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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-11-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fbioe.2019.00308/full |
| _version_ | 1828387908428496896 |
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| author | Jorge Diego Martin-Rufino Jorge Diego Martin-Rufino Natalia Espinosa-Lara Lika Osugui Fermin Sanchez-Guijo Fermin Sanchez-Guijo Fermin Sanchez-Guijo |
| author_facet | Jorge Diego Martin-Rufino Jorge Diego Martin-Rufino Natalia Espinosa-Lara Lika Osugui Fermin Sanchez-Guijo Fermin Sanchez-Guijo Fermin Sanchez-Guijo |
| author_sort | Jorge Diego Martin-Rufino |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-10T06:03:25Z |
| format | Article |
| id | doaj.art-d8b13498c789450a9e992bbb6a3957d1 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-10T06:03:25Z |
| publishDate | 2019-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-d8b13498c789450a9e992bbb6a3957d12022-12-22T01:59:46ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852019-11-01710.3389/fbioe.2019.00308482639Targeting the Immune System With Mesenchymal Stromal Cell-Derived Extracellular Vesicles: What Is the Cargo's Mechanism of Action?Jorge Diego Martin-Rufino0Jorge Diego Martin-Rufino1Natalia Espinosa-Lara2Lika Osugui3Fermin Sanchez-Guijo4Fermin Sanchez-Guijo5Fermin Sanchez-Guijo6Unidad de Terapia Celular, Servicio de Hematología, IBSAL-Hospital Universitario de Salamanca, Salamanca, SpainFacultad de Medicina, Universidad de Salamanca, Salamanca, SpainUnidad de Terapia Celular, Servicio de Hematología, IBSAL-Hospital Universitario de Salamanca, Salamanca, SpainUnidad de Terapia Celular, Servicio de Hematología, IBSAL-Hospital Universitario de Salamanca, Salamanca, SpainUnidad de Terapia Celular, Servicio de Hematología, IBSAL-Hospital Universitario de Salamanca, Salamanca, SpainFacultad de Medicina, Universidad de Salamanca, Salamanca, SpainCentro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Salamanca, SpainThe 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.https://www.frontiersin.org/article/10.3389/fbioe.2019.00308/fullmesenchymal stromal cellsextracellular vesiclesimmune systemcell therapyregenerative medicinestem cells |
| spellingShingle | Jorge Diego Martin-Rufino Jorge Diego Martin-Rufino Natalia Espinosa-Lara Lika Osugui Fermin Sanchez-Guijo Fermin Sanchez-Guijo Fermin Sanchez-Guijo Targeting the Immune System With Mesenchymal Stromal Cell-Derived Extracellular Vesicles: What Is the Cargo's Mechanism of Action? Frontiers in Bioengineering and Biotechnology mesenchymal stromal cells extracellular vesicles immune system cell therapy regenerative medicine stem cells |
| 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 | mesenchymal stromal cells extracellular vesicles immune system cell therapy regenerative medicine stem cells |
| url | https://www.frontiersin.org/article/10.3389/fbioe.2019.00308/full |
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