Evidence map›Paper›PMID 27203438›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016

Mesenchymal Stem Cells Deliver Exogenous MicroRNA-let7c via Exosomes to Attenuate Renal Fibrosis.

Bo Wang, Kevin Yao, Brooke M Huuskes, Hsin-Hui Shen, Junli Zhuang, Catherine Godson, Eoin P Brennan, Jennifer L Wilkinson-Berka, Andrea F Wise, Sharon D Ricardo

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

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 251 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
251citing papers in PubMed, 7 pooled it
15.3field-weighted citation impact, top 1% 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

251 citing papers in PubMed, 7 syntheses or guidelines pooled it, 382 citations in OpenAlex.

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191 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

10 authors at 2 institutions in 2 countries.

Bo WangDepartment of Anatomy and Developmental Biology, Monash University, Victoria, Australia.
Kevin YaoDepartment of Anatomy and Developmental Biology, Monash University, Victoria, Australia.
Brooke M HuuskesDepartment of Anatomy and Developmental Biology, Monash University, Victoria, Australia.
Hsin-Hui ShenDepartment of Microbiology, Monash University, Victoria, Australia.
Junli ZhuangDepartment of Anatomy and Developmental Biology, Monash University, Victoria, Australia.
Catherine GodsonDiabetes Complications Research Centre, Conway Institute and School of Medicine, University College Dublin, Dublin, Ireland.
Eoin P BrennanDiabetes Complications Research Centre, Conway Institute and School of Medicine, University College Dublin, Dublin, Ireland.
Jennifer L Wilkinson-BerkaDepartment of Immunology, Monash University, Victoria, Australia.
Andrea F WiseDepartment of Anatomy and Developmental Biology, Monash University, Victoria, Australia.
Sharon D RicardoDepartment of Anatomy and Developmental Biology, Monash University, Victoria, Australia.
Monash University · AUUniversity College Dublin · IE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The advancement of microRNA (miRNA) therapies has been hampered by difficulties in delivering miRNA to the injured kidney in a robust and sustainable manner. Using bioluminescence imaging in mice with unilateral ureteral obstruction (UUO), we report that mesenchymal stem cells (MSCs), engineered to overexpress miRNA-let7c (miR-let7c-MSCs), selectively homed to damaged kidneys and upregulated miR-let7c gene expression, compared with nontargeting control (NTC)-MSCs. miR-let7c-MSC therapy attenuated kidney injury and significantly downregulated collagen IVα1, metalloproteinase-9, transforming growth factor (TGF)-β1, and TGF-β type 1 receptor (TGF-βR1) in UUO kidneys, compared with controls. In vitro analysis confirmed that the transfer of miR-let7c from miR-let7c-MSCs occurred via secreted exosomal uptake, visualized in NRK52E cells using cyc3-labeled pre-miRNA-transfected MSCs with/without the exosomal inhibitor, GW4869. The upregulated expression of fibrotic genes in NRK52E cells induced by TGF-β1 was repressed following the addition of isolated exosomes or indirect coculture of miR-let7c-MSCs, compared with NTC-MSCs. Furthermore, the cotransfection of NRK52E cells using the 3'UTR of TGF-βR1 confirmed that miR-let7c attenuates TGF-β1-driven TGF-βR1 gene expression. Taken together, the effective antifibrotic function of engineered MSCs is able to selectively transfer miR-let7c to damaged kidney cells and will pave the way for the use of MSCs for therapeutic delivery of miRNA targeted at kidney disease.

Indexed as

ActinsAnimalsBiological TransportCell EngineeringCollagenDisease Models, AnimalErbB ReceptorsExosomesExtracellular VesiclesFibrosisGene ExpressionGene Expression RegulationGene Transfer TechniquesHumansKidney DiseasesMaleActinsCollagenErbB ReceptorsMicroRNAs

Identifiers

PMID27203438
PMCPMC5088767
OpenAlexW2401390149

What OpenQuestion holds

Textmetadata
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.