The use of human induced pluripotent stem cell-derived atrial cardiomyocytes for studying arrhythmia mechanisms

Doctoranda: Marilù Casini
Dirigida por: Dra. Pilar Sepúlveda Sanchis, Dra. Imelda Ontoria Oviedo y Dr. Andreu Martínez Climent

Grupo de Investigación en Regeneración y Trasplante Cardíaco

Lugar de la defensa: UPV – Edificio departamental de ingeniería electrónica, planta 5, salón de grados 

Modalidad: Híbrida

SEGUIR ONLINE

Each year hundreds of thousands of new cases worldwide are annually diagnosed with atrial fibrillation (AF), estimating that approximately 33.5 million of people worldwide live with this complex disease. However, it became clear that AF is not only a prevalent cardiac arrhythmia but also a multifaceted and progressive
one. Thus, the development of new experimental models that recapitulate this complex mechanism is required. 

For this reason, this thesis has navigated through the intricate landscape of AF remodeling under an electrophysiological, structural and immunological point of view using an in vitro model of human induced pluripotent stem cell-derived atrial cardiomyocytes (hiPSC-aCM). The model showed to be able to recapitulate re-entry mechanisms as well as genetic remodeling correlated to electrophysiological, structural and immunological changes similar to those observed in AF patients, demonstrating its value as model for studying initiation arrhythmia mechanisms. Furthermore, the thesis explored innovative optogenetic approaches for action potential perturbation in hiPSC-aCM, demonstrating their
possible use for arrhythmia termination.

In conclusion, this PhD thesis makes a significant contribution to the development and testing of a new human atrial in vitro model of AF, providing a strong basis for future improvements of therapeutic target and drugs

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