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Bone marrow-derived mesenchymal stem cells attenuate myocardial ischemia–reperfusion injury via upregulation of splenic regulatory T cells
BACKGROUND: Myocardial ischemia–reperfusion injury (MIRI) is the main pathological manifestation of cardiovascular diseases such as myocardial infarction. The potential therapeutic effects of bone marrow-derived mesenchymal stem cells (BM-MSCs) and the participation of regulatory T cells (Tregs) in...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080373/ https://www.ncbi.nlm.nih.gov/pubmed/33906602 http://dx.doi.org/10.1186/s12872-021-02007-4 |
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author | Pang, Ling-Xiao Cai, Wen-Wei Li, Qian Li, Heng-Jie Fei, Min Yuan, Yong-Sheng Sheng, Bin Zhang, Ke An, Rong-Cheng Ou, Ying-Wei Zeng, Wen-Jie |
author_facet | Pang, Ling-Xiao Cai, Wen-Wei Li, Qian Li, Heng-Jie Fei, Min Yuan, Yong-Sheng Sheng, Bin Zhang, Ke An, Rong-Cheng Ou, Ying-Wei Zeng, Wen-Jie |
author_sort | Pang, Ling-Xiao |
collection | PubMed |
description | BACKGROUND: Myocardial ischemia–reperfusion injury (MIRI) is the main pathological manifestation of cardiovascular diseases such as myocardial infarction. The potential therapeutic effects of bone marrow-derived mesenchymal stem cells (BM-MSCs) and the participation of regulatory T cells (Tregs) in MIRI remains to be defined. METHODS: We used the experimental acute MIRI that was induced in mice by left ascending coronary ischemia, which were subsequently randomized to receive immunoglobulin G (IgG) or anti-CD25 antibody PC61 with or without intravenously injected BM-MSCs. The splenectomized mice underwent prior to experimental MIRI followed by intravenous administration of BM-MSCs. At 72 h post-MIRI, the hearts and spleens were harvested and subjected to cytometric and histologic analyses. RESULTS: CD25(+)Foxp3(+) regulatory T cells were significantly elevated after MIRI in the hearts and spleens of mice receiving IgG + BM-MSCs and PC61 + BM-MSCs compared to the respective control mice (all p < 0.01). This was accompanied by upregulation of interleukin 10 and transforming growth factor β1 and downregulation of creatinine kinase and lactate dehydrogenase in the serum. The post-MIRI mice receiving BM-MSCs showed attenuated inflammation and cellular apoptosis in the heart. Meanwhile, splenectomy compromised all therapeutic effects of BM-MSCs. CONCLUSION: Administration of BM-MSCs effectively alleviates MIRI in mice through inducing Treg activation, particularly in the spleen. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12872-021-02007-4. |
format | Online Article Text |
id | pubmed-8080373 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-80803732021-04-29 Bone marrow-derived mesenchymal stem cells attenuate myocardial ischemia–reperfusion injury via upregulation of splenic regulatory T cells Pang, Ling-Xiao Cai, Wen-Wei Li, Qian Li, Heng-Jie Fei, Min Yuan, Yong-Sheng Sheng, Bin Zhang, Ke An, Rong-Cheng Ou, Ying-Wei Zeng, Wen-Jie BMC Cardiovasc Disord Research BACKGROUND: Myocardial ischemia–reperfusion injury (MIRI) is the main pathological manifestation of cardiovascular diseases such as myocardial infarction. The potential therapeutic effects of bone marrow-derived mesenchymal stem cells (BM-MSCs) and the participation of regulatory T cells (Tregs) in MIRI remains to be defined. METHODS: We used the experimental acute MIRI that was induced in mice by left ascending coronary ischemia, which were subsequently randomized to receive immunoglobulin G (IgG) or anti-CD25 antibody PC61 with or without intravenously injected BM-MSCs. The splenectomized mice underwent prior to experimental MIRI followed by intravenous administration of BM-MSCs. At 72 h post-MIRI, the hearts and spleens were harvested and subjected to cytometric and histologic analyses. RESULTS: CD25(+)Foxp3(+) regulatory T cells were significantly elevated after MIRI in the hearts and spleens of mice receiving IgG + BM-MSCs and PC61 + BM-MSCs compared to the respective control mice (all p < 0.01). This was accompanied by upregulation of interleukin 10 and transforming growth factor β1 and downregulation of creatinine kinase and lactate dehydrogenase in the serum. The post-MIRI mice receiving BM-MSCs showed attenuated inflammation and cellular apoptosis in the heart. Meanwhile, splenectomy compromised all therapeutic effects of BM-MSCs. CONCLUSION: Administration of BM-MSCs effectively alleviates MIRI in mice through inducing Treg activation, particularly in the spleen. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12872-021-02007-4. BioMed Central 2021-04-27 /pmc/articles/PMC8080373/ /pubmed/33906602 http://dx.doi.org/10.1186/s12872-021-02007-4 Text en © The Author(s) 2021 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 Pang, Ling-Xiao Cai, Wen-Wei Li, Qian Li, Heng-Jie Fei, Min Yuan, Yong-Sheng Sheng, Bin Zhang, Ke An, Rong-Cheng Ou, Ying-Wei Zeng, Wen-Jie Bone marrow-derived mesenchymal stem cells attenuate myocardial ischemia–reperfusion injury via upregulation of splenic regulatory T cells |
title | Bone marrow-derived mesenchymal stem cells attenuate myocardial ischemia–reperfusion injury via upregulation of splenic regulatory T cells |
title_full | Bone marrow-derived mesenchymal stem cells attenuate myocardial ischemia–reperfusion injury via upregulation of splenic regulatory T cells |
title_fullStr | Bone marrow-derived mesenchymal stem cells attenuate myocardial ischemia–reperfusion injury via upregulation of splenic regulatory T cells |
title_full_unstemmed | Bone marrow-derived mesenchymal stem cells attenuate myocardial ischemia–reperfusion injury via upregulation of splenic regulatory T cells |
title_short | Bone marrow-derived mesenchymal stem cells attenuate myocardial ischemia–reperfusion injury via upregulation of splenic regulatory T cells |
title_sort | bone marrow-derived mesenchymal stem cells attenuate myocardial ischemia–reperfusion injury via upregulation of splenic regulatory t cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080373/ https://www.ncbi.nlm.nih.gov/pubmed/33906602 http://dx.doi.org/10.1186/s12872-021-02007-4 |
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