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Human bone marrow mesenchymal stem cell-derived extracellular vesicles inhibit shoulder stiffness via let-7a/Tgfbr1 axis

Shoulder stiffness (SS) is a common shoulder disease characterized by increasing pain and limited range of motion. SS is considered to be an inflammatory and fibrotic disorder pathologically. However, there is no consensus on the most effective conservative treatment for fibrosis. Given that human B...

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Autores principales: Luo, Zhiwen, Sun, Yaying, Qi, Beijie, Lin, Jinrong, Chen, Yisheng, Xu, Yuzhen, Chen, Jiwu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: KeAi Publishing 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965035/
https://www.ncbi.nlm.nih.gov/pubmed/35386460
http://dx.doi.org/10.1016/j.bioactmat.2022.01.016
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author Luo, Zhiwen
Sun, Yaying
Qi, Beijie
Lin, Jinrong
Chen, Yisheng
Xu, Yuzhen
Chen, Jiwu
author_facet Luo, Zhiwen
Sun, Yaying
Qi, Beijie
Lin, Jinrong
Chen, Yisheng
Xu, Yuzhen
Chen, Jiwu
author_sort Luo, Zhiwen
collection PubMed
description Shoulder stiffness (SS) is a common shoulder disease characterized by increasing pain and limited range of motion. SS is considered to be an inflammatory and fibrotic disorder pathologically. However, there is no consensus on the most effective conservative treatment for fibrosis. Given that human Bone Marrow Mesenchymal Stem Cell-derived extracellular vesicles (BMSC-EVs) displayed promising therapeutic effects for various tissues, we investigated the therapeutic effect of BMSC-EVs on fibrosis in a mice immobilization model and two cell models. By conducting a series of experiments, we found that BMSC-EVs can significantly inhibit the fibrogenic process both in vitro and in vivo. In detail, BMSC-EVs suppressed the aberrant proliferation, high collagen production capacity, and activation of fibrotic pathways in TGF-β-stimulated fibroblasts in vitro. Besides, in vivo, BMSC-EVs reduced cell infiltration, reduced fibrotic tissue in the shoulder capsule, and improved shoulder mobility. In addition, via exosomal small RNA sequencing and qPCR analysis, let-7a-5p was verified to be the highest expressed miRNA with predicted antifibrotic capability in BMSC-EVs. The antifibrotic capacity of BMSC-EVs was significantly impaired after the knockdown of let-7a-5p. Moreover, we discovered that the mRNA of TGFBR1 (the membrane receptor of transforming growth factor β) was the target of let-7a-5p. Together, these findings elucidated the antifibrotic role of BMSC-EVs in shoulder capsular fibrosis. This study clarifies a new approach using stem cell-derived EVs therapy as an alternative to cell therapy, which may clinically benefit patients with SS in the future.
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spelling pubmed-89650352022-04-05 Human bone marrow mesenchymal stem cell-derived extracellular vesicles inhibit shoulder stiffness via let-7a/Tgfbr1 axis Luo, Zhiwen Sun, Yaying Qi, Beijie Lin, Jinrong Chen, Yisheng Xu, Yuzhen Chen, Jiwu Bioact Mater Article Shoulder stiffness (SS) is a common shoulder disease characterized by increasing pain and limited range of motion. SS is considered to be an inflammatory and fibrotic disorder pathologically. However, there is no consensus on the most effective conservative treatment for fibrosis. Given that human Bone Marrow Mesenchymal Stem Cell-derived extracellular vesicles (BMSC-EVs) displayed promising therapeutic effects for various tissues, we investigated the therapeutic effect of BMSC-EVs on fibrosis in a mice immobilization model and two cell models. By conducting a series of experiments, we found that BMSC-EVs can significantly inhibit the fibrogenic process both in vitro and in vivo. In detail, BMSC-EVs suppressed the aberrant proliferation, high collagen production capacity, and activation of fibrotic pathways in TGF-β-stimulated fibroblasts in vitro. Besides, in vivo, BMSC-EVs reduced cell infiltration, reduced fibrotic tissue in the shoulder capsule, and improved shoulder mobility. In addition, via exosomal small RNA sequencing and qPCR analysis, let-7a-5p was verified to be the highest expressed miRNA with predicted antifibrotic capability in BMSC-EVs. The antifibrotic capacity of BMSC-EVs was significantly impaired after the knockdown of let-7a-5p. Moreover, we discovered that the mRNA of TGFBR1 (the membrane receptor of transforming growth factor β) was the target of let-7a-5p. Together, these findings elucidated the antifibrotic role of BMSC-EVs in shoulder capsular fibrosis. This study clarifies a new approach using stem cell-derived EVs therapy as an alternative to cell therapy, which may clinically benefit patients with SS in the future. KeAi Publishing 2022-01-23 /pmc/articles/PMC8965035/ /pubmed/35386460 http://dx.doi.org/10.1016/j.bioactmat.2022.01.016 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Luo, Zhiwen
Sun, Yaying
Qi, Beijie
Lin, Jinrong
Chen, Yisheng
Xu, Yuzhen
Chen, Jiwu
Human bone marrow mesenchymal stem cell-derived extracellular vesicles inhibit shoulder stiffness via let-7a/Tgfbr1 axis
title Human bone marrow mesenchymal stem cell-derived extracellular vesicles inhibit shoulder stiffness via let-7a/Tgfbr1 axis
title_full Human bone marrow mesenchymal stem cell-derived extracellular vesicles inhibit shoulder stiffness via let-7a/Tgfbr1 axis
title_fullStr Human bone marrow mesenchymal stem cell-derived extracellular vesicles inhibit shoulder stiffness via let-7a/Tgfbr1 axis
title_full_unstemmed Human bone marrow mesenchymal stem cell-derived extracellular vesicles inhibit shoulder stiffness via let-7a/Tgfbr1 axis
title_short Human bone marrow mesenchymal stem cell-derived extracellular vesicles inhibit shoulder stiffness via let-7a/Tgfbr1 axis
title_sort human bone marrow mesenchymal stem cell-derived extracellular vesicles inhibit shoulder stiffness via let-7a/tgfbr1 axis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965035/
https://www.ncbi.nlm.nih.gov/pubmed/35386460
http://dx.doi.org/10.1016/j.bioactmat.2022.01.016
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