Electrophysiological Effects of Extracellular Vesicles Secreted by Cardiosphere-Derived Cells: Unraveling the Antiarrhythmic Properties of Cell Therapies

Processes

Ismael Hernández-Romero¹  AnaI. Fernández²  Francisco Fernández-Avilés²  Marina Moro-López²  Lidia Gómez-Cid²  Lilian Grigorian-Shamagian²  Susana Suárez-Sancho²  Felipe Atienza²  AnaS. de la Nava² 

[1] Department of Signal Theory and Communications, University Rey Juan Carlos, 28933 Fuenlabrada, Spain;Instituto de Investigación Sanitaria Gregorio Marañón, Hospital Gregorio Marañón, 28009 Madrid, Spain;

关键词: cell therapy;    extracellular vesicles;    antiarrhythmic effects;    optical mapping;    conduction velocity;   

DOI  :  10.3390/pr8080924

来源: DOAJ

【 摘 要 】

Although cell-based therapies show potential antiarrhythmic effects that could be mediated by their paracrine action, the mechanisms and the extent of these effects were not deeply explored. We investigated the antiarrhythmic mechanisms of extracellular vesicles secreted by cardiosphere-derived cell extracellular vesicles (CDC-EVs) on the electrophysiological properties and gene expression profile of HL1 cardiomyocytes. HL-1 cultures were primed with CDC-EVs or serum-free medium alone for 48 h, followed by optical mapping and gene expression analysis. In optical mapping recordings, CDC-EVs reduced the activation complexity of the cardiomyocytes by 40%, increased rotor meandering, and reduced rotor curvature, as well as induced an 80% increase in conduction velocity. HL-1 cells primed with CDC-EVs presented higher expression of SCN5A, CACNA1C, and GJA1, coding for proteins involved in I_Na, I_CaL, and Cx43, respectively. Our results suggest that CDC-EVs reduce activation complexity by increasing conduction velocity and modifying rotor dynamics, which could be driven by an increase in expression of SCN5A and CACNA1C genes, respectively. Our results provide new insights into the antiarrhythmic mechanisms of cell therapies, which should be further validated using other models.

【 授权许可】

Unknown