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Small Extracellular Vesicles Derived From MSCs Have Immunomodulatory Effects to Enhance Delivery of ASO-210 for Psoriasis Treatment
Mesenchymal stem cells (MSCs) have been increasingly used for treating autoimmune diseases due to their immune modulation functions, but inefficient homing to the target tissue and safety issues limits their wide application. Recently, increasing studies demonstrate small extracellular vesicles (sEV...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8960430/ https://www.ncbi.nlm.nih.gov/pubmed/35359454 http://dx.doi.org/10.3389/fcell.2022.842813 |
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author | Zhang, Weixian Lin, Jingxiong Shi, Peilin Su, Dandan Cheng, Xiaoli Yi, Wenkai Yan, Jian Chen, Hongbo Cheng, Fang |
author_facet | Zhang, Weixian Lin, Jingxiong Shi, Peilin Su, Dandan Cheng, Xiaoli Yi, Wenkai Yan, Jian Chen, Hongbo Cheng, Fang |
author_sort | Zhang, Weixian |
collection | PubMed |
description | Mesenchymal stem cells (MSCs) have been increasingly used for treating autoimmune diseases due to their immune modulation functions, but inefficient homing to the target tissue and safety issues limits their wide application. Recently, increasing studies demonstrate small extracellular vesicles (sEVs) as key mediators of MSCs to exert their immunomodulatory effects. In this study, we found that sEVs derived from human umbilical cord MSCs stimulated by IFN-γ (IFNγ-sEVs) inhibited proliferation and activation of peripheral blood mononuclear cells and T cells in vitro. Furthermore, we confirmed that IFNγ-sEVs reduced psoriasis symptoms including thickness, erythema, and scales of skin lesions; exhausted Th17 cells, increased Th2 cells; and reduced enrichment of inflammatory cytokines such as IL-17A, IFN-γ, IL-6, and TNF-α in both spleen and skin lesions in vivo. Importantly, IFNγ-sEVs significantly improved the delivery efficiency and stability of ASO-210, the antisense oligonucleotides of miR-210 block the immune imbalance and subsequent psoriasis development. Our results reveal MSC-sEVs as promising cell-free therapeutic agents and ideal delivery vehicles of antisense oligonucleotides for psoriasis treatment. |
format | Online Article Text |
id | pubmed-8960430 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89604302022-03-30 Small Extracellular Vesicles Derived From MSCs Have Immunomodulatory Effects to Enhance Delivery of ASO-210 for Psoriasis Treatment Zhang, Weixian Lin, Jingxiong Shi, Peilin Su, Dandan Cheng, Xiaoli Yi, Wenkai Yan, Jian Chen, Hongbo Cheng, Fang Front Cell Dev Biol Cell and Developmental Biology Mesenchymal stem cells (MSCs) have been increasingly used for treating autoimmune diseases due to their immune modulation functions, but inefficient homing to the target tissue and safety issues limits their wide application. Recently, increasing studies demonstrate small extracellular vesicles (sEVs) as key mediators of MSCs to exert their immunomodulatory effects. In this study, we found that sEVs derived from human umbilical cord MSCs stimulated by IFN-γ (IFNγ-sEVs) inhibited proliferation and activation of peripheral blood mononuclear cells and T cells in vitro. Furthermore, we confirmed that IFNγ-sEVs reduced psoriasis symptoms including thickness, erythema, and scales of skin lesions; exhausted Th17 cells, increased Th2 cells; and reduced enrichment of inflammatory cytokines such as IL-17A, IFN-γ, IL-6, and TNF-α in both spleen and skin lesions in vivo. Importantly, IFNγ-sEVs significantly improved the delivery efficiency and stability of ASO-210, the antisense oligonucleotides of miR-210 block the immune imbalance and subsequent psoriasis development. Our results reveal MSC-sEVs as promising cell-free therapeutic agents and ideal delivery vehicles of antisense oligonucleotides for psoriasis treatment. Frontiers Media S.A. 2022-03-10 /pmc/articles/PMC8960430/ /pubmed/35359454 http://dx.doi.org/10.3389/fcell.2022.842813 Text en Copyright © 2022 Zhang, Lin, Shi, Su, Cheng, Yi, Yan, Chen and Cheng. https://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 | Cell and Developmental Biology Zhang, Weixian Lin, Jingxiong Shi, Peilin Su, Dandan Cheng, Xiaoli Yi, Wenkai Yan, Jian Chen, Hongbo Cheng, Fang Small Extracellular Vesicles Derived From MSCs Have Immunomodulatory Effects to Enhance Delivery of ASO-210 for Psoriasis Treatment |
title | Small Extracellular Vesicles Derived From MSCs Have Immunomodulatory Effects to Enhance Delivery of ASO-210 for Psoriasis Treatment |
title_full | Small Extracellular Vesicles Derived From MSCs Have Immunomodulatory Effects to Enhance Delivery of ASO-210 for Psoriasis Treatment |
title_fullStr | Small Extracellular Vesicles Derived From MSCs Have Immunomodulatory Effects to Enhance Delivery of ASO-210 for Psoriasis Treatment |
title_full_unstemmed | Small Extracellular Vesicles Derived From MSCs Have Immunomodulatory Effects to Enhance Delivery of ASO-210 for Psoriasis Treatment |
title_short | Small Extracellular Vesicles Derived From MSCs Have Immunomodulatory Effects to Enhance Delivery of ASO-210 for Psoriasis Treatment |
title_sort | small extracellular vesicles derived from mscs have immunomodulatory effects to enhance delivery of aso-210 for psoriasis treatment |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8960430/ https://www.ncbi.nlm.nih.gov/pubmed/35359454 http://dx.doi.org/10.3389/fcell.2022.842813 |
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