• Chris Denning, Viola Borgdorff, James Crutchley, Karl S A Firth, Vinoj George, Spandan Kalra, Alexander Kondrashov, Minh Duc Hoang, Diogo Mosqueira, Asha Patel, Ljupcho Prodanov, Divya Rajamohan, William C Skarnes, James G W Smith, and Lorraine E Young.
• Department of Stem Cell Biology, Centre for Biomolecular Sciences, University of Nottingham, NG7 2RD, United Kingdom. Electronic address: chris.denning@nottingham.ac.uk.
• Biochim. Biophys. Acta. 2016 Jul 1; 1863 (7 Pt B): 1728-48.

AbstractCardiomyocytes from human pluripotent stem cells (hPSCs-CMs) could revolutionise biomedicine. Global burden of heart failure will soon reach USD $90bn, while unexpected cardiotoxicity underlies 28% of drug withdrawals. Advances in hPSC isolation, Cas9/CRISPR genome engineering and hPSC-CM differentiation have improved patient care, progressed drugs to clinic and opened a new era in safety pharmacology. Nevertheless, predictive cardiotoxicity using hPSC-CMs contrasts from failure to almost total success. Since this likely relates to cell immaturity, efforts are underway to use biochemical and biophysical cues to improve many of the ~30 structural and functional properties of hPSC-CMs towards those seen in adult CMs. Other developments needed for widespread hPSC-CM utility include subtype specification, cost reduction of large scale differentiation and elimination of the phenotyping bottleneck. This review will consider these factors in the evolution of hPSC-CM technologies, as well as their integration into high content industrial platforms that assess structure, mitochondrial function, electrophysiology, calcium transients and contractility. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

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