Transition beyond animal welfare
This video explains what the programme TPI (Transition Programme for Innovation without the use of animals) is about.
Respiratory toxicity using in vitro methods
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.
Tony Kiuru (UPM Biomedicals)
Tony Kiuru discusses GrowDex, which is an animal free, ready to use hydrogel that mimics the extracellular matrix (ECM) and supports cell growth and differentiation with consistent results. Bridging the gap between in vitro and in vivo studies GrowDex can be used for 3D cell culture for spheroid and /organoids, in personalised medicine, regenerative medicine, organ-on-a-chip models, drug release studies, 3D printing and much more. GrowDex hydrogel is manufactured according to ISO13485. You can find more information about GrowDex at https://www.upmbiomedicals.com/siteassets/documents/growdex-brochure-2018.pdf and https://www.linkedin.com/company/growdex/ . General email address: email@example.com.
A hybrid in silico-in vitro cardiorespiratory simulator for medical device testing
Cardiovascular medical devices (CMDs) (e.g. artificial hearts, ventricular assist devices, ECMO, heart valves) support the cardiac and/or the respiratory function of patients. Large challenges are encountered when assessing CMDs interaction with the human body and the effects on the heart and vessels. Especially CMDs with new designs require an extensive evaluation concerning their effectiveness and safety under different pathophysiological conditions. We propose a high fidelity cardiorespiratory simulator for the testing of the hemodynamic performance of CMDs. The proposed simulator merges the flexibility of the in silico system with a hydraulic interface to test CMDs. As such, the simulator embeds a high fidelity cardiorespiratory model, allowing the reproduction of pathologies at both cardiac and respiratory level. The simulator works as a test bench for the assessment of CMDs, from prototype stage to pre-clinical stage. Thanks to its flexibility and high-fidelity, the simulator helps reducing animal testing and provides insights on how to improve CMD design to better suit different patient’s needs. Contact: https://www.kuleuven.be/wieiswie/en/person/00098489 RE-place database: https://www.re-place.be/method/cardiovascular-modelling-medical-device-testing
Platform for in vitro airborne inhalation testing
The air-liquid interface (ALI) technique uses lung cells cultured on a tiny polymer membrane in a cup. On one side of the membrane is a liquid containing the medium necessary for the cells to survive, while the other side is in contact with air. This is similar to the situation in the human lung. The compound to be tested is administered via an aerosol, vapor, or gas to mimic the situation in human lungs. By monitoring different parameters in the cell model before and after the compound is added, it is possible to measure the effects on lung cells. Depending on the test to be carried out, the lung cells can come from different regions in the respiratory tract and even from a variety of people, including individuals who smoke a lot or have specific diseases such as chronic obstructive pulmonary disease or asthma. In vitro ALI inhalation testing (https://doi.org/10.1021/acs.est.7b00493) adds value for e.g. pre-clinical trials and research in the pharmaceutical industry and testing (new) compounds for the chemical sector and beyond. The advantages of ALI inhalation testing are that it is a non-animal method, it reduces the use of in vivo experiments, pre-clinical testing with human-derived cell models is more realistic and limits clinical trial failures and it provides faster and more efficient testing of compound
Animal-free computational modelling for prevention of human chemical-induced neural tube defects
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.).
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).
Helpathon #4 - can you help Frank?
Can you help Frank with integrating an immune system into a macaque lung organoid to address local immunity to tuberculosis with his vaccination strategy? Join Helpathon #4, look at www.tpihelpathon.nl/coming-up ! Frank Verreck does research on tuberculosis at the Biomedical Primate Research Center (BPRC). Tuberculosis is the most deadly infectious disease worldwide! For the past hundred years, BCG (Bacillus Calmette Guérin) vaccinations take place through the skin. Research shows that macaques can be better protected from this infection by vaccination through their lungs. Frank really wants to further study the potential of this alternative vaccination strategy. He wants to understand how this BCG vaccination works in macaques lungs.
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/
GUTS BV - small intestine-on-a-chip and advanced computational analysis for compound and protein screening
GUTS BV is a contract research organization offering its 3-dimensional state-of-the-art small intestinal in vitro model in combination with custom computational analysis approaches. The small intestinal model was developed during Dr. Paul Jochems PhD research at Utrecht University in the group of Prof. Roos Masereeuw. In comparison to the current gold standard (Transwell model), they show improvement in cell differentiation (all major specialized cell types present), physiological structure (3D tube- and villi-like structures) and a functional epithelial barrier. After acquiring experimental data from this model computational analysis approaches are used to score and compare measured compounds for all tested biological parameters at once. The combined effort of improved in vitro modelling and data analysis is believed to result in an enhanced preclinical predictability. GUTS BV was nominated for the Venture Challenge 2021 for their development of an intestinal model combined with advanced computational analysis for protein and chemical compound screening. Research papers: https://www.sciencedirect.com/science/article/pii/S0887233318307811 https://www.mdpi.com/2072-6643/12/9/2782/htm https://www.nature.com/articles/s41538-020-00082-z LinkedIn: https://www.linkedin.com/company/71016128/
Setting up a PDXO platform of pancreatic cancer with spatial -omics characterization
Pancreatic ductal adenocarcinoma (PDAC) is known for its aggressive biology and lethality. Due to a low success rate of current diagnostic and therapeutic approaches in clinic, there is an urgent need for preclinical research studies to investigate the underlying biology of this malignancy. This knowledge is indispensable to facilitate the development and validation of potential new therapeutic compounds. Superior to conventional biomedical research models, the focus of this study is on the development and use of a well-established patient-derived 3D in vivo model, mimicking the tumor as it is present in a human body. The development and characterization of pancreatic cancer derived organoids. This model is extensively analysed using advanced histological methods omics technology to perform tumor subtyping. 15 established PDAC organoid lines and their corresponding parental tumors are validated using immunostainings and DNA hotspot sequencing. This study is the first to show in situ detection of important driver mutations of pancreatic cancer, like KrasG12D, both in parental tumor and organoids. Additionally, specific culture conditions are defined to develop subtype-specific organoids which are validated using multiplex RNA in situ hybridization and transcriptomics. We are proud to collaborate in a fruitful international project, aiming to set-up a pre-clinical screening platform for pancreatic cancer based on patient-derived organoids -and xenografts. Altogether, spatial-omics in depth analysis of both models will demonstrate (1) high resemblance to parental tissue and (2) subtype-specific signatures associated with type of model. Ultimately, the screening platform can be used by pharmaceutical companies to facilitate oncological drug testing in a subtype specific way. Publications Ilse Rooman's lab: https://pubmed.ncbi.nlm.nih.gov/34330784/ https://pubmed.ncbi.nlm.nih.gov/31161208/
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.