatic model with an alternative for Matrigel that is animal-free? She wants to know what components are essential in each phase of intestinal development and is interested in both the positive and negative experiences of other researchers with the use of alternatives for Matrigel.
Click on the link in the video to sign up and read more information on this Helpathon on the website (https://www.helpathonhotel.org/coming-up).