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Generation of Ventricular-Like HiPSC-Derived Cardiomyocytes and High-Quality Cell Preparations for Calcium Handling Characterization
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Automatic Optimization of an in Silico Model of Human iPSC Derived Cardiomyocytes Recapitulating Calcium Handling

Michelangelo Paci1, Risto-Pekka Pölönen2, Dario Cori3

  • 1Faculty of Biomedical Sciences and Engineering, BioMediTech Institute, Tampere University of Technology, Tampere, Finland.

Frontiers in Physiology
|July 13, 2018
PubMed

Insights

A new computational model, Paci2018, enhances understanding of human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) function. This model accurately simulates calcium handling and action potentials, improving cardiac electrophysiology research.

Area of Science:

  • Computational biology
  • Cardiovascular research
  • Stem cell science

Background:

  • Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are crucial for studying cardiac electrophysiology and cardiotoxicity.
  • Existing models provide significant data but have limitations in accurately simulating complex biophysical mechanisms, particularly calcium handling.

Purpose of the Study:

  • To develop a novel *in silico* model of hiPSC-CMs with improved calcium handling simulation.
  • To refine the prediction of cardiac electrophysiological abnormalities, such as delayed afterdepolarizations.
  • To create a versatile platform for drug and mutation effect modeling in hiPSC-CMs.

Main Methods:

  • Utilized the Paci2013 hiPSC-CM model as a foundation.
  • Incorporated a new dataset of calcium transient measurements to optimize sarcoplasmic reticulum calcium flux parameters.
  • Employed automatic parameter optimization to fit action potentials and calcium transients.

Main Results:

  • The Paci2018 model accurately simulates typical hiPSC-CM spontaneous action potentials.
  • It provides more refined calcium transients and predicts abnormalities like delayed afterdepolarizations, which the previous model could not.
  • Validation against current-blocking experiments and varying extracellular ionic concentrations confirmed model accuracy.

Conclusions:

  • The Paci2018 model represents a significant advancement in *in silico* modeling of hiPSC-CMs.
  • It offers enhanced capabilities for simulating calcium handling and predicting electrophysiological abnormalities.
  • This model serves as a valuable platform for investigating the impact of drugs and genetic mutations on cardiac cells.

Keywords:
action potentialcalcium transientcomputer simulationhuman induced pluripotent stem cell-derived cardiomyocytein silico modeling

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