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]

<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>_Kr 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>_Kr 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.