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Perinatal tissue-derived exosomes ameliorate colitis in mice by regulating the Foxp3 + Treg cells and gut microbiota

BACKGROUND: The capacity of self-renewal and multipotent differentiation makes mesenchymal stem cells (MSC) one of the most widely investigated cell lines in preclinical studies as cell-based therapies. However, the low survival rate and poor homing efficiency of MSCs after transplantation hinder th...

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Autores principales: Yan, Yaping, Li, Kaixiu, Jiang, Jiang, Jiang, Lihong, Ma, Xiang, Ai, Fang, Qiu, Shuai, Si, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10029206/
https://www.ncbi.nlm.nih.gov/pubmed/36941715
http://dx.doi.org/10.1186/s13287-023-03263-1
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author Yan, Yaping
Li, Kaixiu
Jiang, Jiang
Jiang, Lihong
Ma, Xiang
Ai, Fang
Qiu, Shuai
Si, Wei
author_facet Yan, Yaping
Li, Kaixiu
Jiang, Jiang
Jiang, Lihong
Ma, Xiang
Ai, Fang
Qiu, Shuai
Si, Wei
author_sort Yan, Yaping
collection PubMed
description BACKGROUND: The capacity of self-renewal and multipotent differentiation makes mesenchymal stem cells (MSC) one of the most widely investigated cell lines in preclinical studies as cell-based therapies. However, the low survival rate and poor homing efficiency of MSCs after transplantation hinder the therapeutic application. Exosomes derived from MSCs have shown promising therapeutic potential in many diseases. However, the heterogeneity of MSCs may lead to differences in the function of secreting exosomes. In this study, the therapeutic effects of hUC-Exos and hFP-Exos on the DSS-induced colitis mouse model were investigated. METHODS: The colitis mouse models were randomly divided into four groups: (1) DSS administered for 7 days and euthanasia (DSS7D), (2) DSS administered for 7 days and kept for another 7 days without any treatment (DSS14D), (3) DSS administered for 7 days and followed with hUC-EVs infusion for 7 days (hUC-EVs) and (4) DSS administered for 7 days and followed with hFP-EVs infusion for 7 days (hFP-EVs). We analyzed colon length, histopathology, Treg cells, cytokines and gut microbiota composition in each group. RESULTS: A large amount of IL-6, IL-17 and IFN-γ were produced along with the decrease in the number of CD4 + Foxp3 + and CD8 + Foxp3 + cells in DSS7D group, which indicated that Th17 cells were activated and Treg cells were suppressed. We found that the number of CD4 + Foxp3 + and CD8 + Foxp3 + cells increased in order to suppress inflammation, but the length of colon did not recover and the symotoms were worsened of the colonic tissue in DSS14D group. The subsequent infusion of either hUC-Exos or hFP-Exos mediated the transformation of Treg and Th17 cells in colitis mice to maintain immune balance. The infusion of hUC-Exos and hFP-Exos also both reduced the abundance of pro-inflammatory intestinal bacterial such as Verrucomicrobia and Akkermansia muciniphila to improve colitis. CONCLUSIONS: We found that Foxp3 + Treg cells can inhibit the inflammatory response, and the over-activated Treg cells can still further damage the intestinal mucosa. hUC-Exos and hFP-Exos can control inflammation by regulating the balance between Th17 cells and Treg cells. Decreased inflammatory response improved the structure of colon wall in mice and reduced the abundance of pro-inflammatory bacteria in the intestine. The improvement of intestinal wall structure provides conditions for the reproduction of beneficial bacteria, which further contributes to the reduction of colitis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-023-03263-1.
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spelling pubmed-100292062023-03-22 Perinatal tissue-derived exosomes ameliorate colitis in mice by regulating the Foxp3 + Treg cells and gut microbiota Yan, Yaping Li, Kaixiu Jiang, Jiang Jiang, Lihong Ma, Xiang Ai, Fang Qiu, Shuai Si, Wei Stem Cell Res Ther Research BACKGROUND: The capacity of self-renewal and multipotent differentiation makes mesenchymal stem cells (MSC) one of the most widely investigated cell lines in preclinical studies as cell-based therapies. However, the low survival rate and poor homing efficiency of MSCs after transplantation hinder the therapeutic application. Exosomes derived from MSCs have shown promising therapeutic potential in many diseases. However, the heterogeneity of MSCs may lead to differences in the function of secreting exosomes. In this study, the therapeutic effects of hUC-Exos and hFP-Exos on the DSS-induced colitis mouse model were investigated. METHODS: The colitis mouse models were randomly divided into four groups: (1) DSS administered for 7 days and euthanasia (DSS7D), (2) DSS administered for 7 days and kept for another 7 days without any treatment (DSS14D), (3) DSS administered for 7 days and followed with hUC-EVs infusion for 7 days (hUC-EVs) and (4) DSS administered for 7 days and followed with hFP-EVs infusion for 7 days (hFP-EVs). We analyzed colon length, histopathology, Treg cells, cytokines and gut microbiota composition in each group. RESULTS: A large amount of IL-6, IL-17 and IFN-γ were produced along with the decrease in the number of CD4 + Foxp3 + and CD8 + Foxp3 + cells in DSS7D group, which indicated that Th17 cells were activated and Treg cells were suppressed. We found that the number of CD4 + Foxp3 + and CD8 + Foxp3 + cells increased in order to suppress inflammation, but the length of colon did not recover and the symotoms were worsened of the colonic tissue in DSS14D group. The subsequent infusion of either hUC-Exos or hFP-Exos mediated the transformation of Treg and Th17 cells in colitis mice to maintain immune balance. The infusion of hUC-Exos and hFP-Exos also both reduced the abundance of pro-inflammatory intestinal bacterial such as Verrucomicrobia and Akkermansia muciniphila to improve colitis. CONCLUSIONS: We found that Foxp3 + Treg cells can inhibit the inflammatory response, and the over-activated Treg cells can still further damage the intestinal mucosa. hUC-Exos and hFP-Exos can control inflammation by regulating the balance between Th17 cells and Treg cells. Decreased inflammatory response improved the structure of colon wall in mice and reduced the abundance of pro-inflammatory bacteria in the intestine. The improvement of intestinal wall structure provides conditions for the reproduction of beneficial bacteria, which further contributes to the reduction of colitis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-023-03263-1. BioMed Central 2023-03-20 /pmc/articles/PMC10029206/ /pubmed/36941715 http://dx.doi.org/10.1186/s13287-023-03263-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Yan, Yaping
Li, Kaixiu
Jiang, Jiang
Jiang, Lihong
Ma, Xiang
Ai, Fang
Qiu, Shuai
Si, Wei
Perinatal tissue-derived exosomes ameliorate colitis in mice by regulating the Foxp3 + Treg cells and gut microbiota
title Perinatal tissue-derived exosomes ameliorate colitis in mice by regulating the Foxp3 + Treg cells and gut microbiota
title_full Perinatal tissue-derived exosomes ameliorate colitis in mice by regulating the Foxp3 + Treg cells and gut microbiota
title_fullStr Perinatal tissue-derived exosomes ameliorate colitis in mice by regulating the Foxp3 + Treg cells and gut microbiota
title_full_unstemmed Perinatal tissue-derived exosomes ameliorate colitis in mice by regulating the Foxp3 + Treg cells and gut microbiota
title_short Perinatal tissue-derived exosomes ameliorate colitis in mice by regulating the Foxp3 + Treg cells and gut microbiota
title_sort perinatal tissue-derived exosomes ameliorate colitis in mice by regulating the foxp3 + treg cells and gut microbiota
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10029206/
https://www.ncbi.nlm.nih.gov/pubmed/36941715
http://dx.doi.org/10.1186/s13287-023-03263-1
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