We are developing a model based on human embryonic stem cells...
and the model mimics a part of the brain development.
The model is used to test the safety of compounds.
VO: Disruption of brain development may have enormous impact on future life...
and might result in disorders such as ADHD or mental retardation.
It is known that genetic factors contribute to these disorders...
but environmental factors, such as exposure to compounds...
may also play a role.
The effect of compounds on...
the developing brain is largely unknown.
Therefore, there is a high need...
for testing adverse effects on the brain development of compound exposure.
VO: A testing strategy with in vitro and in silico methods...
based on the biology of human brain development...
will help to unravel the adverse effects of compounds on the developing brain.
HESSEL: RIVM is developing an in vitro method...
that mimics parts of the brain development.
This model is based on human stem cells.
Human embryonic stem cells...
and induced pluripotent stem cells from blood can be used.
As a first step, these stem cells are differentiated into neural progenitor cells.
These neural progenitor cells can be frozen...
or re-cultured and differentiated in a neuron-astrocyte network, within 10 days.
This is a relatively short and robust protocol.
VO: With this differentiation method...
the model can develop a functional neuronal network.
HESSEL: Characterisation of the model with gene and protein expression...
show that we have neurons and astrocytes within the model...
and the ratio of these cells differ during the 10-day differentiation period.
After 3 days, we even have spontaneous electrical activity within the model.
With this model we show that compounds...
affect neuronal differentiation and this is in line with in vivo data.
This model can be an important component in a testing strategy...
for developmental neurotoxicity...
and to measure the effect of chemicals and pharmaceuticals on the developing brain.
This method is human-relevant and animal-free...
and is based on mechanistic knowledge of human biology of brain development.