CHRIS DENNING chris.denning@nottingham.ac.uk
Professor of Stem Cell Biology
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.
Authors
Viola Borgdorff
James Crutchley
Karl S.A. Firth
Vinoj George
Spandan Kalra
ALEXANDER KONDRASHOV a.kondrashov@nottingham.ac.uk
Research Fellow
Minh Duc Hoang
Diogo Mosqueira
Asha Patel
Ljupcho Prodanov
Divya Rajamohan
William C. Skarnes
James G.W. Smith
Lorraine E. Young
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.
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 |
DOI | https://doi.org/10.1016/j.bbamcr.2015.10.014 |
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 |
Public URL | https://nottingham-repository.worktribe.com/output/798234 |
Publisher URL | http://www.sciencedirect.com/science/article/pii/S0167488915003675 |
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0
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