Evidence map›Paper›PMID 29362496›Full record

ArticleScientific reports2018

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

Scott W Ferguson, Jinli Wang, Christine J Lee, Maixian Liu, Sriram Neelamegham, John M Canty, Juliane Nguyen

Abstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 246 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
246citing papers in PubMed, 3 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

246 citing papers in PubMed, 3 syntheses or guidelines pooled it.

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186 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Scott W FergusonDepartment of Pharmaceutical Sciences, School of Pharmacy, University at Buffalo, The State University of New York, Buffalo, NY, 14214, USA.
Jinli WangDepartment of Pharmaceutical Sciences, School of Pharmacy, University at Buffalo, The State University of New York, Buffalo, NY, 14214, USA.
Christine J LeeDepartment of Pharmaceutical Sciences, School of Pharmacy, University at Buffalo, The State University of New York, Buffalo, NY, 14214, USA.
Maixian LiuDepartment of Pharmaceutical Sciences, School of Pharmacy, University at Buffalo, The State University of New York, Buffalo, NY, 14214, USA.
Sriram NeelameghamDepartment of Chemical and Biological Engineering, Department of Biomedical Engineering, Clinical and Translational Research Center of the University at Buffalo, The State University of New York, Buffalo, NY, 14260, USA.
John M CantyDepartment of Medicine, Department of Physiology and Biophysics, Department of Biomedical Engineering, The Clinical and Translational Research Center of the University at Buffalo, Buffalo, New York and the VA Western New York Healthcare System, Buffalo, NY, 14214, USA.
Juliane NguyenDepartment of Pharmaceutical Sciences, School of Pharmacy, University at Buffalo, The State University of New York, Buffalo, NY, 14214, USA. julianen@buffalo.edu.ORCID http://orcid.org/0000-0002-8578-7396

Funding

University of Buffalo Clinical and Translational Science Institute - Supplement SchulyerUL1TR001412 · NCATS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI MURPHY, TIMOTHY F · 2015 to 2024
$33.8M
Systems Biology of GlycosylationR01HL103411 · NHLBI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI NEELAMEGHAM, SRIRAM · 2011 to 2025
$7.1M
Metabolic Adaptation and Functional Recovery of Hibernating MyocardiumR01HL061610 · NHLBI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI CANTY, JOHN M · 2000 to 2018
$6.0M
RNA EXO-Codes: A novel way to reprogram pathological exosomesR01EB023262 · NIBIB · UNIV OF NORTH CAROLINA CHAPEL HILL · PI NGUYEN, JULIANE · 2017 to 2020
$1.7M
Self-replicating RNA-nanoplexes for programming monocytes to regenerate the heartR21HL126082 · NHLBI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI NGUYEN, JULIANE · 2015 to 2016
$432k
Maximizing small RNA delivery with signaling pepitdesR21EB021454 · NIBIB · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI NGUYEN, JULIANE · 2015 to 2016
$432k
Preventing and Reversing Interstitial Fibrosis in HFpEFI01BX002659 · VA · VA WESTERN NEW YORK HEALTHCARE SYSTEM · PI Brian Raymond Weil · 2016 to 2026
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BLRD VA I01 BX002659NCATS NIH HHS UL1 TR001412NHLBI NIH HHS R01 HL061610NHLBI NIH HHS R01 HL103411NHLBI NIH HHS R21 HL126082NIBIB NIH HHS R01 EB023262NIBIB NIH HHS R21 EB021454
6 · The paper itself

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.

Indexed as

Gene Regulatory NetworksApoptosisCell ProliferationCells, CulturedCollagenExosomesFibroblastsGene Expression RegulationHumansHuman Umbilical Vein Endothelial CellsMesenchymal Stem CellsMicroRNAsMyocytes, CardiacNeovascularization, PhysiologicCollagenMicroRNAs

Identifiers

PMID29362496
PMCPMC5780426

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.