Simultaneous voltage and calcium mapping of genetically purified human induced pluripotent stem cell-derived cardiac myocyte monolayers

Peter Lee, Matt Klos, Christian Bollensdorff, Luqia Hou, Paul Ewart, Timothy J. Kamp, Jianhua Zhang, Alexandra Bizy, Guadalupe Guerrero-Serna, Peter Kohl, José Jalife, Todd J. Herron

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104 Citations (Scopus)

Abstract

Rationale: Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) offer a powerful in vitro tool to investigate disease mechanisms and to perform patient-specific drug screening. To date, electrophysiological analysis of iPSC-CMs has been limited to single-cell recordings or low-resolution microelectrode array mapping of small cardiomyocyte aggregates. New methods of generating and optically mapping impulse propagation of large human iPSC-CM cardiac monolayers are needed. Objective: Our first aim was to develop an imaging platform with versatility for multiparameter electrophysiological mapping of cardiac preparations, including human iPSC-CM monolayers. Our second aim was to create large electrically coupled human iPSC-CM monolayers for simultaneous action potential and calcium wave propagation measurements. Methods and Results: A fluorescence imaging platform based on electronically controlled light-emitting diode illumination, a multiband emission filter, and single camera sensor was developed and utilized to monitor simultaneously action potential and intracellular calcium wave propagation in cardiac preparations. Multiple, large-diameter (≥1 cm), electrically coupled human cardiac monolayers were then generated that propagated action potentials and calcium waves at velocities similar to those commonly observed in rodent cardiac monolayers. Conclusions: The multiparametric imaging system presented here offers a scalable enabling technology to measure simultaneously action potential and intracellular calcium wave amplitude and dynamics of cardiac monolayers. The advent of large-scale production of human iPSC-CMs makes it possible to now generate sufficient numbers of uniform cardiac monolayers that can be utilized for the study of arrhythmia mechanisms and offers advantages over commonly used rodent models.

Original languageEnglish
Pages (from-to)1556-1563
Number of pages8
JournalCirculation Research
Volume110
Issue number12
DOIs
Publication statusPublished - 8 Jun 2012
Externally publishedYes

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Keywords

  • Arrhythmia research
  • Bioengineering
  • Cardiac regeneration
  • Induced pluripotent stem cells
  • Optical mapping

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Lee, P., Klos, M., Bollensdorff, C., Hou, L., Ewart, P., Kamp, T. J., Zhang, J., Bizy, A., Guerrero-Serna, G., Kohl, P., Jalife, J., & Herron, T. J. (2012). Simultaneous voltage and calcium mapping of genetically purified human induced pluripotent stem cell-derived cardiac myocyte monolayers. Circulation Research, 110(12), 1556-1563. https://doi.org/10.1161/CIRCRESAHA.111.262535