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Human pluripotent stem cells as tools for high-throughput and high-content screening in drug discovery

Authors Allison TF, Powles-Glover NS, Biga V, Andrews PW, Barbaric I

Received 15 November 2014

Accepted for publication 21 January 2015

Published 11 March 2015 Volume 2015:5 Pages 1—13

DOI https://doi.org/10.2147/IJHTS.S58113

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Editor who approved publication: Dr Wayne Wahls

Thomas F Allison,1 Nicola S Powles-Glover,2 Veronica Biga,3 Peter W Andrews,1 Ivana Barbaric1

1Centre for Stem Cell Biology, Department of Biomedical Science, University of Sheffield, Sheffield, 2AstraZeneca, Alderley Edge, 3Centre for Signal Processing and Complex Systems, Department of Automatic Control and Systems Engineering, University of Sheffield, Sheffield, UK

Abstract: A significant bottleneck in drug discovery is the lack of suitable models for sensitive, reliable, and rapid assessment of lead molecules in preclinical stages of drug discovery. Human pluripotent stem cells (hPSCs) derived either from early human blastocysts (human embryonic stem cells) or by reprogramming somatic cells to a pluripotent state (human-induced pluripotent stem cells) can be propagated extensively in vitro while retaining the ability to differentiate into any specialized cell type within the body. In this review, we discuss how these unique features of hPSCs could offer a way of producing relevant in vitro models amenable to high-throughput testing for drug discovery. We summarize recent progress in inducing differentiation of hPSCs to specific cell types, and describe the ongoing efforts in applying hPSCs and their differentiated derivatives in disease modeling, drug discovery, and developmental toxicology. Moreover, we review the applications of high-content imaging assays in detecting the changes in the phenotype of hPSCs and their differentiated progeny. Finally, we highlight challenges that need to be overcome in order for the application of hPSC technology to fully benefit drug discovery.

Keywords: human pluripotent stem cells, drug discovery, high-content assays

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