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Denning, C, Borgdorff, V, Crutchley, J, Firth, K, George, V, Kalra, S, Kondrashov, A, Hoang, MD, Mosqueira, D, Patel, A, Prodanov, L, Rajamohan, D, Skarnes, W, Smith, J and Young, L (2015) Cardiomyocytes from human pluripotent stem cells: From laboratory curiosity to industrial biomedical platform. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1863 (7). 1728 - 1748.

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Abstract

Cardiomyocytes 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.

Item Type: Article
Uncontrolled Keywords: Human embryonic stem cells; Human induced pluripotent stem cells; Cas9/CRISPR genome editing; Cardiomyocytes; Drug screening; Disease modelling; Maturation factors; Muscular thin films; Engineered heart tissue; Automated scalability; High content platforms; Calcium imaging; Electrophysiology; Mitochondria; Contractility
Subjects: R Medicine > R Medicine (General)
R Medicine > RA Public aspects of medicine
Divisions: Faculty of Medicine and Health Sciences > Primary Care Health Sciences
Depositing User: Symplectic
Date Deposited: 14 Jun 2018 10:02
Last Modified: 23 Apr 2019 10:30
URI: https://eprints.keele.ac.uk/id/eprint/5020

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