title: Two dimensional electrophysiological characterization of human pluripotent stem cell-derived cardiomyocyte system.
abstract: Stem cell-derived cardiomyocytes provide a promising tool for human developmental biology, regenerative therapies, disease modeling, and drug discovery. As human pluripotent stem cell-derived cardiomyocytes remain functionally fetal-type, close monitoring of electrophysiological maturation is critical for their further application to biology and translation. However, to date, electrophysiological analyses of stem cell-derived cardiomyocytes has largely been limited by biologically undefined factors including 3D nature of embryoid body, sera from animals, and the feeder cells isolated from mouse. Large variability in the aforementioned systems leads to uncontrollable and irreproducible results, making conclusive studies difficult. In this report, a chemically-defined differentiation regimen and a monolayer cell culture technique was combined with multielectrode arrays for accurate, real-time, and flexible measurement of electrophysiological parameters in translation-ready human cardiomyocytes. Consistent with their natural counterpart, amplitude and dV/dtmaxof field potential progressively increased during the course of maturation. Monolayer culture allowed for the identification of pacemaking cells using the multielectrode array platform and thereby the estimation of conduction velocity, which gradually increased during the differentiation of cardiomyocytes. Thus, the electrophysiological maturation of the human pluripotent stem cell-derived cardiomyocytes in our system recapitulates in vivo development. This system provides a versatile biological tool to analyze human heart development, disease mechanisms, and the efficacy/toxicity of chemicals.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, USA.|California NanoSystems Institute, University of California, Los Angeles, USA.
authors.forename: Huanqi
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, USA.|California NanoSystems Institute, University of California, Los Angeles, USA.
authors.forename: Kelsey S
authors.initials: KS
authors.lastname: Scharnhorst
authors.affiliation: California NanoSystems Institute, University of California, Los Angeles, USA.|WPI Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science (NIMS), Japan.
authors.forename: Adam Z
authors.initials: AZ
authors.lastname: Stieg
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, USA.|California NanoSystems Institute, University of California, Los Angeles, USA.|WPI Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science (NIMS), Japan.|Jonsson Comprehensive Cancer Center, University of California, Los Angeles, USA.
authors.forename: James K
authors.initials: JK
authors.lastname: Gimzewski
authors.affiliation: Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Japan.
authors.forename: Itsunari
authors.initials: I
authors.lastname: Minami
authors.affiliation: Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Japan.|Institute for Frontier Medical Sciences, Kyoto University, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Nakatsuji
authors.affiliation: Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, USA.
authors.forename: Haruko
authors.initials: H
authors.lastname: Nakano
authors.affiliation: Jonsson Comprehensive Cancer Center, University of California, Los Angeles, USA.|Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, USA.|Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, USA.|Molecular Biology Institute, University of California, Los Angeles, USA.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakano
mesh_terms: D018929:Cell Culture Techniques; D002454:Cell Differentiation; D055724:Electrophysiological Phenomena; D006801:Humans; D032383:Myocytes, Cardiac / Q000502:physiology*; D039904:Pluripotent Stem Cells / Q000502:physiology*