by Keyword: Extracellular vesicles
González-Callejo P, Gener P, Díaz-Riascos ZV, Conti S, Cámara-Sánchez P, Riera R, Mancilla S, García-Gabilondo M, Peg V, Arango D, Rosell A, Labernadie A, Trepat X, Albertazzi L, Schwartz S, Seras-Franzoso J, Abasolo I, (2023). Extracellular vesicles secreted by triple-negative breast cancer stem cells trigger premetastatic niche remodeling and metastatic growth in the lungs International Journal Of Cancer 152, 2153-2165 
Tumor secreted extracellular vesicles (EVs) are potent intercellular signaling platforms. They are responsible for the accommodation of the premetastatic niche (PMN) to support cancer cell engraftment and metastatic growth. However, complex cancer cell composition within the tumor increases also the heterogeneity among cancer secreted EVs subsets, a functional diversity that has been poorly explored. This phenomenon is particularly relevant in highly plastic and heterogenous triple-negative breast cancer (TNBC), in which a significant representation of malignant cancer stem cells (CSCs) is displayed. Herein, we selectively isolated and characterized EVs from CSC or differentiated cancer cells (DCC; EVsCSC and EVsDCC , respectively) from the MDA-MB-231 TNBC cell line. Our results showed that EVsCSC and EVsDCC contain distinct bioactive cargos and therefore elicit a differential effect on stromal cells in the TME. Specifically, EVsDCC activated secretory cancer associated fibroblasts (CAFs), triggering IL-6/IL-8 signaling and sustaining CSC phenotype maintenance. Complementarily, EVsCSC promoted the activation of α-SMA+ myofibroblastic CAFs subpopulations and increased the endothelial remodeling, enhancing the invasive potential of TNBC cells in vitro and in vivo. In addition, solely the EVsCSC mediated signaling prompted the transformation of healthy lungs into receptive niches able to support metastatic growth of breast cancer cells.© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
JTD Keywords: chemoresistance, dormancy, drives, extracellular vesicles, invasion, plasticity, premetastatic niche, triple-negative breast cancer, tumor microenvironment, Cancer cell plasticity, Extracellular vesicles, Fibroblasts, Premetastatic niche, Triple-negative breast cancer, Tumor microenvironment
Ulldemolins A, Jurado A, Herranz-Diez C, Gavara N, Otero J, Farré R, Almendros I, (2022). Lung Extracellular Matrix Hydrogels-Derived Vesicles Contribute to Epithelial Lung Repair Polymers 14, 4907
The use of physiomimetic decellularized extracellular matrix-derived hydrogels is attracting interest since they can modulate the therapeutic capacity of numerous cell types, including mesenchymal stromal cells (MSCs). Remarkably, extracellular vesicles (EVs) derived from MSCs display similar functions as their parental cells, mitigating tissue damage in lung diseases. However, recent data have shown that ECM-derived hydrogels could release other resident vesicles similar to EVs. Here, we aim to better understand the contribution of EVs and ECM-vesicles released from MSCs and/or lung-derived hydrogel (L-HG) in lung repair by using an in vitro lung injury model. L-HG derived-vesicles and MSCs EVs cultured either in L-HG or conventional plates were isolated and characterized. The therapeutic capacity of vesicles obtained from each experimental condition was tested by using an alveolar epithelial wound-healing assay. The number of ECM-vesicles released from acellular L-HG was 10-fold greater than EVs from conventional MSCs cell culture revealing that L-HG is an important source of bioactive vesicles. MSCs-derived EVs and L-HG vesicles have similar therapeutic capacity in lung repair. However, when wound closure rate was normalized by total proteins, the MSCs-derived EVs shows higher therapeutic potential to those released by L-HG. The EVs released from L-HG must be considered when HG is used as substrate for cell culture and EVs isolation.
JTD Keywords: cell, extracellular vesicles, hydrogel, lung epithelial cells, lung repair, mesenchymal stem cells, Extracellular matrix, Extracellular vesicles, Hydrogel, Lung epithelial cells, Lung repair, Mesenchymal stem cells, Respiratory-distress-syndrome
Georgiev VN, Avalos-Padilla Y, Fernàndez-Busquets X, Dimova R, (2022). Femtoliter Injection of ESCRT-III Proteins into Adhered Giant Unilamellar Vesicles Bio Protoc 12, e4328
The endosomal sorting complex required for transport (ESCRT) machinery mediates membrane fission reactions that exhibit a different topology from that observed in clathrin-coated vesicles. In all of the ESCRT-mediated events, the nascent vesicle buds away from the cytosol. However, ESCRT proteins are able to act upon membranes with different geometries. For instance, the formation of multivesicular bodies (MVBs) and the biogenesis of extracellular vesicles both require the participation of the ESCRT-III sub-complex, and they differ in their initial membrane geometry before budding starts: the protein complex acts either from outside the membrane organelle (causing inward budding) or from within (causing outward budding). Several studies have reconstituted the action of the ESCRT-III subunits in supported bilayers and cell-sized vesicles mimicking the geometry occurring during MVBs formation (in-bud), but extracellular vesicle budding (out-bud) mechanisms remain less explored, because of the outstanding difficulties encountered in encapsulation of functional ESCRT-III in vesicles. Here, we provide a different approach that allows the recreation of the out-bud formation, by combining giant unilamellar vesicles as a membrane model and a microinjection system. The vesicles are immobilized prior to injection via weak adhesion to the chamber coverslip, which also ensures preserving the membrane excess area required for budding. After protein injection, vesicles exhibit outward budding. The approach presented in this work can be used in the future to disentangle the mechanisms underlying ESCRT-III-mediated fission, recreating the geometry of extracellular bud production, which remains a challenge. Moreover, the microinjection methodology can be also adapted to interrogate the action of other cytosolic components on the encapsulating membranous organelle. Copyright: © 2022 The Authors.
JTD Keywords: adhesion, budding, electroformation, escrt-iii, exosomes, extracellular vesicles, light, microinjection, microparticles, plasma, Adhesion, Budding, Escrt-iii, Extracellular vesicles, Giant unilamellar vesicle (guv), Membrane, Microinjection
Cereta AD, Oliveira VR, Costa IP, Afonso JPR, Fonseca AL, de Souza ART, Silva GAM, Mello DACPG, Oliveira LVFd, da Palma RK, (2021). Emerging Cell-Based Therapies in Chronic Lung Diseases: What About Asthma? Frontiers In Pharmacology 12,
Asthma is a widespread disease characterized by chronic airway inflammation. It causes substantial disability, impaired quality of life, and avoidable deaths around the world. The main treatment for asthmatic patients is the administration of corticosteroids, which improves the quality of life; however, prolonged use of corticosteroids interferes with extracellular matrix elements. Therefore, cell-based therapies are emerging as a novel therapeutic contribution to tissue regeneration for lung diseases. This study aimed to summarize the advancements in cell therapy involving mesenchymal stromal cells, extracellular vesicles, and immune cells such as T-cells in asthma. Our findings provide evidence that the use of mesenchymal stem cells, their derivatives, and immune cells such as T-cells are an initial milestone to understand how emergent cell-based therapies are effective to face the challenges in the development, progression, and management of asthma, thus improving the quality of life.
JTD Keywords: asthma treatments, cell-based therapies, chronic lung diseases, extracellular vesicles, immune cells, mesenchymal stromal cells, Asthma treatments, Cell-based therapies, Chronic lung diseases, Extracellular vesicles, Immune cells, Mesenchymal stromal cells
Borgheti-Cardoso, L. N., Kooijmans, S. A. A., Gutiérrez Chamorro, L., Biosca, A., Lantero, E., Ramírez, M., Avalos-Padilla, Y., Crespo, I., Fernández, I., Fernandez-Becerra, C., del Portillo, H. A., Fernàndez-Busquets, X., (2020). Extracellular vesicles derived from Plasmodium-infected and non-infected red blood cells as targeted drug delivery vehicles International Journal of Pharmaceutics 587, 119627
Among several factors behind drug resistance evolution in malaria is the challenge of administering overall doses that are not toxic for the patient but that, locally, are sufficiently high to rapidly kill the parasites. Thus, a crucial antimalarial strategy is the development of drug delivery systems capable of targeting antimalarial compounds to Plasmodium with high specificity. In the present study, extracellular vesicles (EVs) have been evaluated as a drug delivery system for the treatment of malaria. EVs derived from naive red blood cells (RBCs) and from Plasmodium falciparum-infected RBCs (pRBCs) were isolated by ultrafiltration followed by size exclusion chromatography. Lipidomic characterization showed that there were no significant qualitative differences between the lipidomic profiles of pRBC-derived EVs (pRBC-EVs) and RBC-derived EVs (RBC-EVs). Both EVs were taken up by RBCs and pRBCs, although pRBC-EVs were more efficiently internalized than RBC-EVs, which suggested their potential use as drug delivery vehicles for these cells. When loaded into pRBC-EVs, the antimalarial drugs atovaquone and tafenoquine inhibited in vitro P. falciparum growth more efficiently than their free drug counterparts, indicating that pRBC-EVs can potentially increase the efficacy of several small hydrophobic drugs used for the treatment of malaria.
JTD Keywords: Antimalarial drugs, Drug delivery, Extracellular vesicles, Malaria, Plasmodium falciparum
Borgheti-Cardoso, L.N., Fernàndez-Busquets, X., (2018). Turning Plasmodium survival strategies against itself Future Medicinal Chemistry 10, (19), 2245-2248
