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Review
. 2014 Feb 21;289(8):4555-61.
doi: 10.1074/jbc.R113.481028. Epub 2013 Dec 20.

Stem cells and stem cell-derived tissues and their use in safety assessment

Kyle Kolaja  1
Affiliations
Review

Stem cells and stem cell-derived tissues and their use in safety assessment

Kyle Kolaja. J Biol Chem. .

Abstract

Toxicology has long relied on animal models in a tedious approach to understanding risk of exposure to an uncharacterized molecule. Stem cell-derived tissues can be made in high purity, quality, and quantity to enable a new approach to this problem. Currently, stem cell-derived tissues are primarily "generic" genetic backgrounds; the future will see the integration of various genetic backgrounds and complex three-dimensional models to create truly unique in vitro organoids. This minireview focuses on the state of the art of a number of stem cell-derived tissues and details their application in toxicology.

Keywords: Cardiovascular; Drug Development; Drug Discovery; Embryonic Stem Cell; Hepatocyte; Induced Pluripotent Stem Cells; Neurons; Stem Cells; Toxicology.

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Figures

FIGURE 1.
FIGURE 1.
Potential of iPSC-derived tissues in safety assessment. Drug-induced injury models have been developed in a number of target organs. Examples from neurons, hepatocytes, and cardiomyocytes have demonstrated physiologically relevant disease phenotypes as well as drug-induced toxicities. In hPSC-derived neurons, amyloid-β accumulation and neurotoxic drugs will induce neurite atrophy prior to neuronal cell death. In hPSC-derived hepatocytes, the steatosis-inducing drug amiodarone recapitulates this finding in vitro. Finally, hPSC-derived cardiomyocytes accurately reproduce and can be used to predict drug-induced arrhythmias. RLU, relative light units; EADs, early afterdepolarizations.
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