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

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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 languageEnglish
Pages (from-to)1728-1748
Number of pages21
JournalBiochimica et Biophysica Acta
Volume1863
Issue number7
Early online date31 Oct 2015
DOIs
Publication statusPublished - 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

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