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Human ESC-sEVs alleviate age-related bone loss by rejuvenating senescent bone marrow-derived mesenchymal stem cells

Tissue-resident stem cell senescence leads to stem cell exhaustion, which is a major cause of physiological and pathological ageing. Stem cell-derived extracellular vesicles (SC-EVs) have been reported in preclinical studies to possess therapeutic potential for diverse diseases. However, whether SC-...

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Autores principales: Gong, Liangzhi, Chen, Bi, Zhang, Juntao, Sun, Yongjin, Yuan, Ji, Niu, Xin, Hu, Guowen, Chen, Yu, Xie, Zongping, Deng, Zhifeng, Li, Qing, Wang, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480439/
https://www.ncbi.nlm.nih.gov/pubmed/32944188
http://dx.doi.org/10.1080/20013078.2020.1800971
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author Gong, Liangzhi
Chen, Bi
Zhang, Juntao
Sun, Yongjin
Yuan, Ji
Niu, Xin
Hu, Guowen
Chen, Yu
Xie, Zongping
Deng, Zhifeng
Li, Qing
Wang, Yang
author_facet Gong, Liangzhi
Chen, Bi
Zhang, Juntao
Sun, Yongjin
Yuan, Ji
Niu, Xin
Hu, Guowen
Chen, Yu
Xie, Zongping
Deng, Zhifeng
Li, Qing
Wang, Yang
author_sort Gong, Liangzhi
collection PubMed
description Tissue-resident stem cell senescence leads to stem cell exhaustion, which is a major cause of physiological and pathological ageing. Stem cell-derived extracellular vesicles (SC-EVs) have been reported in preclinical studies to possess therapeutic potential for diverse diseases. However, whether SC-EVs can rejuvenate senescent tissue stem cells to prevent age-related disorders still remains unknown. Here, we show that chronic application of human embryonic stem cell-derived small extracellular vesicles (hESC-sEVs) rescues the function of senescent bone marrow mesenchymal stem cells (BM-MSCs) and prevents age-related bone loss in ageing mice. Transcriptome analysis revealed that hESC-sEVs treatment upregulated the expression of genes involved in antiaging, stem cell proliferation and osteogenic differentiation in BM-MSCs. Furthermore, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis identified 4122 proteins encapsulated in hESC-sEVs. Bioinformatics analysis predicted that the protein components in the hESCs-sEVs function in a synergistic way to induce the activation of several canonical signalling pathways, including Wnt, Sirtuin, AMPK, PTEN signalling, which results in the upregulation of antiaging genes in BM-MSCs and then the recovery of senescent BM-MSCs function. Collectively, our findings reveal the effect of hESC-sEVs in reversing BM-MSCs senescence and age-related osteogenic dysfunction, thereby preventing age-related bone loss. Because hESC-sEVs could alleviate senescence of tissue-resident stem cells, they might be promising therapeutic candidates for age-related diseases.
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spelling pubmed-74804392020-09-16 Human ESC-sEVs alleviate age-related bone loss by rejuvenating senescent bone marrow-derived mesenchymal stem cells Gong, Liangzhi Chen, Bi Zhang, Juntao Sun, Yongjin Yuan, Ji Niu, Xin Hu, Guowen Chen, Yu Xie, Zongping Deng, Zhifeng Li, Qing Wang, Yang J Extracell Vesicles Research Article Tissue-resident stem cell senescence leads to stem cell exhaustion, which is a major cause of physiological and pathological ageing. Stem cell-derived extracellular vesicles (SC-EVs) have been reported in preclinical studies to possess therapeutic potential for diverse diseases. However, whether SC-EVs can rejuvenate senescent tissue stem cells to prevent age-related disorders still remains unknown. Here, we show that chronic application of human embryonic stem cell-derived small extracellular vesicles (hESC-sEVs) rescues the function of senescent bone marrow mesenchymal stem cells (BM-MSCs) and prevents age-related bone loss in ageing mice. Transcriptome analysis revealed that hESC-sEVs treatment upregulated the expression of genes involved in antiaging, stem cell proliferation and osteogenic differentiation in BM-MSCs. Furthermore, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis identified 4122 proteins encapsulated in hESC-sEVs. Bioinformatics analysis predicted that the protein components in the hESCs-sEVs function in a synergistic way to induce the activation of several canonical signalling pathways, including Wnt, Sirtuin, AMPK, PTEN signalling, which results in the upregulation of antiaging genes in BM-MSCs and then the recovery of senescent BM-MSCs function. Collectively, our findings reveal the effect of hESC-sEVs in reversing BM-MSCs senescence and age-related osteogenic dysfunction, thereby preventing age-related bone loss. Because hESC-sEVs could alleviate senescence of tissue-resident stem cells, they might be promising therapeutic candidates for age-related diseases. Taylor & Francis 2020-08-10 /pmc/articles/PMC7480439/ /pubmed/32944188 http://dx.doi.org/10.1080/20013078.2020.1800971 Text en © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Gong, Liangzhi
Chen, Bi
Zhang, Juntao
Sun, Yongjin
Yuan, Ji
Niu, Xin
Hu, Guowen
Chen, Yu
Xie, Zongping
Deng, Zhifeng
Li, Qing
Wang, Yang
Human ESC-sEVs alleviate age-related bone loss by rejuvenating senescent bone marrow-derived mesenchymal stem cells
title Human ESC-sEVs alleviate age-related bone loss by rejuvenating senescent bone marrow-derived mesenchymal stem cells
title_full Human ESC-sEVs alleviate age-related bone loss by rejuvenating senescent bone marrow-derived mesenchymal stem cells
title_fullStr Human ESC-sEVs alleviate age-related bone loss by rejuvenating senescent bone marrow-derived mesenchymal stem cells
title_full_unstemmed Human ESC-sEVs alleviate age-related bone loss by rejuvenating senescent bone marrow-derived mesenchymal stem cells
title_short Human ESC-sEVs alleviate age-related bone loss by rejuvenating senescent bone marrow-derived mesenchymal stem cells
title_sort human esc-sevs alleviate age-related bone loss by rejuvenating senescent bone marrow-derived mesenchymal stem cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480439/
https://www.ncbi.nlm.nih.gov/pubmed/32944188
http://dx.doi.org/10.1080/20013078.2020.1800971
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