title: Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation.
abstract: 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.
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Neurophysiology, University of Cologne.
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Shinde
authors.affiliation: Department of Biology, University of Konstanz.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Klima
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Neurophysiology, University of Cologne.
authors.forename: Perumal Srinivasan
authors.initials: PS
authors.lastname: Sureshkumar
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Neurophysiology, University of Cologne.
authors.forename: Kesavan
authors.initials: K
authors.lastname: Meganathan
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Neurophysiology, University of Cologne.
authors.forename: Smita
authors.initials: S
authors.lastname: Jagtap
authors.affiliation: Department of Statistics, Technical University of Dortmund.
authors.forename: Eugen
authors.initials: E
authors.lastname: Rempel
authors.affiliation: Department of Statistics, Technical University of Dortmund.
authors.forename: Jörg
authors.initials: J
authors.lastname: Rahnenführer
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors, Technical University of Dortmund.
authors.forename: Jan Georg
authors.initials: JG
authors.lastname: Hengstler
authors.affiliation: Department of Biology, University of Konstanz.
authors.forename: Tanja
authors.initials: T
authors.lastname: Waldmann
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Neurophysiology, University of Cologne.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hescheler
authors.affiliation: Department of Biology, University of Konstanz.
authors.forename: Marcel
authors.initials: M
authors.lastname: Leist
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Neurophysiology, University of Cologne; a.sachinidis@uni-koeln.de.
authors.forename: Agapios
authors.initials: A
authors.lastname: Sachinidis
mesh_terms: D000826:Animal Testing Alternatives / Q000379:methods; D006801:Humans; D039904:Pluripotent Stem Cells / Q000187:drug effects*; D049490:Systems Biology / Q000379:methods*; D018675:Toxicity Tests / Q000379:methods*