A Multiwell Cardiac μGMEA Platform for Action Potential Recordings from Human iPSC-Derived Cardiomyocyte Constructs

Stacie L. Edwards, Viviana Zlochiver, Donald B. Conrad, Ravi Vaidyanathan, Andrew M. Valiquette, Rosy Joshi-Mukherjee

Research output: Contribution to journalArticle

Abstract

Multielectrode array (MEA) technology has been extensively used for field potential recordings from excitable cells. However, its application for action potential (AP) measurements has not been harnessed. Here, we report a novel platform for high-resolution intracellular AP recordings from induced pluripotent stem cell-cardiomyocyte constructs derived from human cardiac fibroblasts. To gain intracellular access, micro-gold MEAs were used to electroporate multiple constructs simultaneously. High-throughput AP measurements were obtained from 41 multicellular constructs. Repeated electroporations of the same cells did not affect the signal stability. Our model has the capability to distinguish subtle differences in AP morphology to characterize the network profile. Furthermore, we confirm the reliability of the system by recapitulating known drug-induced physiological and arrhythmogenic responses. Overall, the model provides a unique cardio-electronic interface for non-invasive measurements of AP dynamics for drug screening and disease modeling. This technology opens the door for identifying novel cardio-factors to enhance electrophysiological maturation. Joshi-Mukherjee and colleagues introduce an alternative approach for non-invasive, long-term action potential (AP) measurements in cell networks for drug screening and disease modeling. The authors describe a novel platform for high-throughput AP recordings from the same cells over days on iPSC-cardiomyocytes constructs derived from human cardiac fibroblasts. This technology opens the door for identifying novel cardio-factors to enhance electrophysiological maturation.

Original languageEnglish (US)
Pages (from-to)522-536
Number of pages15
JournalStem Cell Reports
Volume11
Issue number2
DOIs
StatePublished - Aug 14 2018

Fingerprint

Cardiac Myocytes
Action Potentials
Fibroblasts
Screening
Throughput
Pharmaceutical Preparations
Preclinical Drug Evaluations
Technology
Stem cells
Gold
Induced Pluripotent Stem Cells
Electroporation

Keywords

  • action potentials
  • drug screening
  • field potentials
  • human cardiac fibroblasts
  • iPSC-derived cardiomyocytes
  • multielectrode array

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

Cite this

A Multiwell Cardiac μGMEA Platform for Action Potential Recordings from Human iPSC-Derived Cardiomyocyte Constructs. / Edwards, Stacie L.; Zlochiver, Viviana; Conrad, Donald B.; Vaidyanathan, Ravi; Valiquette, Andrew M.; Joshi-Mukherjee, Rosy.

In: Stem Cell Reports, Vol. 11, No. 2, 14.08.2018, p. 522-536.

Research output: Contribution to journalArticle

Edwards, Stacie L. ; Zlochiver, Viviana ; Conrad, Donald B. ; Vaidyanathan, Ravi ; Valiquette, Andrew M. ; Joshi-Mukherjee, Rosy. / A Multiwell Cardiac μGMEA Platform for Action Potential Recordings from Human iPSC-Derived Cardiomyocyte Constructs. In: Stem Cell Reports. 2018 ; Vol. 11, No. 2. pp. 522-536.
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