Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation

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2015
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Shinde, Vaibhav
Sureshkumar, Perumal Srinivasan
Meganathan, Kesavan
Jagtap, Smita
Rempel, Eugen
Rahnenführer, Jörg
Hengstler, Jan Georg
Hescheler, Jürgen
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Journal of Visualized Experiments (JoVE). 2015(100), e52333. eISSN 1940-087X. Available under: doi: 10.3791/52333
Zusammenfassung

Efficient protocols to differentiate human pluripotent stem cells to various tissues in combination with -omics technologies opened up new horizons for in vitro toxicity testing of potential drugs. To provide a solid scientific basis for such assays, it will be important to gain quantitative information on the time course of development and on the underlying regulatory mechanisms by systems biology approaches. Two assays have therefore been tuned here for these requirements. In the UKK test system, human embryonic stem cells (hESC) (or other pluripotent cells) are left to spontaneously differentiate for 14 days in embryoid bodies, to allow generation of cells of all three germ layers. This system recapitulates key steps of early human embryonic development, and it can predict human-specific early embryonic toxicity/teratogenicity, if cells are exposed to chemicals during differentiation. The UKN1 test system is based on hESC differentiating to a population of neuroectodermal progenitor (NEP) cells for 6 days. This system recapitulates early neural development and predicts early developmental neurotoxicity and epigenetic changes triggered by chemicals. Both systems, in combination with transcriptome microarray studies, are suitable for identifying toxicity biomarkers. Moreover, they may be used in combination to generate input data for systems biology analysis. These test systems have advantages over the traditional toxicological studies requiring large amounts of animals. The test systems may contribute to a reduction of the costs for drug development and chemical safety evaluation. Their combination sheds light especially on compounds that may influence neurodevelopment specifically.

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570 Biowissenschaften, Biologie
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Developmental Biology, Issue 100, Human embryonic stem cells, developmental toxicity, neurotoxicity, neuroectodermal progenitor cells, immunoprecipitation, differentiation, cytotoxicity, embryopathy, embryoid body
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ISO 690SHINDE, Vaibhav, Stefanie KLIMA, Perumal Srinivasan SURESHKUMAR, Kesavan MEGANATHAN, Smita JAGTAP, Eugen REMPEL, Jörg RAHNENFÜHRER, Jan Georg HENGSTLER, Tanja WALDMANN, Jürgen HESCHELER, Marcel LEIST, Agapios SACHINIDIS, 2015. Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation. In: Journal of Visualized Experiments (JoVE). 2015(100), e52333. eISSN 1940-087X. Available under: doi: 10.3791/52333
BibTex
@article{Shinde2015-06-17Human-32156,
  year={2015},
  doi={10.3791/52333},
  title={Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation},
  number={100},
  journal={Journal of Visualized Experiments (JoVE)},
  author={Shinde, Vaibhav and Klima, Stefanie and Sureshkumar, Perumal Srinivasan and Meganathan, Kesavan and Jagtap, Smita and Rempel, Eugen and Rahnenführer, Jörg and Hengstler, Jan Georg and Waldmann, Tanja and Hescheler, Jürgen and Leist, Marcel and Sachinidis, Agapios},
  note={Article Number: e52333}
}
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