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Innovation examples
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.).
Innovation examples
Developmental neurotoxicity testing using stem cells
Children should grow up in a safe and healthy environment. Disruption of brain development may have enormous impact on future life and might result in disorders such as ADHD or cognitive decline. The effect of compound exposure on the developing brain is largely unknown, since in the current regulatory test procedures in experimental animals effects on the brain are rarely investigated and human relevance of these animal models is under debate.
Researchers at RIVM are developing a cell model based on human stem cells that mimics a small part of the developing brain. This method is human-relevant, animal-free, and based on mechanistic knowledge of human biology and physiology of brain development. The model can be an important component in a testing strategy to test the safety of chemicals and pharmaceuticals on the developing brain.
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.
Various subjects
InnovationPolicy
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.
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/ .
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.
Expert interviews
HealthInnovation
Elly Hol (UMC Utrecht): possibilities for neuroscience
Prof. dr. Elly Hol (neuroscientist) talks about the opportunities for conducting animal-free research in Utrecht. She explains why it is necessary to use animal models next to cell-based models, for example for her Alzheimer research.
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
ToxicologyInnovationIn vitro
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
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
Policy
Charlotte Blattner (Harvard Law School)
Charlotte Blattner (Harvard Law School, Animal Law & Policy Program)
Innovation examples
HealthInnovationIn vitro
FirstbaseBIO - human brain organoids for studying neurological diseases
Human neurological diseases are still poorly understood, amongst others because animals are used as a model for the human brain. A way to overcome this problem is to mimic human brain functioning in a dish with organoids. FirstbaseBIO is developing off-the-shelf brain organoids on which neurological diseases can be studied. This 3D platform will be formed by reprogrammed human cells from easily accessible sources, for example urine, skin, or mucosa. The proof of-concept brain organoids will be those from patients who are suffering from adrenoleukodystrophy (ALD), a rare, incurable brain disease that occurs primarily in young boys and is often fatal. With the brain organoid platform, possible medicinal treatments for ALD can be effectively optimised.
FirstbaseBIO was nominated for the Venture Challenge 2021 for their development of human brain organoids to study neurological diseases.