title: iPS cell derived neuronal cells for drug discovery.
abstract: Owing to the inherent disconnect between drug pharmacology in heterologous cellular models and drug efficacy in vivo, the quest for more predictive in vitro systems is one of the most urgent challenges of modern drug discovery. An improved pharmacological in vitro profiling would employ primary samples of the proper drug-targeted human tissue or the bona fide human disease-relevant cells. With the advent of induced pluripotent stem (iPS) cell technology the facilitated access to a variety of disease-relevant target cells is now held out in prospect. In this review, we focus on the use of human iPS cell derived neurons for high throughput pharmaceutical drug screening, employing detection technologies that are sufficiently sensitive to measure signaling in cells with physiological target protein expression levels.
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co KG, Department of Lead Identification and Optimization Support, Birkendorfer Strasse 65, 88397 Biberach, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Heilker
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co KG, Department of Lead Identification and Optimization Support, Birkendorfer Strasse 65, 88397 Biberach, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Traub
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Reinhardt
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, Germany; University of Münster, Medical Faculty, Domagkstrasse 3, 48149 Münster, Germany.
authors.forename: Hans R
authors.initials: HR
authors.lastname: Schöler
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, Germany. Electronic address: jsternec@mpi-muenster.mpg.de.
authors.forename: Jared
authors.initials: J
authors.lastname: Sterneckert
mesh_terms: D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects*
keywords: disease modeling; drug discovery; expandable neural progenitors; high content screening; high throughput RT-PCR; induced pluripotent stem (iPS) cells; phenotypic screening