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Current status of human pluripotent stem cell based in vitro toxicity tests

Martina Klaric1,Johannes Winkler2,Kinga Vojnits1,Kesavan Meganathan2,Smita Jagtap2,Roberto Ensenat-Waser1,Juergen Hescheler2,Agapios Sachinidis2,Susanne Bremer-Hoffmann1,*
1
Systems toxicology unit, ECVAM, European Centre for the Validation of Alternative Methods, T.P. 580, IHCP, JRC, European Commission, via E. Fermi 2749, 21027 Ispra,VA, Italy
2
Institute of Neurophysiology, University of Cologne, Robert-Koch- Strasse 39, D-50931 Cologne, Germany
DOI: 10.2741/S361 Volume 5 Issue 1, pp.118-133
Published: 01 January 2013
*Corresponding Author(s):  
Susanne Bremer-Hoffmann
E-mail:  
susanne.bremer-hoffmann@ec.europa.eu
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.

Key words

Human pluripotent stem cells, In vitro toxicity testing, Test development criteria, Review

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Martina Klaric, Johannes Winkler, Kinga Vojnits, Kesavan Meganathan, Smita Jagtap, Roberto Ensenat-Waser, Juergen Hescheler, Agapios Sachinidis, Susanne Bremer-Hoffmann. Current status of human pluripotent stem cell based in vitro toxicity tests. Frontiers in Bioscience-Scholar. 2013. 5(1); 118-133.