Evidence map›Paper›PMID 30870158›Full record

ArticleAnesthesiology2019

Extracellular Vesicles from Interferon-γ-primed Human Umbilical Cord Mesenchymal Stromal Cells Reduce Escherichia coli-induced Acute Lung Injury in Rats.

Amir K Varkouhi, Mirjana Jerkic, Lindsay Ormesher, Stéphane Gagnon, Sakshi Goyal, Razieh Rabani, Claire Masterson, Chris Spring, Paul Z Chen, Frank X Gu and 3 more

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Anesthesiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed, 6 pooled it
5.1field-weighted citation impact, top 4% 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

74 citing papers in PubMed, 6 syntheses or guidelines pooled it, 104 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 5 countries.

Amir K VarkouhiFrom the Keenan Research Centre for Biomedical Science (A.K.V., M.J., L.O., S. Gagnon, S. Goyal, R.R., C.M., C.S., C.C.d.S., G.F.C., J.G.L.) Interdepartmental Division of Critical Care Medicine and Department of Critical Care (C.C.d.S., G.F.C., J.G.L.) Department of Anesthesia (G.F.C., J.G.L.), St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada Department of Chemical Engineering and Applied Chemistry (F.X.G.), University of Toronto, Toronto, Ontario, Canada Department of Chemical Engineering, Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, Ontario, Canada (P.Z.C., F.X.G.) Department of Anesthesia, Royal College of Surgeons in Ireland, Dublin, Ireland (G.F.C.) Regenerative Medicine Institute (REMEDI) at CÚRAM Centre for Research in Medical Devices, National University of Ireland Galway, Galway, Ireland (J.G.L.).
Mirjana Jerkic
Lindsay Ormesher
Stéphane Gagnon
Sakshi Goyal
Razieh Rabani
Claire Masterson
Chris Spring
Paul Z Chen
Frank X Gu
Claudia C Dos Santos
Gerard F Curley
John G Laffey
St. Michael's Hospital · CAUnited States Nuclear Regulatory Commission · US

Funding

Canadian Institutes for Health Research
6 · The paper itself

Abstract

backgroundHuman umbilical cord mesenchymal stromal cells possess considerable therapeutic promise for acute respiratory distress syndrome. Umbilical cord mesenchymal stromal cells may exert therapeutic effects via extracellular vesicles, while priming umbilical cord mesenchymal stromal cells may further enhance their effect. The authors investigated whether interferon-γ-primed umbilical cord mesenchymal stromal cells would generate mesenchymal stromal cell-derived extracellular vesicles with enhanced effects in Escherichia coli (E. coli) pneumonia.

methodsIn a university laboratory, anesthetized adult male Sprague-Dawley rats (n = 8 to 18 per group) underwent intrapulmonary E. coli instillation (5 × 10 colony forming units per kilogram), and were randomized to receive (a) primed mesenchymal stromal cell-derived extracellular vesicles, (b) naïve mesenchymal stromal cell-derived extracellular vesicles (both 100 million mesenchymal stromal cell-derived extracellular vesicles per kilogram), or (c) vehicle. Injury severity and bacterial load were assessed at 48 h. In vitro studies assessed the potential for primed and naïve mesenchymal stromal cell-derived extracellular vesicles to enhance macrophage bacterial phagocytosis and killing.

resultsSurvival increased with primed (10 of 11 [91%]) and naïve (8 of 8 [100%]) mesenchymal stromal cell-derived extracellular vesicles compared with vehicle (12 of 18 [66.7%], P = 0.038). Primed-but not naïve-mesenchymal stromal cell-derived extracellular vesicles reduced alveolar-arterial oxygen gradient (422 ± 104, 536 ± 58, 523 ± 68 mm Hg, respectively; P = 0.008), reduced alveolar protein leak (0.7 ± 0.3, 1.4 ± 0.4, 1.5 ± 0.7 mg/ml, respectively; P = 0.003), increased lung mononuclear phagocytes (23.2 ± 6.3, 21.7 ± 5, 16.7 ± 5 respectively; P = 0.025), and reduced alveolar tumor necrosis factor alpha concentrations (29 ± 14.5, 35 ± 12.3, 47.2 ± 6.3 pg/ml, respectively; P = 0.026) compared with vehicle. Primed-but not naïve-mesenchymal stromal cell-derived extracellular vesicles enhanced endothelial nitric oxide synthase production in the injured lung (endothelial nitric oxide synthase/β-actin = 0.77 ± 0.34, 0.25 ± 0.29, 0.21 ± 0.33, respectively; P = 0.005). Both primed and naïve mesenchymal stromal cell-derived extracellular vesicles enhanced E. coli phagocytosis and bacterial killing in human acute monocytic leukemia cell line (THP-1) in vitro (36.9 ± 4, 13.3 ± 8, 0.1 ± 0.01%, respectively; P = 0.0004) compared with vehicle.

conclusionsExtracellular vesicles from interferon-γ-primed human umbilical cord mesenchymal stromal cells more effectively attenuated E. coli-induced lung injury compared with extracellular vesicles from naïve mesenchymal stromal cells, potentially via enhanced macrophage phagocytosis and killing of E. coli.

Indexed as

Acute Lung InjuryAnimalsEscherichia coli InfectionsExtracellular VesiclesHumansInterferon-gammaMacrophagesMaleMesenchymal Stem CellsPhagocytosisRatsRats, Sprague-DawleyUmbilical CordInterferon-gamma

Identifiers

PMID30870158
OpenAlexW2922377426

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.