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

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

doi:10.1016/j.bbamcr.2015.10.014

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

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

Research output: Contribution to journal › Article › peer-review

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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 26 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.

Original language	English
Pages (from-to)	1728-1748
Number of pages	21
Journal	Biochimica et Biophysica Acta
Volume	1863
Issue number	7
Early online date	31 Oct 2015
DOIs	https://doi.org/10.1016/j.bbamcr.2015.10.014
Publication status	Published - Jul 2016

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.bbamcr.2015.10.014Licence: CC BY-NC-ND

BBA-Molecular Cell ResearchAccepted author manuscript, 1.63 MBLicence: CC BY-NC-ND

http://eprints.nottingham.ac.uk/37771/Licence: CC BY-NC-ND

Cite this

Denning, C., Borgdorff, V., Crutchley, J., Firth, K. S. A., George, V., Kalra, S., Kondrashov, A., Hoang, M. D., Mosqueira, D., Patel, A., Prodanov, L., Rajamohan, D., Skarnes, W. C., Smith, J. G. W., & Young, L. E. (2016). Cardiomyocytes from human pluripotent stem cells: from laboratory curiosity to industrial biomedical platform. Biochimica et Biophysica Acta, 1863(7), 1728-1748. https://doi.org/10.1016/j.bbamcr.2015.10.014

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title = "Cardiomyocytes from human pluripotent stem cells: from laboratory curiosity to industrial biomedical platform",

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 26 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.",

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",

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

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Denning, C, Borgdorff, V, Crutchley, J, Firth, KSA, George, V, Kalra, S, Kondrashov, A, Hoang, MD, Mosqueira, D, Patel, A, Prodanov, L, Rajamohan, D, Skarnes, WC, Smith, JGW & Young, LE 2016, 'Cardiomyocytes from human pluripotent stem cells: from laboratory curiosity to industrial biomedical platform', Biochimica et Biophysica Acta, vol. 1863, no. 7, pp. 1728-1748. https://doi.org/10.1016/j.bbamcr.2015.10.014

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KW - muscular thin films

KW - engineered heart tissue

KW - automated scalability

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KW - calcium imaging

KW - electrophysiology

KW - mitochondria

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