{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T19:38:23Z","timestamp":1791833903661,"version":"4.3.4"},"reference-count":73,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2025,5,11]],"date-time":"2025-05-11T00:00:00Z","timestamp":1746921600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,11]],"date-time":"2025-05-11T00:00:00Z","timestamp":1746921600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"\n Abstract<\/jats:title>\n \n Human\u2010induced pluripotent stem cell\u2010derived cardiomyocytes (hiPSC\u2010CMs) offer a transformative platform for\n in vitro<\/jats:italic>\n and\n in silico<\/jats:italic>\n testing of patient\u2010specific drugs, enabling detailed study of cardiac electrophysiology. By integrating standard experimental techniques with extracellular potential measurements from multi\u2010electrode arrays (MEAs), researchers can capture key tissue\u2010level electrophysiological properties, such as action potential dynamics and conduction characteristics. This study presents an innovative computational framework that combines an MEA\u2010based electrophysiological model with phenotype\u2010specific hiPSC\u2010CM ionic models, enabling accurate\n in silico<\/jats:italic>\n predictions of drug responses. We tested four drug compounds and ion channel blockers using this model and compared these predictions against experimental MEA data, establishing the model's robustness and reliability. Additionally, we examined how tissue heterogeneity in hiPSC\u2010CMs affects conduction velocity, providing insights into how cellular variations can influence drug efficacy and tissue\u2010level electrical behaviour. Our model was further tested through simulations of Brugada syndrome, successfully replicating pathological electrophysiological patterns observed in adult cardiac tissues. These findings highlight the potential of hiPSC\u2010CM MEA\u2010based\n in silico<\/jats:italic>\n modelling for advancing drug screening processes, which have the potential to refine disease\u2010specific therapy development, and improve patient outcomes in complex cardiac conditions.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n \n Human\u2010induced pluripotent stem cell\u2010derived cardiomyocytes (hiPSC\u2010CMs) offer a transformative platform for\n in vitro<\/jats:italic>\n and\n in silico<\/jats:italic>\n testing of patient\u2010specific drugs, enabling detailed study of cardiac electrophysiology.\n <\/jats:p>\n <\/jats:list-item>\n \n Development of an innovative computational framework that combines a multi\u2010electrode array (MEA)\u2010based electrophysiological model with phenotype\u2010specific hiPSC\u2010CM ionic models.<\/jats:p>\n <\/jats:list-item>\n \n Drug testing of four compounds and ion channel blockers using this hiPSC\u2010CM MEA model and comparison against experimental MEA data, establishing the model's robustness and reliability.<\/jats:p>\n <\/jats:list-item>\n \n Study of the effect of tissue heterogeneity in hiPSC\u2010CMs on conduction velocity, providing insights into how cellular variations can influence drug efficacy and tissue\u2010level electrical behaviour.<\/jats:p>\n <\/jats:list-item>\n \n Brugada syndrome simulation through the hiPSC\u2010CM MEA model, successfully replicating pathological electrophysiological patterns observed in adult cardiac tissues.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp287276","type":"journal-article","created":{"date-parts":[[2025,5,11]],"date-time":"2025-05-11T11:37:46Z","timestamp":1746963466000},"page":"8141-8166","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["In silico<\/i>\n modelling of multi\u2010electrode arrays for enhancing cardiac drug testing on hiPSC\u2010CM heterogeneous tissues"],"prefix":"10.1113","volume":"604","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7271-6943","authenticated-orcid":false,"given":"Sofia","family":"Botti","sequence":"first","affiliation":[{"name":"Euler Institute Universit\u00e0 della Svizzera Italiana Lugano Switzerland"},{"name":"Department of Mathematics \u201cFelice Casorati\u201d University of Pavia Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"Krause","sequence":"additional","affiliation":[{"name":"Euler Institute Universit\u00e0 della Svizzera Italiana Lugano Switzerland"},{"name":"Faculty of Mathematics and Informatics, UniDistance Brig Switzerland"},{"name":"AMCS, CEMSE, King Abdullah University of Science and Technology Thuwal Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3014-4668","authenticated-orcid":false,"given":"Luca F.","family":"Pavarino","sequence":"additional","affiliation":[{"name":"Department of Mathematics \u201cFelice Casorati\u201d University of Pavia Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2017.10.005"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-023-04674-9"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.668392"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.22489\/CinC.2017.022-271"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10123483"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2024.108899"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.3934\/acse.2023013"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2008.09.013"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2010.09.053"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2015.04.027"},{"key":"e_1_2_6_12_1","doi-asserted-by":"crossref","unstructured":"Cerneckis J. 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