Helpathon #4 - can you help Raissa?
Can you help Raissa find a more complex organoid-like brain and immune model based on rhesus microglia to study aging in relation to neuroinflammation and neurodegenerative diseases? Join Helpathon #4, look at www.tpihelpathon.nl/coming-up ! Raissa Timmerman is a PhD student at the alternative unit at the Biomedical Primate Research Center. A better understanding of aging of the brain is key to studying neuroinflammation and neurodegenerative diseases. We believe there is a potential for breakthrough in using our existing live macaque data obtained from past aging experiments to develop more complex in vitro rhesus brain-like models and then to correlate all this data with data from human in vitro models and human live data.
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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
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
Transition Project towards Animal-free Innovations
Animal-free innovations are emerging at a fast pace. TPI Chair Daniela Salvatori, and TPI ambassadors Jeffrey Beekman and Elly Hol, explain why animal-free innovations are important and how TPI supports researchers in finding or developing animal-free methods for their research. They call for collaboration.