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

Denning, Chris; Borgdorff, Viola; Crutchley, James; Firth, Karl S.A.; George, Vinoj; Kalra, Spandan; Kondrashov, Alexander; Hoang, Minh Duc; Mosqueira, Diogo; Patel, Asha; Prodanov, Ljupcho; Rajamohan, Divya; Skarnes, William C.; Smith, James G.W.; Young, Lorraine E.

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Professor of Stem Cell Biology

Viola Borgdorff

James Crutchley

Karl S.A. Firth

Vinoj George

Spandan Kalra

Minh Duc Hoang

Diogo Mosqueira

Asha Patel

Ljupcho Prodanov

Divya Rajamohan

William C. Skarnes

James G.W. Smith

Lorraine E. Young


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.

Journal Article Type Article
Acceptance Date Oct 20, 2015
Online Publication Date Oct 31, 2015
Publication Date Jul 31, 2016
Deposit Date Oct 25, 2016
Publicly Available Date Oct 25, 2016
Journal BBA - Biochimica et Biophysica Acta
Print ISSN 0006-3002
Electronic ISSN 0006-3002
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 1863
Issue 7
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 platform
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