Erik Ernst

Comparison of cultured human cardiomyocyte clusters obtained from embryos/fetuses or derived from human embryonic stem cells

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

DOI

  • Søren Grubb, University of Copenhagen
  • ,
  • Maj Linea Vestergaard, University of Copenhagen
  • ,
  • Astrid Sten Andersen, University of Copenhagen
  • ,
  • Karen Koefoed Rasmussen, University of Copenhagen
  • ,
  • Linn Salto Mamsen, University of Copenhagen
  • ,
  • Greta Tuckute, University of Copenhagen
  • ,
  • Kristina Grunnet-Lauridsen, University of Copenhagen
  • ,
  • Kjeld Møllgård, University of Copenhagen
  • ,
  • Erik Ernst
  • Søren Tvorup Christensen, University of Copenhagen, Denmark
  • Kirstine Calloe, University of Copenhagen
  • ,
  • Claus Yding Andersen, University of Copenhagen

Cardiomyocytes (CMs) derived from human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs) are used to study cardiogenesis and mechanisms of heart disease, and are being used in methods for toxiological screening of drugs. The phenotype of stem-cell-derived CMs should ideally resemble native CMs. Here, we compare embryonic/fetal CMs with hESC-derived CMs according to function and morphology. CM clusters were obtained from human embryonic/fetal hearts from elective terminated pregnancies before gestational week 12, and separated into atrial and ventricular tissues. Specific markers for embryonic CMs and primary cilia were visualized using immunofluorescence microscopy analysis. Contracting human embryonic cardiomyocyte (hECM) clusters morphologically and phenotypically resemble CMs in the embryonic/fetal heart. In addition, the contracting hECM clusters expressed primary cilia similar to that of cells in the embryonic/fetal heart. The electrophysiological characteristics of atrial and ventricular CMs were established by recording action potentials (APs) using sharp electrodes. In contrast to ventricular APs, atrial APs displayed a marked early repolarization followed by a plateau phase. hESC-CMs displayed a continuum of AP shapes. In all embryonic/fetal clusters, both atrial and ventricular, AP duration was prolonged by exposure to the K V 11.1 channel inhibitor dofetilide (50 nM); however, the prolongation was not significant, possibly due to the relatively small number of experiments. This study provides novel information on APs and functional characteristics of atrial and ventricular CMs in first trimester hearts, and demonstrates that K v 11.1 channels play a functional role already at these early stages. These results provide information needed to validate methods being developed on the basis of in vitro-derived CMs from either hESC or iPSC, and although there was a good correlation between the morphology of the two types of CMs, differences in electrophysiological characteristics exist.

Original languageEnglish
JournalStem Cells and Development
Volume28
Issue9
Pages (from-to)608-619
Number of pages12
ISSN1547-3287
DOIs
Publication statusPublished - May 2019

    Research areas

  • action potential, cardiomyogenesis, heart development, hECM, hESC, iPSC, primary cilia

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