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Human Adipose Mesenchymal Stem Cell-derived Exosomes Protect Mice from DSS-Induced Inflammatory Bowel Disease by Promoting Intestinal-stem-cell and Epithelial Regeneration

Inflammatory bowel disease (IBD) remains a severe disease for most patients, with its incidence and prevalence increasingly globally. Currently, there is no effective treatments for IBD, and traditional treatments have multiple side effects. Therefore, novel therapeutic strategies or alternative dru...

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Autores principales: Yu, Hongliang, Yang, Xudong, Xiao, Xian, Xu, Meiqian, Yang, Yanlei, Xue, Chunling, Li, Xuechun, Wang, Shihua, Zhao, Robert Chunhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: JKL International LLC 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407880/
https://www.ncbi.nlm.nih.gov/pubmed/34527419
http://dx.doi.org/10.14336/AD.2021.0601
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author Yu, Hongliang
Yang, Xudong
Xiao, Xian
Xu, Meiqian
Yang, Yanlei
Xue, Chunling
Li, Xuechun
Wang, Shihua
Zhao, Robert Chunhua
author_facet Yu, Hongliang
Yang, Xudong
Xiao, Xian
Xu, Meiqian
Yang, Yanlei
Xue, Chunling
Li, Xuechun
Wang, Shihua
Zhao, Robert Chunhua
author_sort Yu, Hongliang
collection PubMed
description Inflammatory bowel disease (IBD) remains a severe disease for most patients, with its incidence and prevalence increasingly globally. Currently, there is no effective treatments for IBD, and traditional treatments have multiple side effects. Therefore, novel therapeutic strategies or alternative drugs are urgently needed. Previous studies have shown that mesenchymal stem cell-derived exosomes have exhibited promising therapeutic effects on inflammatory disease. Here, we performed intravenous injection of human adipose mesenchymal stem cell (hADSC)-derived exosomes (hADSC-Exo) in a DSS-induced IBD mouse model and found that hADSC-Exo promoted functional recovery, downregulated inflammatory responses, reduced intestine cell apoptosis, increased epithelial regeneration and maintained intestinal barrier integrity. Moreover, we established a colon organoid, hADSC-Exo and TNF-α co-cultured system to explore the protective effect of hADSC-Exo on integrity of intestine mucosa and epithelial regeneration. We showed that hADSC-Exo not only can promote the proliferation and regeneration of Lgr5(+) ISCs and epithelial cells but also ameliorate the inflammation damage in TNF-α induced inflammatory damaged mice colon organoids. Taken together, our findings indicate that hADSC-Exo protects intestine integrity, activates intestine epithelial cell and ISCs proliferation, suggesting that hADSC-Exo might be a potential effective treatment approach for IBD. We also provide a theoretical basis for new therapeutic strategies for cell-free therapy in inflammatory bowel disease.
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spelling pubmed-84078802021-09-14 Human Adipose Mesenchymal Stem Cell-derived Exosomes Protect Mice from DSS-Induced Inflammatory Bowel Disease by Promoting Intestinal-stem-cell and Epithelial Regeneration Yu, Hongliang Yang, Xudong Xiao, Xian Xu, Meiqian Yang, Yanlei Xue, Chunling Li, Xuechun Wang, Shihua Zhao, Robert Chunhua Aging Dis Orginal Article Inflammatory bowel disease (IBD) remains a severe disease for most patients, with its incidence and prevalence increasingly globally. Currently, there is no effective treatments for IBD, and traditional treatments have multiple side effects. Therefore, novel therapeutic strategies or alternative drugs are urgently needed. Previous studies have shown that mesenchymal stem cell-derived exosomes have exhibited promising therapeutic effects on inflammatory disease. Here, we performed intravenous injection of human adipose mesenchymal stem cell (hADSC)-derived exosomes (hADSC-Exo) in a DSS-induced IBD mouse model and found that hADSC-Exo promoted functional recovery, downregulated inflammatory responses, reduced intestine cell apoptosis, increased epithelial regeneration and maintained intestinal barrier integrity. Moreover, we established a colon organoid, hADSC-Exo and TNF-α co-cultured system to explore the protective effect of hADSC-Exo on integrity of intestine mucosa and epithelial regeneration. We showed that hADSC-Exo not only can promote the proliferation and regeneration of Lgr5(+) ISCs and epithelial cells but also ameliorate the inflammation damage in TNF-α induced inflammatory damaged mice colon organoids. Taken together, our findings indicate that hADSC-Exo protects intestine integrity, activates intestine epithelial cell and ISCs proliferation, suggesting that hADSC-Exo might be a potential effective treatment approach for IBD. We also provide a theoretical basis for new therapeutic strategies for cell-free therapy in inflammatory bowel disease. JKL International LLC 2021-09-01 /pmc/articles/PMC8407880/ /pubmed/34527419 http://dx.doi.org/10.14336/AD.2021.0601 Text en Copyright: © 2021 Yu et al. https://creativecommons.org/licenses/by/2.0/this is an open access article distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Orginal Article
Yu, Hongliang
Yang, Xudong
Xiao, Xian
Xu, Meiqian
Yang, Yanlei
Xue, Chunling
Li, Xuechun
Wang, Shihua
Zhao, Robert Chunhua
Human Adipose Mesenchymal Stem Cell-derived Exosomes Protect Mice from DSS-Induced Inflammatory Bowel Disease by Promoting Intestinal-stem-cell and Epithelial Regeneration
title Human Adipose Mesenchymal Stem Cell-derived Exosomes Protect Mice from DSS-Induced Inflammatory Bowel Disease by Promoting Intestinal-stem-cell and Epithelial Regeneration
title_full Human Adipose Mesenchymal Stem Cell-derived Exosomes Protect Mice from DSS-Induced Inflammatory Bowel Disease by Promoting Intestinal-stem-cell and Epithelial Regeneration
title_fullStr Human Adipose Mesenchymal Stem Cell-derived Exosomes Protect Mice from DSS-Induced Inflammatory Bowel Disease by Promoting Intestinal-stem-cell and Epithelial Regeneration
title_full_unstemmed Human Adipose Mesenchymal Stem Cell-derived Exosomes Protect Mice from DSS-Induced Inflammatory Bowel Disease by Promoting Intestinal-stem-cell and Epithelial Regeneration
title_short Human Adipose Mesenchymal Stem Cell-derived Exosomes Protect Mice from DSS-Induced Inflammatory Bowel Disease by Promoting Intestinal-stem-cell and Epithelial Regeneration
title_sort human adipose mesenchymal stem cell-derived exosomes protect mice from dss-induced inflammatory bowel disease by promoting intestinal-stem-cell and epithelial regeneration
topic Orginal Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407880/
https://www.ncbi.nlm.nih.gov/pubmed/34527419
http://dx.doi.org/10.14336/AD.2021.0601
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