Evidence map›Paper›PMID 27388156›Full record

ArticleStem cell research & therapy2016

Human mesenchymal stromal/stem cells acquire immunostimulatory capacity upon cross-talk with natural killer cells and might improve the NK cell function of immunocompromised patients.

Rongtao Cui, Heike Rekasi, Monika Hepner-Schefczyk, Kai Fessmann, Robert M Petri, Kirsten Bruderek, Sven Brandau, Marcus Jäger, Stefanie B Flohé

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

Article in Stem cell research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 1 pooled it
4.2field-weighted citation impact, top 5% 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

40 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Translating MSC Therapy in the Age of Obesity.Frontiers in immunology · 2022
    Review
  15. Review
  16. Review
  17. Review
  18. Review
  19. Review
  20. Review
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

9 authors at 1 institution in 1 country.

Rongtao CuiDepartment of Orthopedics and Trauma Surgery, University Hospital Essen, University of Duisburg-Essen, Virchowstraße 171, D-45147, Essen, Germany.
Heike RekasiDepartment of Orthopedics and Trauma Surgery, University Hospital Essen, University of Duisburg-Essen, Virchowstraße 171, D-45147, Essen, Germany.
Monika Hepner-SchefczykDepartment of Orthopedics and Trauma Surgery, University Hospital Essen, University of Duisburg-Essen, Virchowstraße 171, D-45147, Essen, Germany.
Kai FessmannDepartment of Orthopedics and Trauma Surgery, University Hospital Essen, University of Duisburg-Essen, Virchowstraße 171, D-45147, Essen, Germany.
Robert M PetriDepartment of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Kirsten BruderekDepartment of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Sven BrandauDepartment of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Marcus JägerDepartment of Orthopedics and Trauma Surgery, University Hospital Essen, University of Duisburg-Essen, Virchowstraße 171, D-45147, Essen, Germany.
Stefanie B FlohéDepartment of Orthopedics and Trauma Surgery, University Hospital Essen, University of Duisburg-Essen, Virchowstraße 171, D-45147, Essen, Germany. stefanie.flohe@uk-essen.de.
University of Duisburg-Essen · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe suppressive effect of mesenchymal stromal/stem cells (MSCs) on diverse immune cells is well known, but it is unclear whether MSCs additionally possess immunostimulatory properties. We investigated the impact of human MSCs on the responsiveness of primary natural killer (NK) cells in terms of cytokine secretion.

methodsHuman MSCs were generated from bone marrow and nasal mucosa. NK cells were isolated from peripheral blood of healthy volunteers or of immunocompromised patients after severe injury. NK cells were cultured with MSCs or with MSC-derived conditioned media in the absence or presence of IL-12 and IL-18. C-C chemokine receptor (CCR) 2, C-C chemokine ligand (CCL) 2, and the interferon (IFN)-γ receptor was blocked by specific inhibitors or antibodies. The synthesis of IFN-γ and CCL2 was determined.

resultsIn the absence of exogenous cytokines, trace amounts of NK cell-derived IFN-γ licensed MSCs for enhanced synthesis of CCL2. In turn, MSCs primed NK cells for increased release of IFN-γ in response to IL-12 and IL-18. Priming of NK cells by MSCs occurred in a cell-cell contact-independent manner and was impaired by inhibition of the CCR2, the receptor of CCL2, on NK cells. CD56(bright) NK cells expressed higher levels of CCR2 and were more sensitive to CCL2-mediated priming by MSCs and by recombinant CCR2 ligands than cytotoxic CD56(dim) NK cells. NK cells from severely injured patients were impaired in cytokine-induced IFN-γ synthesis. Co-culture with MSCs or with conditioned media from MSCs and MSC/NK cell co-cultures from healthy donors improved the IFN-γ production of the patients' NK cells in a CCR2-dependent manner.

conclusionsA positive feedback loop driven by NK cell-derived IFN-γ and MSC-derived CCL2 increases the inflammatory response of cytokine-stimulated NK cells not only from healthy donors but also from immunocompromised patients. Therapeutic application of MSCs or their soluble factors might thus improve the NK function after severe injury.

Indexed as

Immunocompromised HostAdultAntibodiesCell CommunicationChemokine CCL2Coculture TechniquesCulture Media, ConditionedFemaleHumansImmunomodulationInterferon-gammaInterferon gamma ReceptorInterleukin-12Interleukin-18Killer Cells, NaturalMaleAntibodiesCCL2 protein, humanCCR2 protein, humanChemokine CCL2Culture Media, ConditionedIL18 protein, humanInterferon-gammaInterferon gamma ReceptorInterleukin-12Interleukin-18Receptors, CCR2Receptors, InterferonCCL2CCR2ChemokinesImmunosuppressionInjuryInterferon gammaMCP-1Mesenchymal stem cellsMesenchymal stromal cellsNatural killer cellsTrauma

Identifiers

PMID27388156
PMCPMC4937587
OpenAlexW2462691249

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.