WEBVTT 

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We are developing a model based on 
human embryonic stem cells...

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and the model mimics a part
of the brain development.

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The model is used to test 
the safety of compounds.

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VO: Disruption of brain development 
may have enormous impact on future life...

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and might result in disorders such as
ADHD or mental retardation.

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It is known that genetic factors 
contribute to these disorders...

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but environmental factors, such as 
exposure to compounds...

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may also play a role.

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The effect of compounds on...

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 the developing brain is largely unknown.

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Therefore, there is a high need...

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for testing adverse effects on the brain 
development of compound exposure. 

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VO: A testing strategy with 
in vitro and in silico methods...

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based on the biology of 
human brain development...

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will help to unravel the adverse effects 
of compounds on the developing brain.

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HESSEL: RIVM is developing 
an in vitro method...

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that mimics parts of the brain development.

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This model is based on human stem cells.

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Human embryonic stem cells...

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and induced pluripotent stem cells 
from blood can be used.

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As a first step, these stem cells are 
differentiated into neural progenitor cells.

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These neural progenitor cells 
can be frozen...

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or re-cultured and differentiated in a 
neuron-astrocyte network, within 10 days.

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This is a relatively short 
and robust protocol.

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VO: With this differentiation method...

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the model can develop a 
functional neuronal network.

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HESSEL: Characterisation of the model 
with gene and protein expression...

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show that we have neurons and 
astrocytes within the model...

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and the ratio of these cells differ 
during the 10-day differentiation period.

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After 3 days, we even have spontaneous 
electrical activity within the model.

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With this model we show that compounds...

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affect neuronal differentiation and
this is in line with in vivo data.

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This model can be an important component 
in a testing strategy...

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for developmental neurotoxicity...

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and to measure the effect of chemicals and 
pharmaceuticals on the developing brain.

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This method is human-relevant 
and animal-free...

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and is based on mechanistic knowledge of 
human biology of brain development.