A mathematical model of hiPSC cardiomyocytes electromechanics

Abstract Human induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) are becoming instrumental in cardiac research, human‐based cell level cardiotoxicity tests, and developing patient‐specific care. As one of the principal functional readouts is contractility, we propose a novel electrome...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Mohamadamin Forouzandehmehr, Jussi T. Koivumäki, Jari Hyttinen, Michelangelo Paci
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	action potential contractility drug test human stem cell‐derived cardiomyocyte immature cardiomyocytes in silico modeling Physiology QP1-981
Acceso en línea:	https://doaj.org/article/2a213b8ef80e404eb25942c944d75b20
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:2a213b8ef80e404eb25942c944d75b20
record_format	dspace
spelling	oai:doaj.org-article:2a213b8ef80e404eb25942c944d75b202021-11-27T15:48:30ZA mathematical model of hiPSC cardiomyocytes electromechanics2051-817X10.14814/phy2.15124https://doaj.org/article/2a213b8ef80e404eb25942c944d75b202021-11-01T00:00:00Zhttps://doi.org/10.14814/phy2.15124https://doaj.org/toc/2051-817XAbstract Human induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) are becoming instrumental in cardiac research, human‐based cell level cardiotoxicity tests, and developing patient‐specific care. As one of the principal functional readouts is contractility, we propose a novel electromechanical hiPSC‐CM computational model named the hiPSC‐CM‐CE. This model comprises a reparametrized version of contractile element (CE) by Rice et al., 2008, with a new passive force formulation, integrated into a hiPSC‐CM electrophysiology formalism by Paci et al. in 2020. Our simulated results were validated against in vitro data reported for hiPSC‐CMs at matching conditions from different labs. Specifically, key action potential (AP) and calcium transient (CaT) biomarkers simulated by the hiPSC‐CM‐CE model were within the experimental ranges. On the mechanical side, simulated cell shortening, contraction–relaxation kinetic indices (RT50 and RT25), and the amplitude of tension fell within the experimental intervals. Markedly, as an inter‐scale analysis, correct classification of the inotropic effects due to non‐cardiomyocytes in hiPSC‐CM tissues was predicted on account of the passive force expression introduced to the CE. Finally, the physiological inotropic effects caused by Verapamil and Bay‐K 8644 and the aftercontractions due to the early afterdepolarizations (EADs) were simulated and validated against experimental data. In the future, the presented model can be readily expanded to take in pharmacological trials and genetic mutations, such as those involved in hypertrophic cardiomyopathy, and study arrhythmia trigger mechanisms.Mohamadamin ForouzandehmehrJussi T. KoivumäkiJari HyttinenMichelangelo PaciWileyarticleaction potentialcontractilitydrug testhuman stem cell‐derived cardiomyocyteimmature cardiomyocytesin silico modelingPhysiologyQP1-981ENPhysiological Reports, Vol 9, Iss 22, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	action potential contractility drug test human stem cell‐derived cardiomyocyte immature cardiomyocytes in silico modeling Physiology QP1-981
spellingShingle	action potential contractility drug test human stem cell‐derived cardiomyocyte immature cardiomyocytes in silico modeling Physiology QP1-981 Mohamadamin Forouzandehmehr Jussi T. Koivumäki Jari Hyttinen Michelangelo Paci A mathematical model of hiPSC cardiomyocytes electromechanics
description	Abstract Human induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) are becoming instrumental in cardiac research, human‐based cell level cardiotoxicity tests, and developing patient‐specific care. As one of the principal functional readouts is contractility, we propose a novel electromechanical hiPSC‐CM computational model named the hiPSC‐CM‐CE. This model comprises a reparametrized version of contractile element (CE) by Rice et al., 2008, with a new passive force formulation, integrated into a hiPSC‐CM electrophysiology formalism by Paci et al. in 2020. Our simulated results were validated against in vitro data reported for hiPSC‐CMs at matching conditions from different labs. Specifically, key action potential (AP) and calcium transient (CaT) biomarkers simulated by the hiPSC‐CM‐CE model were within the experimental ranges. On the mechanical side, simulated cell shortening, contraction–relaxation kinetic indices (RT50 and RT25), and the amplitude of tension fell within the experimental intervals. Markedly, as an inter‐scale analysis, correct classification of the inotropic effects due to non‐cardiomyocytes in hiPSC‐CM tissues was predicted on account of the passive force expression introduced to the CE. Finally, the physiological inotropic effects caused by Verapamil and Bay‐K 8644 and the aftercontractions due to the early afterdepolarizations (EADs) were simulated and validated against experimental data. In the future, the presented model can be readily expanded to take in pharmacological trials and genetic mutations, such as those involved in hypertrophic cardiomyopathy, and study arrhythmia trigger mechanisms.
format	article
author	Mohamadamin Forouzandehmehr Jussi T. Koivumäki Jari Hyttinen Michelangelo Paci
author_facet	Mohamadamin Forouzandehmehr Jussi T. Koivumäki Jari Hyttinen Michelangelo Paci
author_sort	Mohamadamin Forouzandehmehr
title	A mathematical model of hiPSC cardiomyocytes electromechanics
title_short	A mathematical model of hiPSC cardiomyocytes electromechanics
title_full	A mathematical model of hiPSC cardiomyocytes electromechanics
title_fullStr	A mathematical model of hiPSC cardiomyocytes electromechanics
title_full_unstemmed	A mathematical model of hiPSC cardiomyocytes electromechanics
title_sort	mathematical model of hipsc cardiomyocytes electromechanics
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/2a213b8ef80e404eb25942c944d75b20
work_keys_str_mv	AT mohamadaminforouzandehmehr amathematicalmodelofhipsccardiomyocyteselectromechanics AT jussitkoivumaki amathematicalmodelofhipsccardiomyocyteselectromechanics AT jarihyttinen amathematicalmodelofhipsccardiomyocyteselectromechanics AT michelangelopaci amathematicalmodelofhipsccardiomyocyteselectromechanics AT mohamadaminforouzandehmehr mathematicalmodelofhipsccardiomyocyteselectromechanics AT jussitkoivumaki mathematicalmodelofhipsccardiomyocyteselectromechanics AT jarihyttinen mathematicalmodelofhipsccardiomyocyteselectromechanics AT michelangelopaci mathematicalmodelofhipsccardiomyocyteselectromechanics
_version_	1718408489026453504

A mathematical model of hiPSC cardiomyocytes electromechanics

Ejemplares similares