Evidence map›Paper›PMID 30364570›Full record

ArticleJournal of immunology and regenerative medicine2018

Dual IFN-γ/hypoxia priming enhances immunosuppression of mesenchymal stromal cells through regulatory proteins and metabolic mechanisms.

Holly M Wobma, Mariko Kanai, Stephen P Ma, Ying Shih, Hao Wei Li, Raimon Duran-Struuck, Robert Winchester, Shahar Goeta, Lewis M Brown, Gordana Vunjak-Novakovic

Abstract read
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In one paragraph

Article in Journal of immunology and regenerative medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
–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

43 citing papers in PubMed.

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  8. Human OX40L-CAR-TScience translational medicine · 2024
    Article
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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

10 authors.

Holly M WobmaDepartment of Biomedical Engineering, Columbia University, New York, NY, USA.
Mariko KanaiDepartment of Biomedical Engineering, Columbia University, New York, NY, USA.
Stephen P MaDepartment of Biomedical Engineering, Columbia University, New York, NY, USA.
Ying ShihDepartment of Biomedical Engineering, Columbia University, New York, NY, USA.
Hao Wei LiColumbia Center for Translational Immunology, Columbia University, New York, NY, USA.
Raimon Duran-StruuckDepartment of Pathobiology, University of Pennsylvania, Philadelphia, PA, USA.
Robert WinchesterDepartment of Pathology, Columbia University, New York, NY, USA.
Shahar GoetaQuantitative Proteomics and Metabolomics Center, Columbia University, New York, NY, USA.
Lewis M BrownQuantitative Proteomics and Metabolomics Center, Columbia University, New York, NY, USA.
Gordana Vunjak-NovakovicDepartment of Biomedical Engineering, Columbia University, New York, NY, USA.

Funding

Translational Bioreactors - Engineering Complex TissuesP41EB002520 · NIBIB · TUFTS UNIVERSITY MEDFORD · PI KAPLAN, DAVID L. · 2004 to 2018
$16.7M
NIBIB NIH HHS P41 EB002520
6 · The paper itself

Abstract

The immunosuppressive capacity of human mesenchymal stromal cells (MSCs) renders them promising candidates for treating diverse immune disorders. However, after hundreds of clinical trials, there are still no MSC therapies approved in the United States. MSCs require specific cues to adopt their immunosuppressive phenotype, and yet most clinical trials use cells expanded in basic culture medium and growth conditions. We propose that priming MSCs prior to administration will improve their therapeutic efficacy. Interferon-gamma (IFN-γ) priming are cues common to situations of immune escape that have individually shown promise as MSC priming cues but have not been systematically compared. Using mixed lymphocyte reactions, we show that priming MSCs with either cue alone improves T-cell inhibition. However, combining the two cues results in additive effects and markedly enhances the immunosuppressive phenotype of MSCs. We demonstrate that IFN-γ induces expression of numerous immunosuppressive proteins (IDO, PD-L1, HLA-E, HLA-G), whereas hypoxia switches MSCs to glycolysis, causing rapid glucose consumption and production of T-cell inhibitory lactate levels. Dual IFN-γ/hypoxia primed MSCs display both attributes and have even higher induction of immunosuppressive proteins over IFN-γ priming alone (IDO and HLA-G), which may reflect another benefit of metabolic reconfiguration.

Indexed as

hypoxiaimmunosuppressioninterferon gammaMesenchymal stromal cellsmetabolismpriming

Identifiers

PMID30364570
PMCPMC6197483

What OpenQuestion holds

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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.