Automatic Optimization of an in Silico Model of Human iPSC Derived Cardiomyocytes Recapitulating Calcium Handling Abnormalities

Frontiers in Physiology
Michelangelo PaciJari Hyttinen

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 conclusio...Continue Reading

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Citations

Feb 8, 2020·Cardiovascular Research·Patrick M Boyle, Natalia A Trayanova
Aug 4, 2020·Royal Society Open Science·Charalampos SigalasRebecca A B Burton
Jan 22, 2021·Arteriosclerosis, Thrombosis, and Vascular Biology·Chi Keung Lam, Joseph C Wu
Dec 17, 2020·Journal of Cardiovascular Pharmacology·Michelangelo PaciJussi T Koivumäki
Mar 7, 2020·Cell Stem Cell·Arun SharmaClive N Svendsen
Feb 20, 2021·Mathematical Biosciences·Bogdan AmuzescuBeatrice Mihaela Radu
Oct 8, 2020·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Cesare CorradoSteven A Niederer
Jul 6, 2021·Frontiers in Physiology·Akwasi D AkwaboahMakarand Deo
Jul 3, 2021·International Journal of Molecular Sciences·Ana Da Silva CostaGodfrey L Smith
Nov 27, 2021·Physiological Reports·Mohamadamin ForouzandehmehrMichelangelo Paci

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Methods Mentioned

BETA
Assay

Software Mentioned

hiPSC
Matlab©
fminsearch
LiveAcquisition
CM

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