In Silico Identification of the Key Ionic Currents Modulating Human Pluripotent Stem Cell-Derived Cardiomyocytes Towards an Adult Phenotype

Leto L. Riebel, Elisa Passini, Francesca Margara, Michelangelo Paci, Jacopo Biasetti, Blanca Rodriguez

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

Abstract

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provide a promising resource for regenerative therapies. However, their immature phenotype and heterogeneities raise concern for arrhythmia when hiPSC-CMs are inserted into the native tissue. In silico models can improve understanding of the electrophysiological differences between hiPSC-CMs and adult cardiomyocytes and inform risk predictions. Our aim is to conduct a sensitivity analysis to identify the main ionic currents determining differences in electrophysiological properties between the Paci2020 model (hiPSC-CMs) and the ToR-ORd model (human ventricular cardiomyocytes). Our simulations highlighted the fast $Na^{+}$ current as the key modulator of upstroke velocity, while the inward and rapid delayed rectifier $K^{+}$ currents mainly contributed to a decrease of diastolic potential and action potential duration, respectively. In conclusion, we identified an increase of the conductance of these currents essential to modulate the biomarkers of the hiPSC-CM model towards the adult phenotype.
Original languageEnglish
Title of host publication2021 Computing in Cardiology (CinC)
PublisherIEEE
Pages1-4
Number of pages4
ISBN (Electronic)978-1-6654-7916-5
DOIs
Publication statusPublished - 2021
Publication typeA4 Article in a conference publication
EventComputing in cardiology - , Czech Republic
Duration: 13 Sep 202115 Sep 2021

Publication series

NameComputing in cardiology
ISSN (Electronic)2325-887X

Conference

ConferenceComputing in cardiology
Country/TerritoryCzech Republic
Period13/09/2115/09/21

Keywords

  • Analytical models
  • Electric potential
  • Sensitivity analysis
  • Biological system modeling
  • Computational modeling
  • Rectifiers
  • Modulation

Publication forum classification

  • Publication forum level 1

Fingerprint

Dive into the research topics of 'In Silico Identification of the Key Ionic Currents Modulating Human Pluripotent Stem Cell-Derived Cardiomyocytes Towards an Adult Phenotype'. Together they form a unique fingerprint.

Cite this