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Targeting the Immune System With Mesenchymal Stromal Cell-Derived Extracellular Vesicles: What Is the Cargo's Mechanism of Action?

The potent immunomodulatory activities displayed by mesenchymal stromal cells (MSCs) have motivated their application in hundreds of clinical trials to date. In some countries, they have subsequently been approved for the treatment of immune disorders such as Crohn's disease and graft-versus-ho...

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Autores principales: Martin-Rufino, Jorge Diego, Espinosa-Lara, Natalia, Osugui, Lika, Sanchez-Guijo, Fermin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856662/
https://www.ncbi.nlm.nih.gov/pubmed/31781552
http://dx.doi.org/10.3389/fbioe.2019.00308
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author Martin-Rufino, Jorge Diego
Espinosa-Lara, Natalia
Osugui, Lika
Sanchez-Guijo, Fermin
author_facet Martin-Rufino, Jorge Diego
Espinosa-Lara, Natalia
Osugui, Lika
Sanchez-Guijo, Fermin
author_sort Martin-Rufino, Jorge Diego
collection PubMed
description The potent immunomodulatory activities displayed by mesenchymal stromal cells (MSCs) have motivated their application in hundreds of clinical trials to date. In some countries, they have subsequently been approved for the treatment of immune disorders such as Crohn's disease and graft-versus-host disease. Increasing evidence suggests that their main mechanism of action in vivo relies on paracrine signaling and extracellular vesicles. Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) play a prominent role in intercellular communication by allowing the horizontal transfer of microRNAs, mRNAs, proteins, lipids and other bioactive molecules between MSCs and their targets. However, despite the considerable momentum gained by MSC-EV research, the precise mechanism by which MSC-EVs interact with the immune system is still debated. Available evidence is highly context-dependent and fragmentary, with a limited number of reports trying to link their efficacy to specific active components shuttled within them. In this concise review, currently available evidence on the molecular mechanisms underlying the effects of MSC-EV cargo on the immune system is analyzed. Studies that pinpoint specific MSC-EV-borne mediators of immunomodulation are highlighted, with a focus on the signaling events triggered by MSC-EVs in target immune cells. Reports that study the effects of preconditioning or “licensing” in MSC-EV-mediated immunomodulation are also presented. The need for further studies that dissect the mechanisms of MSC-EV cargo in the adaptive immune system is emphasized. Finally, the major challenges that need to be addressed to harness the full potential of these signaling vehicles are discussed, with the ultimate goal of effectively translating MSC-EV treatments into the clinic.
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spelling pubmed-68566622019-11-28 Targeting the Immune System With Mesenchymal Stromal Cell-Derived Extracellular Vesicles: What Is the Cargo's Mechanism of Action? Martin-Rufino, Jorge Diego Espinosa-Lara, Natalia Osugui, Lika Sanchez-Guijo, Fermin Front Bioeng Biotechnol Bioengineering and Biotechnology The potent immunomodulatory activities displayed by mesenchymal stromal cells (MSCs) have motivated their application in hundreds of clinical trials to date. In some countries, they have subsequently been approved for the treatment of immune disorders such as Crohn's disease and graft-versus-host disease. Increasing evidence suggests that their main mechanism of action in vivo relies on paracrine signaling and extracellular vesicles. Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) play a prominent role in intercellular communication by allowing the horizontal transfer of microRNAs, mRNAs, proteins, lipids and other bioactive molecules between MSCs and their targets. However, despite the considerable momentum gained by MSC-EV research, the precise mechanism by which MSC-EVs interact with the immune system is still debated. Available evidence is highly context-dependent and fragmentary, with a limited number of reports trying to link their efficacy to specific active components shuttled within them. In this concise review, currently available evidence on the molecular mechanisms underlying the effects of MSC-EV cargo on the immune system is analyzed. Studies that pinpoint specific MSC-EV-borne mediators of immunomodulation are highlighted, with a focus on the signaling events triggered by MSC-EVs in target immune cells. Reports that study the effects of preconditioning or “licensing” in MSC-EV-mediated immunomodulation are also presented. The need for further studies that dissect the mechanisms of MSC-EV cargo in the adaptive immune system is emphasized. Finally, the major challenges that need to be addressed to harness the full potential of these signaling vehicles are discussed, with the ultimate goal of effectively translating MSC-EV treatments into the clinic. Frontiers Media S.A. 2019-11-05 /pmc/articles/PMC6856662/ /pubmed/31781552 http://dx.doi.org/10.3389/fbioe.2019.00308 Text en Copyright © 2019 Martin-Rufino, Espinosa-Lara, Osugui and Sanchez-Guijo. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioengineering and Biotechnology
Martin-Rufino, Jorge Diego
Espinosa-Lara, Natalia
Osugui, Lika
Sanchez-Guijo, Fermin
Targeting the Immune System With Mesenchymal Stromal Cell-Derived Extracellular Vesicles: What Is the Cargo's Mechanism of Action?
title Targeting the Immune System With Mesenchymal Stromal Cell-Derived Extracellular Vesicles: What Is the Cargo's Mechanism of Action?
title_full Targeting the Immune System With Mesenchymal Stromal Cell-Derived Extracellular Vesicles: What Is the Cargo's Mechanism of Action?
title_fullStr Targeting the Immune System With Mesenchymal Stromal Cell-Derived Extracellular Vesicles: What Is the Cargo's Mechanism of Action?
title_full_unstemmed Targeting the Immune System With Mesenchymal Stromal Cell-Derived Extracellular Vesicles: What Is the Cargo's Mechanism of Action?
title_short Targeting the Immune System With Mesenchymal Stromal Cell-Derived Extracellular Vesicles: What Is the Cargo's Mechanism of Action?
title_sort targeting the immune system with mesenchymal stromal cell-derived extracellular vesicles: what is the cargo's mechanism of action?
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856662/
https://www.ncbi.nlm.nih.gov/pubmed/31781552
http://dx.doi.org/10.3389/fbioe.2019.00308
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