Evidence map›Paper›PMID 29273797›Full record

ArticleScientific reports2017

Thy-1 dependent uptake of mesenchymal stem cell-derived extracellular vesicles blocks myofibroblastic differentiation.

Tzu-Pin Shentu, Tse-Shun Huang, Mateja Cernelc-Kohan, Joy Chan, Simon S Wong, Celia R Espinoza, Chunting Tan, Irene Gramaglia, Henri van der Heyde, Shu Chien and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 1 pooled it
3.8field-weighted citation impact, top 6% of its field
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

63 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.

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  12. Metabolomic profiling of human bladder tissue extracts.Metabolomics : Official journal of the Metabolomic Society · 2024
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3 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

11 authors at 2 institutions in 1 country.

Tzu-Pin ShentuDepartment of Pediatrics, Division of Respiratory Medicine, University of California-San Diego, La Jolla, California, USA. tpshentu@gmail.com.
Tse-Shun HuangInstitute of Engineering in Medicine, University of California at San Diego, La Jolla, California, USA.
Mateja Cernelc-KohanDepartment of Pediatrics, Division of Respiratory Medicine, University of California-San Diego, La Jolla, California, USA.
Joy ChanUCLA Medical Center, Los Angeles, California, USA.
Simon S WongDepartment of Pediatrics, Division of Respiratory Medicine, University of California-San Diego, La Jolla, California, USA.
Celia R EspinozaDepartment of Pediatrics, Division of Respiratory Medicine, University of California-San Diego, La Jolla, California, USA.
Chunting TanDepartment of Pediatrics, Division of Respiratory Medicine, University of California-San Diego, La Jolla, California, USA.
Irene GramagliaLa Jolla Infectious Disease Institute, San Diego, California, USA.
Henri van der HeydeLa Jolla Infectious Disease Institute, San Diego, California, USA.
Shu ChienInstitute of Engineering in Medicine, University of California at San Diego, La Jolla, California, USA.
James S HagoodDepartment of Pediatrics, Division of Respiratory Medicine, University of California-San Diego, La Jolla, California, USA. jhagood@ucsd.edu.ORCID 0000-0003-3938-0330
University of California San Diego · USUCLA Medical Center · US

Funding

Targeting TGF-b Inhibitors and PPAR-y Agonists To Enhance IPF TherapyP01HL119165 · NHLBI · PROTEOGENOMICS RESEARCH INSTIT/SYS/ MED · PI BOROK, ZEA · 2015 to 2019
$13.6M
Alveolar DevMAPU01HL122626 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI AMBALAVANAN, NAMASIVAYAM, HAGOOD, JAMES S. · 2014 to 2018
$3.7M
Regulation of Fibroblast Phenotype in Lung FibrosisR01HL082818 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HAGOOD, JAMES S. · 2007 to 2017
$3.7M
NHLBI NIH HHS P01 HL119165NHLBI NIH HHS R01 HL082818NHLBI NIH HHS U01 HL122626
6 · The paper itself

Abstract

Bone marrow-derived mesenchymal stem cells (MSC) have been promoted for multiple therapeutic applications. Many beneficial effects of MSCs are paracrine, dependent on extracellular vesicles (EVs). Although MSC-derived EVs (mEVs) are beneficial for acute lung injury and pulmonary fibrosis, mechanisms of mEV uptake by lung fibroblasts and their effects on myofibroblastic differentiation have not been established. We demonstrate that mEVs, but not fibroblast EVs (fEVs), suppress TGFβ1-induced myofibroblastic differentiation of normal and idiopathic pulmonary fibrosis (IPF) lung fibroblasts. MEVs display increased time- and dose-dependent cellular uptake compared to fEVs. Removal or blocking of Thy-1, or blocking Thy-1-beta integrin interactions, decreased mEV uptake and prevented suppression of myofibroblastic differentiation. MicroRNAs (miRs) 199a/b-3p, 21-5p, 630, 22-3p, 196a-5p, 199b-5p, 34a-5p and 148a-3p are selectively packaged in mEVs. In silico analyses indicated that IPF lung fibroblasts have increased expression of genes that are targets of mEV-enriched miRs. MiR-630 mimics blocked TGFβ1 induction of CDH2 in normal and IPF fibroblasts, and antagomiR-630 abrogated the effect of mEV on CDH2 expression. These data suggest that the interaction of Thy-1 with beta integrins mediates mEV uptake by lung fibroblasts, which blocks myofibroblastic differentiation, and that mEVs are enriched for miRs that target profibrotic genes up-regulated in IPF fibroblasts.

Indexed as

Cell DifferentiationExtracellular VesiclesFibroblastsHumansIdiopathic Pulmonary FibrosisLungMesenchymal Stem CellsMyofibroblastsThy-1 AntigensTransforming Growth Factor beta1Thy-1 AntigensTransforming Growth Factor beta1

Identifiers

PMID29273797
PMCPMC5741716
OpenAlexW2776317681

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.