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Cited by 360Extracellular vesicles in diseaseMesenchymal stem cell researchMicroRNA in disease regulation

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

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Ferguson, Scott W., Wang, Jinli, Lee, Christine J., Liu, Maixian, Neelamegham, Sriram, Canty, John M., Nguyen, Juliane·2018·Scientific Reports
DOI 10.1038/s41598-018-19581-xPMC PMC5780426
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Abstract

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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Cited by

Sorted by citations

Authors
Ferguson, S. W., Wang, J., Lee, C. J., Liu, M., Neelamegham, S., Canty, J. M., & Nguyen, J.
Affiliations
  • University at Buffalo, State University of New York (US)
  • VA Western New York Healthcare System (US)
Corresponding author
Nguyen, Juliane
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2018-01-23
Volume
8
Issue
1
Pages
1419-1419
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-018-19581-x
PMC
PMC5780426
OpenAlex
W2796324227
Cited by
360
References
1
Citations by year
2026: 13 · 2025: 34 · 2024: 37 · 2023: 42 · 2022: 53 · 2021: 72 · 2020: 58 · 2019: 38 · 2018: 13
FWCI
16.10
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • U.S. Department of Veterans Affairs (1IO1BX002659, UL1TR001412, I01 BX002659)
  • National Institutes of Health (1IO1BX002659, UL1TR001412, EB023262, EB021454, HL103411)
  • National Heart, Lung, and Blood Institute (R01HL061610, R21HL126082, R01HL103411)
  • National Institute of Biomedical Imaging and Bioengineering (R21EB021454, R01EB023262)
  • National Center for Advancing Translational Sciences (1IO1BX002659)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
Keywords
mesenchymal stem cell-derived exosomes, microRNA, angiogenesis, myocardial fibrosis, cardiomyocyte apoptosis, cardiomyocyte proliferation, Wnt signaling, TGF-beta signaling, PDGF signaling, collagen synthesis
MeSH terms
Cells, Cultured, Collagen, Fibroblasts, Gene Expression Regulation, Humans, Apoptosis, Neovascularization, Physiologic, Myocytes, Cardiac, MicroRNAs, Cell Proliferation, Gene Regulatory Networks, Exosomes, Mesenchymal Stem Cells, Human Umbilical Vein Endothelial Cells

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