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Utilizing Human-Induced Pluripotent Stem Cells to Study Cardiac Electroporation Pulsed-Field Ablation
Leonid Maizels1,2,3,4, Eyal Heller1, Michal Landesberg5
1Division of Cardiology, Leviev Center of Cardiovascular Medicine, Sheba Medical Center, Ramt Gan, Israel (L.M., E.H., R.B., A.S., E.M.).
Circulation. Arrhythmia and Electrophysiology
|February 12, 2024
Summary
Pulsed-field ablation (PFA) in human cardiac tissue models shows potential for treating arrhythmias by creating conduction blocks. This study provides insights into PFA mechanisms and optimization for antiarrhythmic therapies.
Area of Science:
- Cardiovascular Research
- Biomedical Engineering
- Electrophysiology
Background:
- Pulsed-field ablation (PFA) is a promising nonthermal method for cardiac arrhythmia treatment.
- Knowledge gaps exist regarding the mechanisms and electrophysiological effects of cardiomyocyte electroporation.
- A functional in vitro model using human-induced pluripotent stem cells (hiPSCs)-derived cardiac tissue is needed.
Purpose of the Study:
- Establish and characterize a functional in vitro model of hiPSC-derived cardiac tissue.
- Investigate the fundamentals of cardiac PFA.
- Understand the mechanistic nature and electrophysiological consequences of cardiomyocyte electroporation.
Main Methods:
- hiPSC-derived cardiomyocytes were cultured as circular cell sheets.
- Cells were subjected to various PFA protocols.
- Optical mapping, cellular, and molecular characterizations were performed.
Main Results:
- PFA created electrically silenced lesions and conduction blocks in cardiac tissue models.
- Both reversible and irreversible electroporation components were observed, with reversibility up to 15 minutes.
- High-frequency PFA was less effective per pulse, but increased pulse number and extracellular Ca2+ augmented lesion size.
- Regulated cell death was identified as a key factor post-PFA.
- Sustainable conduction blocks were generated, demonstrating PFA's antiarrhythmic potential.
Conclusions:
- hiPSC-derived cardiac tissue is a suitable model for studying cardiac electroporation.
- This model facilitates PFA protocol optimization and investigation of PFA's antiarrhythmic properties.
- Novel insights into PFA temporal and electrophysiological characteristics were gained.
