ヒトiPS細胞由来心筋細胞シートの不整脈研究への応用可能性:<I>in silico</I>不整脈学の観点から  [in Japanese] Applicability of Human Induced Pluripotent Stem Cell-derived Myocardial Sheet to the Study of Arrhythmias:From the Viewpoint of <I>in silico</I> Arrhythmology  [in Japanese]

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Author(s)

    • 芦原 貴司 ASHIHARA Takashi
    • 滋賀医科大学循環器内科・不整脈センター Department of Cardiovascular Medicine, Heart Rhythm Center, Shiga University of Medical Science
    • 黒川 洵子 KUROKAWA Junko
    • 東京医科歯科大学難治疾患研究所生体情報薬理学分野 Department of Bio-informational Pharmacology, Tokyo Medical and Dental University, MRI
    • 堀江 稔 HORIE Minoru
    • 滋賀医科大学循環器内科・不整脈センター Department of Cardiovascular Medicine, Heart Rhythm Center, Shiga University of Medical Science

Abstract

<B>Background</B>: Recently, myocardial sheets consisting of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) have been used to clarify the mechanisms of inherited arrhythmias and to evaluate the efficacy of antiarrhythmic drugs. However, whether the electrophysiological properties of the hiPSC-CM are the same as those of the original human cardiomyocytes (hCM) remains unclear. Indeed, hiPSC-CM has automaticity, longer action potential duration (APD), smaller action potential amplitude (APA), and positively shifted diastolic potential (DP). <B>Methods</B>: To clarify this issue, we constructed <I>in silico</I> models of hCM and hiPSC-CM sheets based on the experimental data, and performed simulations of spiral wave (SW) reentry. Then we analyzed the SW behaviors in the <I>in silico</I> myocardial sheets, and also evaluated the effects of <i>I</i><sub>Kr</sub> blockade. <B>Results</B>: ( 1 )The <I>in silico</I> model of hiPSC-CM had spontaneous activations 0.5-1 Hz, longer APD, smaller APA, and DP positively shifted by∼15 mV. ( 2 )Conduction velocity (CV) in the hiPSC-CM sheet was∼5 cm/s, which was only∼1/10 of the CV in the hCM sheet. ( 3 )Mean cycle length (mCL) of excitations during SW reentry in the hiPSC-CM sheet was∼0.9 Hz, whereas that in the hCM sheet was∼5 Hz and identical to that of human VF. ( 4 )Both CV and mCL during SW reentry in the model of hiPSC-CM sheet were highly consistent with previous experimental data. ( 5 )The mCL of SW reentry in hCM sheet was markedly prolonged by <i>I</i><sub>Kr</sub> blockade, whereas that in hiPSC-CM sheet was shortened. <B>Conclusion</B>: The SW behavior and the antiarrhythmic drug efficacy in the <I>in silico</I> models of hCM and hiPSC-CM sheets are different. Our findings suggest that such <I>in silico</I> analytical approach might fill the gap between hCM and hiPSC-CM when we apply the hiPSC-CM sheet to clinical practice.

Journal

  • Transactions of Japanese Society for Medical and Biological Engineering

    Transactions of Japanese Society for Medical and Biological Engineering 53(3), 100-105, 2015

    Japanese Society for Medical and Biological Engineering

Codes

  • NII Article ID (NAID)
    130005106893
  • NII NACSIS-CAT ID (NCID)
    AA11633569
  • Text Lang
    JPN
  • ISSN
    1347-443X
  • NDL Article ID
    026685211
  • NDL Call No.
    Z19-108
  • Data Source
    NDL  J-STAGE 
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