Experts
Expert interviews
Innovation
The 3Rs Centre Utrecht: connecting the 3Rs and the NAMs
This animation of the 3Rs Centre Utrecht shows the differences, but also the similarities, between the 3Rs (Replacement, Reduction, Refinement of animal testing) approach and the NAMs (New Approach Methodologies) approach when trying to replace or reduce experimental animal use.
Expert interviews
HealthInnovationPolicy
Stichting Proefdiervrij: Collaboration is key
At Stichting Proefdiervrij (the Dutch society for the replacement of animal testing) we believe that collaboration is essential for the development and implementation of animal-free models. In this video we introduce a few of the ways in which we, as an NGO, collaborate with researchers to reach our goal: the complete replacement of all test on animals
Expert interviews
HelpathonsPolicy
Monique Janssens: Why we need the Transition towards Animal-free Innovations
Why is there a Transition towards Animal-free Innovations, while we have the 3Rs, including Replacement? Well, there is a difference. Animal experiments should no longer be the golden standard of reference. We should not ask: Is this animal-free method good enough to replace animal experiments? But: What is the research question, and how do I get the best answer, preferably without animals? I know that many researchers are doing this already. But we can do even more! It’s also about involving the full chain of parties, including patients, financers, legislators and companies. That is why the transition movement works with interdisciplinary networks and Helpathons. The transition helps to innovate, to accelerate and to implement. At the same time, there is no need to throw the 3Rs overboard. Actually, we owe applying them to the lab animals of today. But by innovating we can develop even more new practices in research and education that bring about better results for science in less time and often with less costs. Without using animals.
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.
Innovations
Innovation examples
HealthIn vitro
Cultured human skin for burn research
Burns are often accompanied by a dysregulated immune response, which can lead to systemic inflammation, impaired immunity, and excessive scarring. A deeper understanding of the mechanisms behind burns—where wound healing and inflammatory reactions are severely disrupted—holds the key to improving patient outcomes. Patrick Mulder, a postdoctoral researcher at the Burn Research Lab in Beverwijk, the Netherlands, works with his colleagues to develop animal-free skin models based on human cells and patient-derived tissues. Using these innovative, human-relevant models, he aims to provide greater insight into the body’s response to burns and studies the effects of existing and new treatments on wound healing.
Click on the info button for the full version of the video.
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.
Innovation examples
HealthIn vitro
Organoids for studying (personalised) antiviral treatments
Giulia is a scientist in clinical virology with a PhD from OrganoVIR Labs at Amsterdam UMC. Her research aims to improve antiviral testing using human organoids—tiny, lab-grown tissues that mimic real human organs. The COVID-19 pandemic highlighted the urgent need for effective antiviral treatments, as traditional pre-clinical testing on animal models has only a 5% success rate in clinical trials. By utilising human organoids, Giulia enhances the accuracy of antiviral research. She specializes in infecting organoids from the airway, gut, and brain with various patient-derived viruses, allowing for more realistic modelling of viral infections. Her work also sets the stage for personalised medicine in the context of viral infections. By isolating viruses and stem cells from patients suffering from severe infections, she can test tailored treatments that are more likely to succeed. With this, she aims to revolutionise antiviral testing and improve treatment outcomes for patients.
Click on the info button for the full version of the video.
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.
Questions
Questions
HelpathonsHealth
Helpathon #11 – Can you help Terry?
Terry Vrijenhoek (UMC Utrecht) is a geneticist and explores the societal impact of gene therapy. In this Helpathon the focus is on Alzheimers, for which there is no cure but there is a promising RNA-based therapy in the pipeline. Can you help Terry with designing scenarios for responsible development for gene therapy for Alzheimer disease in terms of benefits, risks, budgets and animal models? More information can be found here (https://www.helpathonhotel.org/coming-up).
Questions
HelpathonsHealth
Helpathon #11 – Can you help Francesca?
Francesca Stillitano (UMC Utrecht) is a geneticist and an Assistant Professor at the Department of Cardiology. Francesca is currently working with mice models and with human tissue-based in vitro models to develop and test new gene therapies for a rare cardiomyopathy. Can you help Francesca with developing gene therapies for curing inherited cardiomyopathies without the use of animal models? More information can be found here (https://www.helpathonhotel.org/coming-up).
Questions
HelpathonsEducation
Helpathon #10 – Can you help Jolanda and Elza?
Jolanda van der Velden, Chair of Physiology, and Elza van Deel, Educator, from Amsterdam University Medical Center want to support PhDs in preparing for the animal-free transition. They are both looking for an implementation strategy and course design. Do you have an interest in animal-free education and education about animal-free research? Read more and register here (https://www.helpathonhotel.org/coming-up).
Questions
HealthInnovationIn vitro
Helpathon #9 – Can you help Juan?
Juan is an experienced immunologist and scientific director of the cutting edge O2Flow facility for cytometry and cell sorting at the Amsterdam VU University Medical Center. Can you help Juan explore if and how he can transition his facility towards animal free antibodies?
Are you using antibodies in your research do you want others to help you find animal free alternatives for your specific research let us know. More information can be found [here] (https://www.helpathonhotel.org/coming-up).
Projects and initiatives
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
HealthIn vitro
CONNECT
Many people worldwide suffer from brain diseases. These diseases are often hard or even impossible to treat. One of the reasons for this that potentially beneficial drugs cannot pass through the blood-brain barrier. The CONNECT project aims to develop a blood-brain barrier model and connect this to a brain model, all derived from cells. With this advanced in vitro test system, researchers aim to be able to study how drugs can be transferred more effectively and safely over the blood-brain barrier in an animal-free and human-relevant manner.
Projects and initiatives
HealthToxicologyInnovationIn vitro
Cells4Thought: using iPSCs for neurodevelopmental health
The prevalence of neurodevelopmental disorders (NDDs), including cognitive impairments, is increasing worldwide with great impact on daily life quality. There is evidence that exposure to chemicals may contribute to the incidence of NDD. However, a causal link is lacking. Towards this goal, a human-relevant in vitro model system mimicking parts of brain development, such as neuronal network functioning, could be used for mechanistic research on how gene-environment interactions contribute to the development of NDD. This is going to be studied in the project Cells4Thought, using induced pluripotent stem cells form different individuals to study the effect of chemicals on neuronal differentiation.
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).
Meetings & conferences
Meetings & conferences
HelpathonsHealthToxicologyIn silico
ONTOX Hackathon: Hack To Save Lives And Avoid Animal Suffering
Artificial Intelligence (AI) in toxicology – a potential driver for reducing or replacing laboratory animals in the future. ONTOX project is looking for solutions and innovative ideas to move forward. Are you going to help ONTOX to hack into these complex challenges?
The hackathon will be held from 21 to 23 April 2024 in Utrecht Science Park. The whole event is open to a diverse community of forward-thinkers and problem-solvers interested in the intersection of AI and ethical toxicology. The goal is to bring together passionate individuals who seek innovative solutions to critical challenges in toxicology.
Read more about the hackathon and register here (https://ontox-project.eu/hackathon/).
Meetings & conferences
HealthInnovationPolicy
Debate about animal testing
Animal testing contributes to advances in medicine and science in general. But in recent years people have increasingly questioned research using laboratory animals. The European Union and the Dutch government want to be a forerunner in the development and use of innovations that do not involve animal testing, but how do we want to achieve that? What are the challenges and opportunities for biomedical sciences? How do we accelerate the transition towards animal-free innovation? And what does this mean for research into better treatments for animals? In this debate Dutch leaders in the field of animal(-free) testing share their thoughts and opinions.
Meetings & conferences
HealthIn vitroAdvanced
A 3D melanoma for the development of skin cancer treatment
The developing process of a new drug, from first testing to regulatory approval and ultimately to market is a long, costly, and risky path. Noteworthy is the fact that almost 95% of the drugs that go into human trials fail. According to the National Institutes of Health (NIH), 80 to 90% of drug research projects fail before they ever get tested in humans. The value of preclinical research, mainly conducted in animal model experiments for predicting the effectiveness of therapies and treatment strategies in human trials, has remained controversial. Only 6% of the animal studies are successfully translated into the human response. Breaking down failure rates by therapeutic area, oncology disorders account for 30% of all failures. The absence of human-relevant models with receptors, proteins, and drug interactions in the in situ microenvironment leaves a gap in the scientific discovery process of new therapies. In this context, the present work presents the development of a sophisticated in vitro skin model platform focus on boosting melanoma treatment. The results showed a physiological microenvironment of human skin with epidermal differentiation and development of stratified layers (basement membrane, stratum spinosum, stratum granulosum, and stratum corneum). Furthermore, it was observed the pathophysiological microenvironment of the melanoma with invasion or migration through the basement membrane into the dermis and no epidermal differentiation. Vemurafenib treatment, the gold standard which targets BRAF mutations, showed a decrease in proliferation and invasion of melanoma tumors, with an increase in epidermis keratinization. Melanoma incidence continues to increase year-on-year and is currently responsible for >80% of skin cancer deaths. It is the most common cutaneous form and is known to have the highest mutational load of all cancers. Nowadays, patients with advanced melanoma BRAFV600E mutation can benefit from monotherapies or targeted therapies. Although the initial response rate is effective, disease progression and tumor chemoresistance rapidly occur in the majority of patients. Therefore, the treatment of melanoma remains a challenge, and despite the advances, there is still an urgent need to identify new therapeutic strategies. 3D Model Melanoma is considered one important tool for studying the evolution of the pathology, as well as evaluating the effectiveness of new therapeutic approaches.
Meetings & conferences
HealthIn vitroAdvanced
3D tumor models for CAR-T-cell therapy optimization
Chimeric antigen receptor (CAR) T-cell therapy accounts for one of the most promising therapeutic advances in cancer immunotherapy. In this form of adoptive cell transfer, T-cells of a patient are engineered to express so-called ‘CARs’, in which the antigen-recognition capacity of antibodies is combined with T-cell activating domains. So far, CAR-T-cell therapy obtained its most impressive results in hematological malignancies resulting in the approval of five CAR-T cell products by the FDA for hematologic indications. However, CAR-T-cell therapy has not mirrored its success in solid tumors. The poor efficacy of CAR-T-cell therapy in solid tumors has, in part, been attributed to the lack of understanding in how CAR-T-cells function in a solid tumor microenvironment. Classical validation methods rely on the use of specificity and functionality assays in 2D models against adherent target cells or target cells in suspension. Yet, by using these models, observations made in vitro may differ greatly to an in vivo situation where tumors are engrafted in 3D structures. We developed a more relevant and translational 3D tumor model using eGFP+ target cells. This allows us to couple 3D tumor cell killing by CAR-T-cells to live-cell imaging, providing an efficient quantification of target cell death. As proof- of-concept, we used a 3D model of eGFP+ glioblastoma cells and CAR-T-cells targeting a pan-cancer antigen. This 3D glioblastoma model allowed us to show that classical scFv-based CAR-T-cell therapy of glioblastoma cells can be improved by nanoCAR-T-cells. Furthermore, combining nanoCAR-T-cell therapy with a genetic approach of nanobody-based anti-PD-L1 immune checkpoint blockade further increased the cytotoxicity of the nanoCAR-T-cell therapy.
TPI.tv videos
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.
TPI.tv videos
Five simple tricks for making your own video for TPI.tv
This video shows you how to make a video yourself. It's really not that difficult! See also the submission page (https://tpi.tv/submit-a-video) for additional information.