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

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 differenti...

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Main Authors: 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.
Format: Article
Published: Elsevier 2016
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Online Access:https://eprints.nottingham.ac.uk/37771/
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author 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.
author_facet 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.
author_sort Denning, Chris
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-377712020-05-04T17:58:50Z https://eprints.nottingham.ac.uk/37771/ 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. 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. Elsevier 2016-07-31 Article PeerReviewed 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. 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 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 http://www.sciencedirect.com/science/article/pii/S0167488915003675 doi:10.1016/j.bbamcr.2015.10.014 doi:10.1016/j.bbamcr.2015.10.014
spellingShingle 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
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.
Cardiomyocytes from human pluripotent stem cells: from laboratory curiosity to industrial biomedical platform
title Cardiomyocytes from human pluripotent stem cells: from laboratory curiosity to industrial biomedical platform
title_full Cardiomyocytes from human pluripotent stem cells: from laboratory curiosity to industrial biomedical platform
title_fullStr Cardiomyocytes from human pluripotent stem cells: from laboratory curiosity to industrial biomedical platform
title_full_unstemmed Cardiomyocytes from human pluripotent stem cells: from laboratory curiosity to industrial biomedical platform
title_short Cardiomyocytes from human pluripotent stem cells: from laboratory curiosity to industrial biomedical platform
title_sort cardiomyocytes from human pluripotent stem cells: from laboratory curiosity to industrial biomedical platform
topic 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
url https://eprints.nottingham.ac.uk/37771/
https://eprints.nottingham.ac.uk/37771/
https://eprints.nottingham.ac.uk/37771/