We want to make human-relevant... -...animal-free models...
for neurodevelopmental health.
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ELLEN HESSEL: The prevalence of neurodevelopmental disorders...
is increasing worldwide, including cognitive impairments.
There's evidence that exposure to chemicals may contribute...
to this increased prevalence of neurodevelopmental disorders.
But there is very little causal evidence for this.
This is because human brain development is extremely complex.
And the models that are used to test this link, which are mostly animal studies...
do not translate very well to humans.
That's why we need to research the effect of chemicals...
in more human relevant models.
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VICTORIA DE LEEUW: We're going to use induced pluripotent stem cells...
that we will differentiate into neuronal cells.
Upon differentiation these cells will make connections with each other...
which is a crucial cell process for normal brain development and cognition.
We're not going to use any type of stem cell...
but cells of which we know the history and genetic makeup.
These cells will be derived from blood samples of healthy participants...
of the Doetinchem cohort after they've given informed consent.
VICTORIA: We will also induce gene mutations in these cells...
of which we know that they are important for normal cognition...
using CRISPR-Cas technology.
We will select these genes together with clinicians from the Amsterdam UMC.
We will expose these cells to chemicals while they are differentiating into brain cells.
The assumption is that when the differentiation of these cells...
is affected, that the chemical is potentially toxic.
And moreover, it allows us to look at the underlying mechanisms.
MARTIJN DOLLÉ: First we have to make the stem cells.
Blood cells from consenting Doetinchem cohort participants will be reprogramed...
by the specialized iPS facility at the Erasmus Medical Center.
This will lead to a stem cell resource that will be kept at the RIVM.
We will differentiate these stem cells to functional neurons...
and expose them to harmful compounds at the same time.
MARTIJN: By exposing these differentiating cells from different people...
with and without disabled genes for normal cognitive function...
we intend to gain insights on how genetic backgrounds and specific mutations...
affect the susceptibility of brain cells to chemical compounds.
MARTIJN: If our approach is successful for the brain...
the stem cell resource created in this project can be used...
to generate other tissues and study the effect of exposures...
in combination with genetic variation on human health...
using human-relevant and animal-free models.
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