Neurotoxicity of active compounds--establishment of hESC-lines and proteomics technologies for human embryo- and neurotoxicity screening and biomarker identification.
Pharmaceutical and chemical industries are facing new challenges for hazard and risk assessment from regulatory agencies. Especially for potential embryotoxicity of active compounds, conclusions from animal testing remain problematic due to numerous species-specific effects. Developmental toxicity screening preferentially should be performed with human material. Appropriate models are scarce or missing, and the development of a human in vitro model for the molecular characterisation of embryotoxic effects appears to be highly desirable. The outstanding advantages of a human embryonic stem cell (hESC) based in vitro screening model for embryonic neurotoxicity become clear from corresponding results from a murine ESC-screening system. This in vitro test system is based on neuronal differentiated murine embryonic stem cells and quantitative differential proteomic display techniques to identify biomarkers for neurotoxicity. Results are superior to those of conventional array technologies (nucleic acids), because the proteomic analysis covers posttranslational modifications. Under the new strict guidelines for stem cell importation of the German Ministry of Health and a Central Ethics Commission for Stem Cell Research, it is now possible for the first time to exploit the outstanding features of human embryonic stem cells to establish an innovative screening method for embryo- and neurotoxicity and to identify toxicity biomarkers without using animal-based in vitro or in vivo systems.
Klemm
Martina
M
ProteoSys AG, D-Mainz, Germany. martina.klemm@proteosys.com
Schrattenholz
André
A
D000826:Animal Testing Alternatives; D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D015507:Drugs, Investigational / Q000633:toxicity*; D004622:Embryo, Mammalian / Q000166:cytology* / Q000187:drug effects; D004992:Ethics, Medical; D005858:Germany; D006801:Humans; D051379:Mice; D009420:Nervous System / Q000187:drug effects* / Q000196:embryology; D040901:Proteomics / Q000379:methods*; D015398:Signal Transduction; D013045:Species Specificity; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D018675:Toxicity Tests
D015415:Biomarkers; D015507:Drugs, Investigational