López, EstherMarinaro, Federicade Pedro, María de Los ÁngelesSánchez-Margallo, Francisco MiguelGomez-Serrano, MariaPonath, VivianePogge von Strandmann, ElkeJorge, InmaculadaVazquez, JesusFernández-Pereira, Luis MiguelCrisóstomo, VerónicaAlvarez, VeronicaCasado, Javier G2020-07-082020-07-082020-06Front Cell Dev Biol. 2020; 8:3212296-634Xhttp://hdl.handle.net/20.500.12105/10712Experimental data demonstrated that the regenerative potential and immunomodulatory capacity of cardiosphere-derived cells (CDCs) is mediated by paracrine mechanisms. In this process, extracellular vesicles derived from CDCs (EV-CDCs) are key mediators of their therapeutic effect. Considering the future applicability of these vesicles in human diseases, an accurate preclinical-to-clinical translation is needed, as well as an exhaustive molecular characterization of animal-derived therapeutic products. Based on that, the main goal of this study was to perform a comprehensive characterization of proteins and miRNAs in extracellular vesicles from porcine CDCs as a clinically relevant animal model. The analysis was performed by identification and quantification of proteins and miRNA expression profiles. Our results revealed the presence of clusters of immune-related and cardiac-related molecular biomarkers in EV-CDCs. Additionally, considering that priming stem cells with inflammatory stimuli may increase the therapeutic potential of released vesicles, here we studied the dynamic changes that occur in the extracellular vesicles from IFNγ-primed CDCs. These analyses detected statistically significant changes in several miRNAs and proteins. Notably, the increase in interleukin 6 (IL6) protein, as well as the increase in mir-125b (that targets IL6 receptor) was especially relevant. These results suggest a potential involvement of EV-CDCs in the regulation of the IL6/IL6R axis, with implications in inflammatory-mediated diseases.engVoRhttp://creativecommons.org/licenses/by/4.0/Atribución 4.0 Internacional32582685832110.3389/fcell.2020.00321Frontiers in cell and developmental biologyopen access