Popular
Innovation examples
New approaches for cancer hazard assessment
Chemical substances are subjected to assessment of genotoxic and carcinogenic effects before being marketed to protect man and the environment from health risks. For cancer hazard assessment, the long-term rodent carcinogenicity study is the current mainstay for the detection of nongenotoxic carcinogens. However, carcinogenicity studies are shown to have prominent weaknesses and are subject to ethical and scientific debate. A transition toward a mechanism-based weight of evidence approach is considered a requirement to enhance the prediction of carcinogenic potential for chemicals. At RIVM, we are working on this alternative approach for cancer hazard assessment, which makes optimal use of innovative (computational) tools and be less animal demanding.
For more information, click on the link in the video or read on here (https://doi.org/10.1080/10408444.2020.1841732) and here (https://doi.org/10.1080/10408444.2018.1458818).
Contact the expert (https://nl.linkedin.com/in/mirjamluijten)
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
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.
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.
Projects and initiatives
SCREENED
The European collaborative project SCREENED aims to develop three-dimensional (3D) cell-based in vitro tests to better characterize the effects of endocrine disruptors (EDs) on thyroid gland function. This method will overcome the limitations of existing tests, being more sensitive at low doses of exposure to chemicals, and enabling the prediction of their toxicity on human health in a sex-specific manner. The ambition of the SCREENED project is that these new 3D in vitro tests, as well as the increased knowledge about adverse reactions after exposure to EDs, will be used for regulatory purposes, ultimately to improve human health.
Innovation examples
HealthInnovationIn vitro
Using skin and mucosa models to replace animal testing
The skin and mucosa are important tissues that differ between species in health and disease. The group of Sue Gibbs works on the development of advanced in vitro models that mimic these two tissues, specialising in immunity models and organ-on-a-chip technologies. They use skin models to study for example melanoma, skin allergies, eczema, burns and healing wounds. Dental models are used for the safety of materials used in dentistry, for example to test the quality of the implant and false tooth when it comes to attaching to the soft tissue. Their ambition is to expand into the field of multi-organ technology to make even more relevant models for the human skin and mucosa.
Click on the link in the video to watch more or read the interview with Sue he[https://vu.nl/en/research/more-about/using-skin-and-mucosa-models-to-replace-animal-testing]re.
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
Policy
Charlotte Blattner (Harvard Law School)
Charlotte Blattner (Harvard Law School, Animal Law & Policy Program)
Expert interviews
HealthEducation
Daniela Salvatori: TPI Utrecht
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.
Conferences abstracts
Liquid marbles: a cost-effective platform to generate cardiospheres from co-cultured cardiomyocytes and cardiac fibroblast for disease modelling
Advances in three-dimensional (3D) culture techniques have shown several advantages over 2D cultures, especially by more accurately mimicking the in vivo environment. This has led to improved reproducibility and reliability of experimental results, which are important criteria in disease modelling and toxicity testing. Induced pluripotent stem cells (iPSC) provide an unlimited source for the derivation of all cell types of the adult body, including cardiomyocytes. To improve the current culture methods for multicellular cardiac spheroids, such as the hanging drop method, we explored the use of hydrophobic powders. Fumed silica nanoparticles can be used to encapsulate liquid drops, which could serve as a microenvironment for cell cultures. This microbioreactor stimulates cell coalescence and 3D aggregation while providing optimal gas exchange between the interior and the surrounding environment. Moreover, the properties of liquid marble microbioreactors render them ideal for co-culture experiments. This liquid marble technique has been previously explored and optimized for other cell types. Here we describe a protocol that allows for the derivation of functional cardiac mini organoids, consisting of co-cultured cardiomyocytes and cardiac fibroblasts. These cardiospheres can be valuable for modelling cardiac diseases in vitro and assessing cell interactions to decipher disease mechanisms.
Lab website: https://www.medicalcellbiologylab.com/
Contact: https://www.researchgate.net/profile/Jeffrey-Aalders
RE-place database: https://www.re-place.be/method/liquid-marbles-cost-effective-platform-generate-cardiospheres-co-cultured-cardiomyocytes-and
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/ .