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Exosomes Secreted from CXCR4 Overexpressing Mesenchymal Stem Cells Promote Cardioprotection via Akt Signaling Pathway following Myocardial Infarction
Background and Objective. Exosomes secreted from mesenchymal stem cells (MSC) have demonstrated cardioprotective effects. This study examined the role of exosomes derived from MSC overexpressing CXCR4 for recovery of cardiac functions after myocardial infarction (MI). Methods. In vitro, exosomes fro...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436515/ https://www.ncbi.nlm.nih.gov/pubmed/26074976 http://dx.doi.org/10.1155/2015/659890 |
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author | Kang, Kai Ma, Ruilian Cai, Wenfeng Huang, Wei Paul, Christian Liang, Jialiang Wang, Yuhua Zhao, Tiejun Kim, Ha Won Xu, Meifeng Millard, Ronald W. Wen, Zhili Wang, Yigang |
author_facet | Kang, Kai Ma, Ruilian Cai, Wenfeng Huang, Wei Paul, Christian Liang, Jialiang Wang, Yuhua Zhao, Tiejun Kim, Ha Won Xu, Meifeng Millard, Ronald W. Wen, Zhili Wang, Yigang |
author_sort | Kang, Kai |
collection | PubMed |
description | Background and Objective. Exosomes secreted from mesenchymal stem cells (MSC) have demonstrated cardioprotective effects. This study examined the role of exosomes derived from MSC overexpressing CXCR4 for recovery of cardiac functions after myocardial infarction (MI). Methods. In vitro, exosomes from MSC transduced with lentiviral CXCR4 (Exo(CR4)) encoding a silencing sequence or null vector were isolated and characterized by transmission electron microscopy and dynamic light scattering. Gene expression was then analyzed by qPCR and Western blotting. Cytoprotective effects on cardiomyocytes were evaluated and effects of exosomes on angiogenesis analyzed. In vivo, an exosome-pretreated MSC-sheet was implanted into a region of scarred myocardium in a rat MI model. Angiogenesis, infarct size, and cardiac functions were then analyzed. Results. In vitro, Exo(CR4) significantly upregulated IGF-1α and pAkt levels and downregulated active caspase 3 level in cardiomyocytes. Exo(CR4) also enhanced VEGF expression and vessel formation. However, effects of Exo(CR4) were abolished by an Akt inhibitor or CXCR4 knockdown. In vivo, Exo(CR4) treated MSC-sheet implantation promoted cardiac functional restoration by increasing angiogenesis, reducing infarct size, and improving cardiac remodeling. Conclusions. This study reveals a novel role of exosomes derived from MSC(CR4) and highlights a new mechanism of intercellular mediation of stem cells for MI treatment. |
format | Online Article Text |
id | pubmed-4436515 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-44365152015-06-14 Exosomes Secreted from CXCR4 Overexpressing Mesenchymal Stem Cells Promote Cardioprotection via Akt Signaling Pathway following Myocardial Infarction Kang, Kai Ma, Ruilian Cai, Wenfeng Huang, Wei Paul, Christian Liang, Jialiang Wang, Yuhua Zhao, Tiejun Kim, Ha Won Xu, Meifeng Millard, Ronald W. Wen, Zhili Wang, Yigang Stem Cells Int Research Article Background and Objective. Exosomes secreted from mesenchymal stem cells (MSC) have demonstrated cardioprotective effects. This study examined the role of exosomes derived from MSC overexpressing CXCR4 for recovery of cardiac functions after myocardial infarction (MI). Methods. In vitro, exosomes from MSC transduced with lentiviral CXCR4 (Exo(CR4)) encoding a silencing sequence or null vector were isolated and characterized by transmission electron microscopy and dynamic light scattering. Gene expression was then analyzed by qPCR and Western blotting. Cytoprotective effects on cardiomyocytes were evaluated and effects of exosomes on angiogenesis analyzed. In vivo, an exosome-pretreated MSC-sheet was implanted into a region of scarred myocardium in a rat MI model. Angiogenesis, infarct size, and cardiac functions were then analyzed. Results. In vitro, Exo(CR4) significantly upregulated IGF-1α and pAkt levels and downregulated active caspase 3 level in cardiomyocytes. Exo(CR4) also enhanced VEGF expression and vessel formation. However, effects of Exo(CR4) were abolished by an Akt inhibitor or CXCR4 knockdown. In vivo, Exo(CR4) treated MSC-sheet implantation promoted cardiac functional restoration by increasing angiogenesis, reducing infarct size, and improving cardiac remodeling. Conclusions. This study reveals a novel role of exosomes derived from MSC(CR4) and highlights a new mechanism of intercellular mediation of stem cells for MI treatment. Hindawi Publishing Corporation 2015 2015-05-05 /pmc/articles/PMC4436515/ /pubmed/26074976 http://dx.doi.org/10.1155/2015/659890 Text en Copyright © 2015 Kai Kang et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Kang, Kai Ma, Ruilian Cai, Wenfeng Huang, Wei Paul, Christian Liang, Jialiang Wang, Yuhua Zhao, Tiejun Kim, Ha Won Xu, Meifeng Millard, Ronald W. Wen, Zhili Wang, Yigang Exosomes Secreted from CXCR4 Overexpressing Mesenchymal Stem Cells Promote Cardioprotection via Akt Signaling Pathway following Myocardial Infarction |
title | Exosomes Secreted from CXCR4 Overexpressing Mesenchymal Stem Cells Promote Cardioprotection via Akt Signaling Pathway following Myocardial Infarction |
title_full | Exosomes Secreted from CXCR4 Overexpressing Mesenchymal Stem Cells Promote Cardioprotection via Akt Signaling Pathway following Myocardial Infarction |
title_fullStr | Exosomes Secreted from CXCR4 Overexpressing Mesenchymal Stem Cells Promote Cardioprotection via Akt Signaling Pathway following Myocardial Infarction |
title_full_unstemmed | Exosomes Secreted from CXCR4 Overexpressing Mesenchymal Stem Cells Promote Cardioprotection via Akt Signaling Pathway following Myocardial Infarction |
title_short | Exosomes Secreted from CXCR4 Overexpressing Mesenchymal Stem Cells Promote Cardioprotection via Akt Signaling Pathway following Myocardial Infarction |
title_sort | exosomes secreted from cxcr4 overexpressing mesenchymal stem cells promote cardioprotection via akt signaling pathway following myocardial infarction |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436515/ https://www.ncbi.nlm.nih.gov/pubmed/26074976 http://dx.doi.org/10.1155/2015/659890 |
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