Cardiomyocytes from human pluripotent stem cells: from laboratory curiosity to industrial biomedical platform

Denning, Chris and Borgdorff, Viola and Crutchley, James and Firth, Karl S.A. and George, Vinoj and Kalra, Spandan and Kondrashov, Alexander and Hoang, Minh Duc and Mosqueira, Diogo and Patel, Asha and Prodanov, Ljupcho and Rajamohan, Divya and Skarnes, William C. and Smith, James G.W. and Young, Lorraine E. (2016) Cardiomyocytes from human pluripotent stem cells: from laboratory curiosity to industrial biomedical platform. BBA - Biochimica et Biophysica Acta, 1863 (7). pp. 1728-1748. ISSN 0006-3002

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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
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
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine
Identification Number: 10.1016/j.bbamcr.2015.10.014
Depositing User: Blay, James
Date Deposited: 25 Oct 2016 07:37
Last Modified: 13 Oct 2017 18:09
URI: http://eprints.nottingham.ac.uk/id/eprint/37771

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