Publications by authors named "A Gepstein"
Article Synopsis
- Electroporation is a nonthermal method for treating cardiac arrhythmias, and this study aimed to create a functional in vitro model using human-induced pluripotent stem cells (hiPSCs) to explore its underlying mechanisms.
- Different pulsed-field ablation (PFA) protocols were tested on hiPSC-derived cardiac cells, revealing that PFA can create conduction block areas and demonstrated both reversible and irreversible electroporation effects.
- Findings indicated that high-frequency PFA was less effective than standard methods and that factors like pulse number and extracellular calcium levels influenced lesion size, with potential applications in controlling arrhythmic activity.
Heterozygous missense variants of the cardiac ryanodine receptor gene (RYR2) cause catecholaminergic polymorphic ventricular tachycardia (CPVT). These missense variants of RYR2 result in a gain of function of the ryanodine receptors, characterized by increased sensitivity to activation by calcium that results in an increased propensity to develop calcium waves and delayed afterdepolarizations. We have recently detected a nonsense variant in RYR2 in a young patient who suffered an unexplained cardiac arrest.
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- Optogenetics utilizes light-sensitive proteins to manipulate cardiac excitability, aiming to create high-resolution tools for controlling electrical activity in 2D and 3D human heart tissue models derived from induced pluripotent stem cells.
- Researchers combined opsin-carrying HEK293 cells with hiPSC-cardiomyocytes to create cardiac cell-sheets and engineered heart tissues, employing complex illumination patterns to evaluate and enhance electromechanical properties.
- The study demonstrated that optogenetics could effectively pace and synchronize heart tissue contraction while also providing a way to study and terminate arrhythmias, showing promising applications for cardiac resynchronization therapy.
Abnormal action potential (AP) properties, as occurs in long or short QT syndromes (LQTS and SQTS, respectively), can cause life-threatening arrhythmias. Optogenetics strategies, utilizing light-sensitive proteins, have emerged as experimental platforms for cardiac pacing, resynchronization, and defibrillation. We tested the hypothesis that similar optogenetic tools can modulate the cardiomyocyte's AP properties, as a potentially novel antiarrhythmic strategy.
View Article and Find Full Text PDFTissue engineering provides unique opportunities for disease modeling, drug testing, and regenerative medicine applications. The use of cell-seeded scaffolds to promote tissue development is the hallmark of the tissue engineering. Among the different types of scaffolds (derived from either natural or synthetic polymers) used in the field, the use of decellularized tissues/organs is specifically attractive.
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