Evidence map›Paper›PMID 28170190›Full record

ArticleStem cells translational medicine2017

Enhanced Immunosuppression of T Cells by Sustained Presentation of Bioactive Interferon-γ Within Three-Dimensional Mesenchymal Stem Cell Constructs.

Joshua A Zimmermann, Marian H Hettiaratchi, Todd C McDevitt

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

Article in Stem cells translational medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
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

57 citing papers in PubMed, 78 citations in OpenAlex.

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  7. Persistent tailoring of MSC activation through genetic priming.Molecular therapy. Methods & clinical development · 2024
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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

3 authors at 3 institutions in 1 country.

Joshua A ZimmermannThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, Atlanta, Georgia, USA.
Marian H HettiaratchiThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, Atlanta, Georgia, USA.
Todd C McDevittGladstone Institute of Cardiovascular Disease, San Francisco, California, USA.
Georgia Institute of Technology · USGladstone Institutes · USUniversity of California, San Francisco · US

Funding

Engaging University of California Stakeholders for Biorespository ResearchUL1TR000004 · NCATS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRANDIS, JENNIFER RUBIN · 2012 to 2015
$78.0M
Engineering Mesenchymal Stem Cell Microenvironments to Promote ImmunomodulationR21AI109499 · NIAID · J. DAVID GLADSTONE INSTITUTES · PI MCDEVITT, TODD C · 2014 to 2015
$521k
NCATS NIH HHS UL1 TR000004NIAID NIH HHS R21 AI109499
6 · The paper itself

Abstract

The immunomodulatory activity of mesenchymal stem/stromal cells (MSCs) to suppress innate and adaptive immune responses offers a potent cell therapy for modulating inflammation and promoting tissue regeneration. However, the inflammatory cytokine milieu plays a critical role in stimulating MSC immunomodulatory activity. In particular, interferon-γ (IFN-γ)-induced expression of indoleamine 2,3-dioxygenase (IDO) is primarily responsible for MSC suppression of T-cell proliferation and activation. Although pretreatment with IFN-γ is commonly used to prime MSCs for immunomodulatory activity prior to transplantation, the transient effects of pretreatment may limit the potential of MSCs to potently modulate immune responses. Therefore, the objective of this study was to investigate whether microparticle-mediated presentation of bioactive IFN-γ within three-dimensional spheroidal MSC aggregates could precisely regulate and induce sustained immunomodulatory activity. Delivery of IFN-γ via heparin-microparticles within MSC aggregates induced sustained IDO expression during 1 week of culture, whereas IDO expression by IFN-γ-pretreated MSC spheroids rapidly decreased during 2 days. Furthermore, sustained IDO expression induced by IFN-γ-loaded microparticles resulted in an increased and sustained suppression of T-cell activation and proliferation in MSC cocultures with CD3/CD28-activated peripheral blood mononuclear cells. The increased suppression of T cells by MSC spheroids containing IFN-γ-loaded microparticles was dependent on induction of IDO and supported by affecting monocyte secretion from pro- to anti-inflammatory cytokines. Altogether, microparticle delivery of IFN-γ within MSC spheroids provides a potent means of enhancing and sustaining immunomodulatory activity to control MSC immunomodulation after transplantation and thereby improve the efficacy of MSC-based therapies aimed at treating inflammatory and immune diseases. Stem Cells Translational Medicine 2017;6:223-237.

Indexed as

Immunosuppression TherapyAnimalsAnti-Inflammatory AgentsCell Culture TechniquesCell-Derived MicroparticlesCell ProliferationHeparinHumansImmunomodulationIndoleamine-Pyrrole 2,3,-DioxygenaseInterferon-gammaLymphocyte ActivationMesenchymal Stem CellsMonocytesSolubilitySpheroids, CellularAnti-Inflammatory AgentsHeparinIndoleamine-Pyrrole 2,3,-DioxygenaseInterferon-gammaCellularImmunomodulationIndoleamine 2,3-dioxygenaseMesenchymal stromal cellsSpheroids

Identifiers

PMID28170190
PMCPMC5442746
OpenAlexW2500409440

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.