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发帖数: 2275 | 1 请发到：h******[email protected]
先谢过了！
Curr Med Chem. 2012 Dec 1;19(35):6065-71.
Characterisation of a Neural Teratogenicity Assay Based on Human ESCs
Differentiation Following Exposure to Valproic Acid.
Colleoni S, Galli C, Gaspar JA, Meganathan K, Jagtap S, Hescheler J,
Sachinidis A, Lazzari G.
SourceAvantea, Via Porcellasco 7/f, 26100 Cremona, Italy. silviacolleoni@
avantea.it.
Abstract
The development of in vitro testing strategies for chemical and drug
screening is a priority need in order to protect human health, to increase
safety, to reduce the number of animals required for conventional testing
methods and finally to meet the deadlines of current legislations. The aim
of this work was to design an alternative testing method based on human
embryonic stem cells for the detection of prenatal neural toxicity. For this
purpose we have created a model based on the generation of neural rosettes,
reproducing in vitro the gastrulation events recapitulating the formation
of the neural tube in vivo. To validate the model we have exposed this
complex cell system to increasing concentrations of valproic acid, a known
teratogenic agent, to analyse the morphological and molecular changes
induced by the toxicant. Specific assays were applied to discriminate
between cytotoxicity and specific neural toxicity. Transcriptomic analysis
was performed with a microarray Affimetrix platform and validated by
quantitative real time RT-PCR for the expression of genes involved in early
neural development, neural tube formation and neural cells migration, key
biological processes in which the effect of valproic acid is most relevant.
The results demonstrated that neural rosette cells respond to valproic acid
exposure with molecular and morphological changes similar to those observed
in vivo, indicating that this method represents a promising alternative test
for the detection of human prenatal neural toxicity. | c****z
发帖数: 299 | | x********e
发帖数: 2275 | 3 多谢！
【在 c****z 的大作中提到】
: done~
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