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Automatic optimization of an in silico model of human iPSC derived cardiomyocytes recapitulating calcium handling abnormalities

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Automatic optimization of an in silico model of human iPSC derived cardiomyocytes recapitulating calcium handling abnormalities. / Paci, Michelangelo; Pölönen, Risto-Pekka; Cori, Dario; Penttinen, Kirsi; Aalto-Setälä, Katriina; Severi, Stefano; Hyttinen, Jari.

In: Frontiers in Physiology, Vol. 9, No. JUN, 709, 26.06.2018.

Research output: Contribution to journalArticleScientificpeer-review

Harvard

Paci, M, Pölönen, R-P, Cori, D, Penttinen, K, Aalto-Setälä, K, Severi, S & Hyttinen, J 2018, 'Automatic optimization of an in silico model of human iPSC derived cardiomyocytes recapitulating calcium handling abnormalities', Frontiers in Physiology, vol. 9, no. JUN, 709. https://doi.org/10.3389/fphys.2018.00709

APA

Paci, M., Pölönen, R-P., Cori, D., Penttinen, K., Aalto-Setälä, K., Severi, S., & Hyttinen, J. (2018). Automatic optimization of an in silico model of human iPSC derived cardiomyocytes recapitulating calcium handling abnormalities. Frontiers in Physiology, 9(JUN), [709]. https://doi.org/10.3389/fphys.2018.00709

Vancouver

Paci M, Pölönen R-P, Cori D, Penttinen K, Aalto-Setälä K, Severi S et al. Automatic optimization of an in silico model of human iPSC derived cardiomyocytes recapitulating calcium handling abnormalities. Frontiers in Physiology. 2018 Jun 26;9(JUN). 709. https://doi.org/10.3389/fphys.2018.00709

Author

Paci, Michelangelo ; Pölönen, Risto-Pekka ; Cori, Dario ; Penttinen, Kirsi ; Aalto-Setälä, Katriina ; Severi, Stefano ; Hyttinen, Jari. / Automatic optimization of an in silico model of human iPSC derived cardiomyocytes recapitulating calcium handling abnormalities. In: Frontiers in Physiology. 2018 ; Vol. 9, No. JUN.

Bibtex - Download

@article{971f6f9d20574827b454fc5c8c550dcf,
title = "Automatic optimization of an in silico model of human iPSC derived cardiomyocytes recapitulating calcium handling abnormalities",
abstract = "The growing importance of human induced pluripotent stem cell-derived cardiomyoyctes (hiPSC-CMs), as patient-specific and disease-specific models for studying cellular cardiac electrophysiology or for preliminary cardiotoxicity tests, generated better understanding of hiPSC-CM biophysical mechanisms and great amount of action potential and calcium transient data. In this paper, we propose a new hiPSC-CM in silico model, with particular attention to Ca2+ handling. We used (i) the hiPSC-CM Paci2013 model as starting point, (ii) a new dataset of Ca2+ transient measurements to tune the parameters of the inward and outward Ca2+ fluxes of sarcoplasmic reticulum, and (iii) an automatic parameter optimization to fit action potentials and Ca2+ transients. The Paci2018 model simulates, together with the typical hiPSC-CM spontaneous action potentials, more refined Ca2+ transients and delayed afterdepolarizations-like abnormalities, which the old Paci2013 was not able to predict due to its mathematical formulation. The Paci2018 model was validated against (i) the same current blocking experiments used to validate the Paci2013 model, and (ii) recently published data about effects of different extracellular ionic concentrations. In conclusion, we present a new and more versatile in silico model, which will provide a platform for modeling the effects of drugs or mutations that affect Ca2+ handling in hiPSC-CMs.",
keywords = "Action potential, Calcium transient, Computer simulation, Human induced pluripotent stem cell-derived cardiomyocyte, In silico modeling",
author = "Michelangelo Paci and Risto-Pekka P{\"o}l{\"o}nen and Dario Cori and Kirsi Penttinen and Katriina Aalto-Set{\"a}l{\"a} and Stefano Severi and Jari Hyttinen",
note = "EXT={"}Penttinen, Kirsi{"}",
year = "2018",
month = "6",
day = "26",
doi = "10.3389/fphys.2018.00709",
language = "English",
volume = "9",
journal = "Frontiers in Physiology",
issn = "1664-042X",
publisher = "Frontiers",
number = "JUN",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Automatic optimization of an in silico model of human iPSC derived cardiomyocytes recapitulating calcium handling abnormalities

AU - Paci, Michelangelo

AU - Pölönen, Risto-Pekka

AU - Cori, Dario

AU - Penttinen, Kirsi

AU - Aalto-Setälä, Katriina

AU - Severi, Stefano

AU - Hyttinen, Jari

N1 - EXT="Penttinen, Kirsi"

PY - 2018/6/26

Y1 - 2018/6/26

N2 - The growing importance of human induced pluripotent stem cell-derived cardiomyoyctes (hiPSC-CMs), as patient-specific and disease-specific models for studying cellular cardiac electrophysiology or for preliminary cardiotoxicity tests, generated better understanding of hiPSC-CM biophysical mechanisms and great amount of action potential and calcium transient data. In this paper, we propose a new hiPSC-CM in silico model, with particular attention to Ca2+ handling. We used (i) the hiPSC-CM Paci2013 model as starting point, (ii) a new dataset of Ca2+ transient measurements to tune the parameters of the inward and outward Ca2+ fluxes of sarcoplasmic reticulum, and (iii) an automatic parameter optimization to fit action potentials and Ca2+ transients. The Paci2018 model simulates, together with the typical hiPSC-CM spontaneous action potentials, more refined Ca2+ transients and delayed afterdepolarizations-like abnormalities, which the old Paci2013 was not able to predict due to its mathematical formulation. The Paci2018 model was validated against (i) the same current blocking experiments used to validate the Paci2013 model, and (ii) recently published data about effects of different extracellular ionic concentrations. In conclusion, we present a new and more versatile in silico model, which will provide a platform for modeling the effects of drugs or mutations that affect Ca2+ handling in hiPSC-CMs.

AB - The growing importance of human induced pluripotent stem cell-derived cardiomyoyctes (hiPSC-CMs), as patient-specific and disease-specific models for studying cellular cardiac electrophysiology or for preliminary cardiotoxicity tests, generated better understanding of hiPSC-CM biophysical mechanisms and great amount of action potential and calcium transient data. In this paper, we propose a new hiPSC-CM in silico model, with particular attention to Ca2+ handling. We used (i) the hiPSC-CM Paci2013 model as starting point, (ii) a new dataset of Ca2+ transient measurements to tune the parameters of the inward and outward Ca2+ fluxes of sarcoplasmic reticulum, and (iii) an automatic parameter optimization to fit action potentials and Ca2+ transients. The Paci2018 model simulates, together with the typical hiPSC-CM spontaneous action potentials, more refined Ca2+ transients and delayed afterdepolarizations-like abnormalities, which the old Paci2013 was not able to predict due to its mathematical formulation. The Paci2018 model was validated against (i) the same current blocking experiments used to validate the Paci2013 model, and (ii) recently published data about effects of different extracellular ionic concentrations. In conclusion, we present a new and more versatile in silico model, which will provide a platform for modeling the effects of drugs or mutations that affect Ca2+ handling in hiPSC-CMs.

KW - Action potential

KW - Calcium transient

KW - Computer simulation

KW - Human induced pluripotent stem cell-derived cardiomyocyte

KW - In silico modeling

U2 - 10.3389/fphys.2018.00709

DO - 10.3389/fphys.2018.00709

M3 - Article

VL - 9

JO - Frontiers in Physiology

JF - Frontiers in Physiology

SN - 1664-042X

IS - JUN

M1 - 709

ER -