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Expert interviews
HealthIn vitro
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: biomedicals@upm.com.
Innovation examples
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.
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
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.
Innovation examples
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
Expert interviews
Education
Glenn Embrechts (European Schoolnet)
Skills in Science, Technology, Engineering and Mathematics (STEM) are becoming an increasingly important part of basic literacy in today's knowledge economy. European Schoolnet is at the forefront of the debate on how to attract more people to science and technology to address the future skills gap that Europe is facing. STEM is one of European Schoolnet's major thematic domains. We have been involved in more than 30 STEM education initiatives, financed through European Schoolnet's Ministry of Education members, industry partners, or by the European Union's funding programmes. More information on social media: Social media: https://m.facebook.com/labonderwijs and https://www.instagram.com/lab_gedrevenonderwijs/ .
Expert interviews
Policy
Charlotte Blattner (Harvard Law School)
Charlotte Blattner (Harvard Law School, Animal Law & Policy Program)
Expert interviews
HealthToxicology
Kirsten Baken (VITO)
Kirsten Baken (VITO, www.vito.be) discusses biomonitoring as part of the HBM4EU project (www.hbm4eu.eu). An example of the use of human biomarkers can be found at https://www.sciencedirect.com/science/article/pii/S0013935119302658 .
Conferences abstracts
Optimizing CAR-T-cell therapy using 3D tumor models and real-time cell imaging
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.
Innovation examples
Understanding implant safety in vitro
Each year, millions of people receive an implant. The function of damaged tissues or organs is successfully restored in most people, however, some do develop complications. The safety of medical devices is indicated for legislation using international regulations. In the relevant standards, tests mainly focus on the chemical nature of the implants using classical toxicological end-points. However, more recently we have learned that the mechanical forces from an implant on the host-tissue can have significant effects on the host-response as well. At RIVM we want to develop an animal-free model that better resembles the interface between the implant and the host-tissue, and by updating the testing strategies contribute to implant safety on the long term.
Expert interviews
ToxicologyIn vitro
Erwin Roggen (ToxGenSolutions)
ToxGenSolutions provides a cutting-edge patchwork of test methods required for modern testing and assessment of compounds and products. It builds on a virtual generic platform of leading test and technology developers providing novel technologies addressing key events in outcome pathways. ToxGenSolutions products are proprietary mechanism-based gene signatures for identification and classification of toxicants during screening, product development and safety assessment. More information on https://toxgensolutions.eu/ .
Innovation examples
HealthInnovation
Whole blood assessment of thrombosis tendency
Transgenic animals are often subjected to short and long term experimental models of thrombosis and atherosclerosis with considerable discomfort to the animal. This project aims to: 1) replace (human blood instead of animal blood), 2) reduce (a few drops of blood per test), and 3) refine (replace in vivo by in vitro testing with isolated blood) the use of laboratory animals with two new small blood volume function tests—the perfusion chamber and the thrombin generation test. Both tests will be equipped with a simple detection capability, which is affordable for laboratories. Their application is not only in the field of thrombosis and haemostasis but also for the investigation of other blood-related diseases, such as arteriosclerosis, diabetes and cancer. By Sanne Brouns (Department of Biochemistry CARIM, Maastricht University, the Netherlands) and Linda Herfs (Flowchamber B.V.).