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

Authors
  • Denning, Chris1
  • Borgdorff, Viola2
  • Crutchley, James2
  • Firth, Karl S A2
  • George, Vinoj2
  • Kalra, Spandan2
  • Kondrashov, Alexander2
  • Hoang, Minh Duc2
  • Mosqueira, Diogo2
  • Patel, Asha2
  • Prodanov, Ljupcho2
  • Rajamohan, Divya2
  • Skarnes, William C3
  • Smith, James G W2
  • Young, Lorraine E2
  • 1 Department of Stem Cell Biology, Centre for Biomolecular Sciences, University of Nottingham, NG7 2RD, United Kingdom. Electronic address: [email protected] , (United Kingdom)
  • 2 Department of Stem Cell Biology, Centre for Biomolecular Sciences, University of Nottingham, NG7 2RD, United Kingdom. , (United Kingdom)
  • 3 Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom. , (United Kingdom)
Type
Published Article
Journal
Biochimica et Biophysica Acta
Publisher
Elsevier
Publication Date
July 2016
Volume
1863
Issue
7 Pt B
Pages
1728–1748
Identifiers
DOI: 10.1016/j.bbamcr.2015.10.014
PMID: 26524115
Source
Medline
Keywords
License
Unknown

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.

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