Evidence map›Paper›PMID 29562785›Full record

ArticleCell transplantation2018

Extracellular Vesicles Derived from Wharton's Jelly Mesenchymal Stem Cells Prevent and Resolve Programmed Cell Death Mediated by Perinatal Hypoxia-Ischemia in Neuronal Cells.

Marianne S Joerger-Messerli, Byron Oppliger, Marialuigia Spinelli, Gierin Thomi, Ivana di Salvo, Philipp Schneider, Andreina Schoeberlein

Open access · goldAbstract read
In one paragraph

Article in Cell transplantation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
3.4field-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

56 citing papers in PubMed, 74 citations in OpenAlex.

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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 at 2 institutions in 1 country.

Marianne S Joerger-Messerli1 Department of Obstetrics and Gynecology, Bern University Hospital (Inselspital), University of Bern, Bern, Switzerland.
Byron Oppliger1 Department of Obstetrics and Gynecology, Bern University Hospital (Inselspital), University of Bern, Bern, Switzerland.
Marialuigia Spinelli1 Department of Obstetrics and Gynecology, Bern University Hospital (Inselspital), University of Bern, Bern, Switzerland.
Gierin Thomi1 Department of Obstetrics and Gynecology, Bern University Hospital (Inselspital), University of Bern, Bern, Switzerland.
Ivana di Salvo1 Department of Obstetrics and Gynecology, Bern University Hospital (Inselspital), University of Bern, Bern, Switzerland.
Philipp Schneider1 Department of Obstetrics and Gynecology, Bern University Hospital (Inselspital), University of Bern, Bern, Switzerland.
Andreina Schoeberlein1 Department of Obstetrics and Gynecology, Bern University Hospital (Inselspital), University of Bern, Bern, Switzerland.
University Hospital of Bern · CHUniversity of Bern · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hypoxic-ischemic (HI) insult in the perinatal phase harbors a high risk of encephalopathy in the neonate. Brain cells undergo apoptosis, initiating neurodegeneration. So far, therapeutic approaches such as cooling remain limited. Transplantation of mesenchymal stem cells (MSCs) exhibits therapeutic success despite the short-time survival in the host brain, providing strong evidence that their beneficial effects are largely based on secreted factors, including extracellular vesicles (EVs). The aim of this study was to investigate the effects of human Wharton's jelly MSC (hWJ-MSC)-derived EVs on neuroprotection and neuroregeneration, using an in vitro model of oxygen-glucose deprivation/reoxygenation (OGD/R) mimicking HI injury in the mouse neuroblastoma cell line neuro2a (N2a). hWJ-MSC-derived EVs were isolated from cell culture supernatants by multistep centrifugation and identified by endosomal marker expression and electron microscopy. OGD/R significantly increased DNA fragmentation and caspase 3 ( Casp3) transcription in N2a cells relative to undamaged cells. OGD/R-mediated DNA fragmentation and Casp3 expression could be prevented as well as resolved by the addition of hWJ-MSC-derived EV before and after OGD, respectively. hWJ-MSC-derived EV also tended to increase the phosphorylation of the B cell lymphoma 2 (Bcl2) family member Bcl-2-antagonist of cell death (BAD) in N2a cells, when added prior or post OGD, thereby inactivating the proapoptotic function of BAD. Fluorescence confocal microscopy revealed the close localization of hWJ-MSC-derived EVs to the nuclei of N2a cells. Furthermore, EVs released their RNA content into the cells. The expression levels of the microRNAs (miRs) let-7a and let-7e, known regulators of Casp3, were inversely correlated to Casp3. Our data suggest that hWJ-MSC-derived EVs have the potential to prevent and resolve HI-induced apoptosis in neuronal cells in the immature neonatal brain. Their antiapoptotic effect seems to be mediated by the transfer of EV-derived let-7-5p miR.

Indexed as

AnimalsApoptosisCell Line, TumorCells, CulturedExtracellular VesiclesHypoxiaIn Situ Nick-End LabelingIschemiaMesenchymal Stem CellsMiceMicroRNAsNeuronsWharton JellyMicroRNAsmirnlet7 microRNA, humanapoptosisextracellular vesicles (EVs)let-7-5pneuroprotectionneuroregenerationoxygen–glucose deprivation/reoxygenation (OGD/R)

Identifiers

PMID29562785
PMCPMC6434490
OpenAlexW2793036467

What OpenQuestion holds

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LicenceCC BY-NC
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.