Electrophysiological analysis of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) using multi-electrode arrays (MEAs)

Luca Sala, Dorien Ward-van Oostwaard, Leon G.J. Tertoolen, Christine L. Mummery, Milena Bellin

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Cardiomyocytes can now be derived with high efficiency from both human embryonic and human induced-Pluripotent Stem Cells (hPSC). hPSC-derived cardiomyocytes (hPSC-CMs) are increasingly recognized as having great value for modeling cardiovascular diseases in humans, especially arrhythmia syndromes. They have also demonstrated relevance as in vitro systems for predicting drug responses, which makes them potentially useful for drug-screening and discovery, safety pharmacology and perhaps eventually for personalized medicine. This would be facilitated by deriving hPSC-CMs from patients or susceptible individuals as hiPSCs. For all applications, however, precise measurement and analysis of hPSC-CM electrical properties are essential for identifying changes due to cardiac ion channel mutations and/or drugs that target ion channels and can cause sudden cardiac death. Compared with manual patch-clamp, multi-electrode array (MEA) devices offer the advantage of allowing medium- to high-throughput recordings. This protocol describes how to dissociate 2D cell cultures of hPSC-CMs to small aggregates and single cells and plate them on MEAs to record their spontaneous electrical activity as field potential. Methods for analyzing the recorded data to extract specific parameters, such as the QT and the RR intervals, are also described here. Changes in these parameters would be expected in hPSC-CMs carrying mutations responsible for cardiac arrhythmias and following addition of specific drugs, allowing detection of those that carry a cardiotoxic risk.

Original languageEnglish
Article numbere55587
JournalJournal of visualized experiments
Volume2017
Issue number123
DOIs
Publication statusPublished - 12 May 2017

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Pluripotent Stem Cells
Stem cells
Cardiac Myocytes
Electrodes
Induced Pluripotent Stem Cells
Ion Channels
Pharmaceutical Preparations
Cardiac Arrhythmias
Precision Medicine
Mutation
Preclinical Drug Evaluations
Sudden Cardiac Death
Clamping devices
Ions
Drug Discovery
Cell culture
Medicine
Screening
Electric properties
Cardiovascular Diseases

Keywords

  • Cardiac arrhythmia
  • Developmental biology
  • Drug screening
  • Electrophysiology
  • Field potential
  • Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs)
  • Issue 123
  • Long QT syndrome
  • Micro-electrode arrays
  • Multi-electrode arrays
  • QT interval
  • RR interval
  • Safety pharmacology

Cite this

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abstract = "Cardiomyocytes can now be derived with high efficiency from both human embryonic and human induced-Pluripotent Stem Cells (hPSC). hPSC-derived cardiomyocytes (hPSC-CMs) are increasingly recognized as having great value for modeling cardiovascular diseases in humans, especially arrhythmia syndromes. They have also demonstrated relevance as in vitro systems for predicting drug responses, which makes them potentially useful for drug-screening and discovery, safety pharmacology and perhaps eventually for personalized medicine. This would be facilitated by deriving hPSC-CMs from patients or susceptible individuals as hiPSCs. For all applications, however, precise measurement and analysis of hPSC-CM electrical properties are essential for identifying changes due to cardiac ion channel mutations and/or drugs that target ion channels and can cause sudden cardiac death. Compared with manual patch-clamp, multi-electrode array (MEA) devices offer the advantage of allowing medium- to high-throughput recordings. This protocol describes how to dissociate 2D cell cultures of hPSC-CMs to small aggregates and single cells and plate them on MEAs to record their spontaneous electrical activity as field potential. Methods for analyzing the recorded data to extract specific parameters, such as the QT and the RR intervals, are also described here. Changes in these parameters would be expected in hPSC-CMs carrying mutations responsible for cardiac arrhythmias and following addition of specific drugs, allowing detection of those that carry a cardiotoxic risk.",
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Electrophysiological analysis of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) using multi-electrode arrays (MEAs). / Sala, Luca; Ward-van Oostwaard, Dorien; Tertoolen, Leon G.J.; Mummery, Christine L.; Bellin, Milena.

In: Journal of visualized experiments, Vol. 2017, No. 123, e55587, 12.05.2017.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Ward-van Oostwaard, Dorien

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AU - Mummery, Christine L.

AU - Bellin, Milena

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