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Introduction
I am working on various projects accelerating the transition towards animal-free innovations. In one of the projects we are interested in developing alternatives to animal testing to assess compound-induced developmental neurotoxicity. Our lab currently works with murine and human embryonic and induced pluripotent stem cells that we differentiate into neuronal-astroglial co-cultures. As read-outs we use RNAseq and imaging techniques.
Publications
Publications (20)
Dopamine is present in a subgroup of neurons that are vital for normal brain functioning. Disruption of the dopaminergic system, e.g., by chemical compounds, contributes to the development of Parkinson’s disease and potentially some neurodevelopmental disorders. Current test guidelines for chemical safety assessment do not include specific endpoint...
There is an increased awareness that the use of animals for compound-induced developmental neurotoxicity (DNT) testing has limitations. Animal-free innovations, especially the ones based on human stem cell-based models are pivotal in studying DNT since they can mimic processes relevant to human brain development. Here we present the human neural pr...
While whole animal studies have their place in risk assessment of food and feed components, it is thought that more modern approaches such as human focused new approached methodologies (NAMs) would bring advantages including a greater focus to the human species, a focus on molecular mechanism and kinetics and the possibility of addressing susceptib...
Chroom-6 en medische implantaten, chromium-6 and medical implants
New Approach Methodologies (NAMs) are test methods that reduce the use of laboratory animals. These can be used for the safety assessment of chemical substances. Realising NAMs in legislation and regulations is a complex process in which many parties are involved. RIVM has mapped out this process with the Landscape NAMs.
The development of NAMs of...
Between 1984 and 2006, Ministry of Defence personnel maintained American equipment at the so-called POMS sites (POMS stands for Prepositioned Organizational Materiel Storage) in the Netherlands. They worked with several materials, including Chemical Agent Resistant Coating (CARC), a protective top coating for army vehicles.
It is possible that wor...
Between 1984 and 2006, Ministry of Defence personnel maintained American equipment at the so-called POMS sites (POMS stands for Prepositioned Organizational Materiel Storage) located in the Netherlands. They may have been exposed at the workplace to chromium-6 which was primarily contained in the primer used to paint the equipment. The risk of deve...
Oxygen (O2) levels in the mammalian embryo range between 2.4% and 8%. The cardiac embryonic stem cell test (ESTc) is a model for developmental toxicity predictions, which is usually performed under atmospheric O2 levels of 20%. We investigated the chemical sensitivity of the ESTc carried out under 20% O2, using embryonic stem cells (ESC) cultured u...
Animal-free assessment of compound-induced developmental neurotoxicity will most likely be based on batteries of multiple in vitro tests. The optimal battery is built by combining tests with complementary biological domains that together ideally cover all relevant toxicity pathways. Thus, biological domain definition, i.e. which biological processe...
Human induced pluripotent stem cells (iPSCs) can capture the diversity in the general human population as well as provide deeper insight in cellular mechanisms. This makes them suitable to study both fundamental and applied research subjects, such as disease modeling, gene-environment interactions, personalized medicine, and chemical toxicity. In a...
In vitro tests are increasingly applied in chemical hazard assessment. Basic culture conditions may affect the outcome of in vitro tests and should be optimised to reduce false predictions. The neural embryonic stem cell test (ESTn) can predict early neurodevelopmental effects of chemicals, as it mimics the differentiation of stem cells towards the...
Human embryonic stem cell neuronal differentiation models provide promising in vitro tools for the prediction of developmental neurotoxicity of chemicals. Such models mimic essential elements of human relevant neuronal development, including the differentiation of a variety of brain cell types and their neuronal network formation as evidenced by sp...
The importance of oxygen tension in in vitro cultures and its effect on embryonic stem cell (ESC) differentiation has been widely acknowledged. Research has mainly focussed on ESC maintenance or on one line of differentiation and only few studies have examined the potential relation between oxygen tension during ESC maintenance and differentiation....
There is a need for in vitro tests for the evaluation of chemicals and pharmaceuticals that may cause developmental neurotoxicity (DNT) in humans. The neural embryonic stem cell test (ESTn) is such an in vitro test that mimics early neural differentiation. The aim of this study was to define the biological domain of ESTn based on the expression of...
In vitro assays to assess developmental neurotoxicity of chemicals are highly desirable. The murine neural embryonic stem cell test (ESTn) can mimic parts of early differentiation of embryonic brain and may therefore be useful for this purpose. The aim of this study was to investigate whether this test is able to rank the toxic potencies of three v...
Non-animal testing methods, in vitro and in silico, are indispensable for improving human risk assessment of chemicals and reducing the number of laboratory animals used. Such an approach requires a series of complementary in vitro and in silico methods to study effects of chemicals on complex processes, such as embryonic development. The murine ne...
