title: Current status of human pluripotent stem cell based in vitro toxicity tests.
abstract: The present review assesses the current status of in vitro tests based on human pluripotent stem cell-derived toxicologically relevant target cells. The majority of the evaluated test systems are in the phase of test development. In particular the success rates of differentiation protocols and their reproducibility are varying depending on different culture conditions but also on the assessed marker panel and the functional evaluation of the cells. However, the amount of differentiated cells decreases in relation to their maturation status. No harmonization has been achieved yet about the required maturation status of the cellular models to be used for toxicological applications. Even with an established cellular model, the selection of appropriate readouts is challenging. Some areas of toxicity, such as developmental toxicity, suffer from insufficient knowledge on predictive biomarkers which leads to difficulties in the selection of the most appropriate endpoints. In this heterogeneous context the rapidly increasing knowledge about 'omics' technologies, might lead to an improvement of the current situation and allow the establishment of more predictive human in vitro toxicity tests.
authors.affiliation: Systems toxicology unit, ECVAM, European Centre for the Validation of Alternative Methods, IHCP, JRC, European Commission, Ispra, VA, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Klaric
authors.forename: Johannes
authors.initials: J
authors.lastname: Winkler
authors.forename: Kinga
authors.initials: K
authors.lastname: Vojnits
authors.forename: Kesavan
authors.initials: K
authors.lastname: Meganathan
authors.forename: Smita
authors.initials: S
authors.lastname: Jagtap
authors.forename: Roberto
authors.initials: R
authors.lastname: Ensenat-Waser
authors.forename: Juergen
authors.initials: J
authors.lastname: Hescheler
authors.forename: Agapios
authors.initials: A
authors.lastname: Sachinidis
authors.forename: Susanne
authors.initials: S
authors.lastname: Bremer-Hoffmann
mesh_terms: D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D039904:Pluripotent Stem Cells / Q000187:drug effects*; D018675:Toxicity Tests / Q000379:methods*