WEBVTT 

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We want to make human-relevant...
-...animal-free models...

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for neurodevelopmental health.

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♪ UPTEMPO BEAT ♪

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ELLEN HESSEL: The prevalence
of neurodevelopmental disorders...

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is increasing worldwide,
including cognitive impairments.

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There's evidence that exposure
to chemicals may contribute...

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to this increased prevalence
of neurodevelopmental disorders.

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But there is
very little causal evidence for this.

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This is because human brain
development is extremely complex.

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And the models that are used to test
this link, which are mostly animal studies...

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do not translate very well to humans.

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That's why we need to research
the effect of chemicals...

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in more human relevant models.

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♪ UPTEMPO MUSIC ♪

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VICTORIA DE LEEUW: We're going
to use induced pluripotent stem cells...

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that we will differentiate
into neuronal cells.

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Upon differentiation these cells will make
connections with each other...

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which is a crucial cell process for normal
brain development and cognition.

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We're not going to use
any type of stem cell...

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but cells of which we know the history
and genetic makeup.

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These cells will be derived from
blood samples of healthy participants...

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of the Doetinchem cohort
after they've given informed consent.

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VICTORIA: We will also induce
gene mutations in these cells...

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of which we know that they are important
for normal cognition...

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using CRISPR-Cas technology.

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We will select these genes together
with clinicians from the Amsterdam UMC.

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We will expose these cells to chemicals
while they are differentiating into brain cells.

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The assumption is that when
the differentiation of these cells...

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is affected,
that the chemical is potentially toxic.

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And moreover, it allows us to look
at the underlying mechanisms.

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MARTIJN DOLLÉ:
First we have to make the stem cells.

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Blood cells from consenting Doetinchem
cohort participants will be reprogramed...

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by the specialized iPS facility
at the Erasmus Medical Center.

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This will lead to a stem cell resource
that will be kept at the RIVM.

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We will differentiate
these stem cells to functional neurons...

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and expose them to harmful compounds
at the same time.

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MARTIJN: By exposing these
differentiating cells from different people...

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with and without disabled genes
for normal cognitive function...

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we intend to gain insights on how genetic
backgrounds and specific mutations...

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affect the susceptibility
of brain cells to chemical compounds.

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MARTIJN: If our approach
is successful for the brain...

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the stem cell resource
created in this project can be used...

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to generate other tissues
and study the effect of exposures...

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 in combination with genetic variation
on human health...

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using human-relevant
and animal-free models.

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♪ UPTEMPO BEAT ♪