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Trends Mol Med. 2019 Jun;25(6):470-481. doi: 10.1016/j.molmed.2019.04.003. Epub 2019 May 23.

Road Map for Development of Stem Cell-Based Alternative Test Methods.

Author information

1
Institute of Neurophysiology and Centre for Molecular Medicine Cologne (CMMC), University of Cologne (UKK), Cologne, Germany. Electronic address: a.sachinidis@uni-koeln.de.
2
Leibniz Research Centre for Working Environment and Human Factors, Technical University of Dortmund (IfADo), 44139 Dortmund, Germany.
3
Institute of Neurophysiology and Centre for Molecular Medicine Cologne (CMMC), University of Cologne (UKK), Cologne, Germany.
4
SWS, Wingertstrasse 25, 64390 Erzhausen, Germany.
5
Leibniz Research Centre for Working Environment and Human Factors, Technical University of Dortmund (IfADo), 44139 Dortmund, Germany. Electronic address: Hengstler@ifado.de.

Abstract

Much progress has been made in establishing strategies for differentiation of induced human pluripotent stem cells (hiPSCs). However, differentiated hiPSCs are not yet routinely used for prediction of toxicity. Here, limiting factors are summarised and possibilities for improvement are discussed, with a focus on hepatocytes, cardiomyocytes, tubular epithelial cells, and developmental toxicity. Moreover, we make recommendations for further fine-tuning of differentiation protocols for hiPSCs to hepatocyte-like cells by comparing individual steps of currently available protocols to the mechanisms occurring during embryonic development. A road map is proposed to facilitate test system development, including a description of the most useful performance metrics.

KEYWORDS:

alternative testing strategies; cardiotoxicity; developmental toxicity; drug discovery; hepatotoxicity; nephrotoxicity; neurotoxicity; pluripotent stem cells

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