Analysis of β-adrenergic receptor signaling in contractile function of human iPS cell-derived cardiomyocytes

DOI
  • KUNII Wataru
    Department of Bio-informational Pharmacology, University of Shizuoka
  • YAMAGUCHI Masahiko
    Department of Bio-informational Pharmacology, University of Shizuoka
  • SAKAMOTO Kazuho
    Department of Bio-informational Pharmacology, University of Shizuoka
  • KUROKAWA Junko
    Department of Bio-informational Pharmacology, University of Shizuoka

Bibliographic Information

Other Title
  • ヒトiPS細胞由来心筋細胞のβアドレナリン受容体シグナル調節の解析

Description

<p>Human iPS cell-derived cardiomyocytes (hiPSC-CMs) could be an unlimited source of human cardiomyocytes for pre-clinical safety assessment. Current approaches to evaluate cardiac contractile function in vitro are limited to low-throughput methods. Thus, we employ a novel method to evaluate cardiotoxicity in hiPSC-CMs. Motion field imaging (MFI; SI8000 Cell Motion Imaging System, SONY IP&S, Japan) was performed to observe contractile functions of spontaneously beating hiPSC-CMs. It has been known that hiPSC-CMs exhibit atrial- and ventricle-like electrophysiological properties. This variation could be a problem to test drug safety. To enhance accuracy of safety assessment, we tested whether the MFI method can discriminate cardiomyocytes expressing MLC2a (atrial marker) or MLC2v (ventricular marker). Human iPSC-CMs showed the same trends on contractile functions as neonatal mice cardiomyocytes, and each cell-type showed distinct regulations via β-adrenergic receptor signaling in iCell-cardiomyocytes (CDIJ Fujifilm, Japan), but similar in iCell-cardiomyocyte2 (CDIJ Fujifilm, Japan). These results suggest that cell-to-cell variation varies among cell lines.</p>

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