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The microRNA regulatory landscape of MSC-derived exosomes: a systems view

Mesenchymal stem cell (MSC)-derived exosomes mediate tissue regeneration in a variety of diseases including ischemic heart injury, liver fibrosis, and cerebrovascular disease. Despite an increasing number of studies reporting the therapeutic effects of MSC exosomes, the underlying molecular mechanis...

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Autores principales: Ferguson, Scott W., Wang, Jinli, Lee, Christine J., Liu, Maixian, Neelamegham, Sriram, Canty, John M., Nguyen, Juliane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5780426/
https://www.ncbi.nlm.nih.gov/pubmed/29362496
http://dx.doi.org/10.1038/s41598-018-19581-x
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author Ferguson, Scott W.
Wang, Jinli
Lee, Christine J.
Liu, Maixian
Neelamegham, Sriram
Canty, John M.
Nguyen, Juliane
author_facet Ferguson, Scott W.
Wang, Jinli
Lee, Christine J.
Liu, Maixian
Neelamegham, Sriram
Canty, John M.
Nguyen, Juliane
author_sort Ferguson, Scott W.
collection PubMed
description Mesenchymal stem cell (MSC)-derived exosomes mediate tissue regeneration in a variety of diseases including ischemic heart injury, liver fibrosis, and cerebrovascular disease. Despite an increasing number of studies reporting the therapeutic effects of MSC exosomes, the underlying molecular mechanisms and their miRNA complement are poorly characterized. Here we microRNA (miRNA)-profiled MSC exosomes and conducted a network analysis to identify the dominant biological processes and pathways modulated by exosomal miRNAs. At a system level, miRNA-targeted genes were enriched for (cardio)vascular and angiogenesis processes in line with observed cardiovascular regenerative effects. Targeted pathways were related to Wnt signaling, pro-fibrotic signaling via TGF-β and PDGF, proliferation, and apoptosis. When tested, MSC exosomes reduced collagen production by cardiac fibroblasts, protected cardiomyocytes from apoptosis, and increased angiogenesis in HUVECs. The intrinsic beneficial effects were further improved by virus-free enrichment of MSC exosomes with network-informed regenerative miRNAs capable of promoting angiogenesis and cardiomyocyte proliferation. The data presented here help define the miRNA landscape of MSC exosomes, establish their biological functions through network analyses at a system level, and provide a platform for modulating the overall phenotypic effects of exosomes.
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spelling pubmed-57804262018-02-06 The microRNA regulatory landscape of MSC-derived exosomes: a systems view Ferguson, Scott W. Wang, Jinli Lee, Christine J. Liu, Maixian Neelamegham, Sriram Canty, John M. Nguyen, Juliane Sci Rep Article Mesenchymal stem cell (MSC)-derived exosomes mediate tissue regeneration in a variety of diseases including ischemic heart injury, liver fibrosis, and cerebrovascular disease. Despite an increasing number of studies reporting the therapeutic effects of MSC exosomes, the underlying molecular mechanisms and their miRNA complement are poorly characterized. Here we microRNA (miRNA)-profiled MSC exosomes and conducted a network analysis to identify the dominant biological processes and pathways modulated by exosomal miRNAs. At a system level, miRNA-targeted genes were enriched for (cardio)vascular and angiogenesis processes in line with observed cardiovascular regenerative effects. Targeted pathways were related to Wnt signaling, pro-fibrotic signaling via TGF-β and PDGF, proliferation, and apoptosis. When tested, MSC exosomes reduced collagen production by cardiac fibroblasts, protected cardiomyocytes from apoptosis, and increased angiogenesis in HUVECs. The intrinsic beneficial effects were further improved by virus-free enrichment of MSC exosomes with network-informed regenerative miRNAs capable of promoting angiogenesis and cardiomyocyte proliferation. The data presented here help define the miRNA landscape of MSC exosomes, establish their biological functions through network analyses at a system level, and provide a platform for modulating the overall phenotypic effects of exosomes. Nature Publishing Group UK 2018-01-23 /pmc/articles/PMC5780426/ /pubmed/29362496 http://dx.doi.org/10.1038/s41598-018-19581-x Text en © The Author(s) 2018 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Ferguson, Scott W.
Wang, Jinli
Lee, Christine J.
Liu, Maixian
Neelamegham, Sriram
Canty, John M.
Nguyen, Juliane
The microRNA regulatory landscape of MSC-derived exosomes: a systems view
title The microRNA regulatory landscape of MSC-derived exosomes: a systems view
title_full The microRNA regulatory landscape of MSC-derived exosomes: a systems view
title_fullStr The microRNA regulatory landscape of MSC-derived exosomes: a systems view
title_full_unstemmed The microRNA regulatory landscape of MSC-derived exosomes: a systems view
title_short The microRNA regulatory landscape of MSC-derived exosomes: a systems view
title_sort microrna regulatory landscape of msc-derived exosomes: a systems view
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5780426/
https://www.ncbi.nlm.nih.gov/pubmed/29362496
http://dx.doi.org/10.1038/s41598-018-19581-x
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