Browsing by Author "Alcayaga-Miranda, Francisca"

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    Exosomes on the border of species and kingdom intercommunication
    (2019-08) Schuh, Christina; Cuenca, Jimena; Alcayaga-Miranda, Francisca; Khoury, Maroun
    Over the last decades exosomes have become increasingly popular in the field of medicine. While until recently they were believed to be involved in the removal of obsolete particles from the cell, it is now known that exosomes are key players in cellular communication, carrying source-specific molecules such as proteins, growth factors, miRNA/mRNA, among others. The discovery that exosomes are not bound to intraspecies interactions, but are also capable of interkingdom communication, has once again revolutionized the field of exosomes research. A rapidly growing body of literature is shedding light at novel sources and participation of exosomes in physiological or regenerative processes, infection and disease. For the purpose of this review we have categorized 6 sources of interest (animal products, body fluids, plants, bacteria, fungus and parasites) and linked their innate roles to the clinics and potential medical applications, such as cell-based therapy, diagnostics or drug delivery.
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    Gut Microbiota-Derived Extracellular Vesicles Influence Alcohol Intake Preferences in Rats
    (2025) Díaz-Ubilla, Macarena; Figueroa-Valdés, Aliosha I.; Tobar, Hugo E.; Quintanilla, María Elena; Díaz, Eugenio; Morales, Paola; Berríos-Cárcamo, Pablo; Santapau, Daniela; Gallardo, Javiera; Gregorio, Cristian de; Ugalde, Juan; Rojas, Carolina; Gonzalez-Madrid, Antonia; Ezquer, Marcelo; Israel, Yedy; Alcayaga-Miranda, Francisca; Ezquer, Fernando
    Growing preclinical and clinical evidence suggests a link between gutmicrobiota dysbiosis and problematic alcohol consumption. Extracellular vesicles (EVs) are key mediators involved in bacteria-to-host communication. However, their potential role in mediating addictive behaviour remains unexplored. This study investigates the role of gut microbiota-derived bacterial extracellular vesicles (bEVs) in driving high alcohol consumption. bEVs were isolated from the gut microbiota of a high alcoholdrinking rat strain (UChB rats), either ethanol-naïve or following chronic alcohol consumption and administered intraperitoneally or orally to alcohol-rejecting male and femaleWistar rats. Both types of UChB-derived bEVs increased Wistar’s voluntary alcohol consumption (three bottle choice test) up to 10-fold (p < 0.0001), indicating that bEVs are able and sufficient to transmit drinking behaviour across different rat strains. Molecular analysis revealed that bEVs administration did not induce systemic or brain inflammation in the recipient animals, suggesting that the increased alcohol intake triggered by UChB-derived bEVs operates through an inflammation-independent mechanism. Furthermore,we demonstrate that the vagus nerve mediates the bEV-induced increase in alcohol consumption, as bilateral vagotomy completely abolished the high drinking behaviour induced by both intraperitoneally injected and orally administered bEVs. Thus, this study identifies bEVs as a novel mechanism underlying gut microbiota-induced high alcohol intake in a vagus nerve-dependent manner.
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    Stem cell exosomes inhibit angiogenesis and tumor growth of oral squamous cell carcinoma
    (2019) Rosenberger, Leonie; Ezquer, Marcelo; Lillo-Vera, Fernando; Pedraza, Paulina L.; Ortúzar, María Ignacia; González, Paz L.; Figueroa-Valdés, Aliosha I.; Cuenca, Jimena; Ezquer, Fernando; Khoury, Maroun; Alcayaga-Miranda, Francisca
    Recently, exosomes secreted by menstrual mesenchymal stem cells have been identified as inhibitory agents of tumor angiogenesis and modulators of the tumor cell secretome in prostate and breast cancer. However, their direct effect on endothelial cells and paracrine mediators have not yet been investigated. Using a carrier-based cell culture system to test the scalability for exosome production, we showed that different types of endothelial cells present specific kinetics for exosomes internalization. Exosome-treatment of endothelial cells increased cytotoxicity and reduced VEGF secretion and angiogenesis in a dose-dependent manner. Using the hamster buccal pouch carcinoma as a preclinical model for human oral squamous cell carcinoma, we demonstrated a significant antitumor effect of intra-tumoral injection of exosomes associated with a loss of tumor vasculature. These results address up-scaling of exosome production, a relevant issue for their clinical application, and also assess menstrual stem cell exosomes as potential anti-angiogenic agents for the treatment of neoplastic conditions.

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