Evidence map›Paper›PMID 29212557›Full record

ArticleStem cell research & therapy2017

Preconditioning of murine mesenchymal stem cells synergistically enhanced immunomodulation and osteogenesis.

Tzuhua Lin, Jukka Pajarinen, Akira Nabeshima, Laura Lu, Karthik Nathan, Eemeli Jämsen, Zhenyu Yao, Stuart B Goodman

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

Article in Stem cell research & therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
4.8field-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

75 citing papers in PubMed, 109 citations in OpenAlex.

  1. Review
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  6. Prostaglandin EEXCLI journal · 2025
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  7. Review
  8. Article
  9. Advances in mesenchymal stem cells therapy for tendinopathies.Chinese journal of traumatology = Zhonghua chuang shang za zhi · 2024
    Review
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15 more citing papers are in PubMed but not listed here.

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

8 authors at 1 institution in 1 country.

Tzuhua LinDepartment of Orthopaedic Surgery, Stanford University School of Medicine, 450 Broadway Street, Redwood City, CA, 94063, USA.
Jukka PajarinenDepartment of Orthopaedic Surgery, Stanford University School of Medicine, 450 Broadway Street, Redwood City, CA, 94063, USA.
Akira NabeshimaDepartment of Orthopaedic Surgery, Stanford University School of Medicine, 450 Broadway Street, Redwood City, CA, 94063, USA.
Laura LuDepartment of Orthopaedic Surgery, Stanford University School of Medicine, 450 Broadway Street, Redwood City, CA, 94063, USA.
Karthik NathanDepartment of Orthopaedic Surgery, Stanford University School of Medicine, 450 Broadway Street, Redwood City, CA, 94063, USA.
Eemeli JämsenDepartment of Orthopaedic Surgery, Stanford University School of Medicine, 450 Broadway Street, Redwood City, CA, 94063, USA.
Zhenyu YaoDepartment of Orthopaedic Surgery, Stanford University School of Medicine, 450 Broadway Street, Redwood City, CA, 94063, USA.
Stuart B GoodmanDepartment of Orthopaedic Surgery, Stanford University School of Medicine, 450 Broadway Street, Redwood City, CA, 94063, USA. goodbone@stanford.edu.
Stanford University · US

Funding

Wear Particle Disease and NF-kappa B SignalingR01AR063717 · NIAMS · STANFORD UNIVERSITY · PI GOODMAN, STUART B · 2012 to 2021
$3.5M
Chemokine Directed Cell Trafficking during Continuous Infusion of Wear ParticlesR01AR055650 · NIAMS · STANFORD UNIVERSITY · PI GOODMAN, STUART B · 2007 to 2016
$3.3M
National Institute of Arthritis and Musculoskeletal and Skin Diseases 1R01AR063717National Institute of Arthritis and Musculoskeletal and Skin Diseases 2R01AR055650NIAMS NIH HHS R01 AR055650NIAMS NIH HHS R01 AR063717
6 · The paper itself

Abstract

backgroundMesenchymal stem cells (MSCs) are capable of immunomodulation and tissue regeneration, highlighting their potential translational application for treating inflammatory bone disorders. MSC-mediated immunomodulation is regulated by proinflammatory cytokines and pathogen-associated molecular patterns such as lipopolysaccharide (LPS). Previous studies showed that MSCs exposed to interferon gamma (IFN-γ) and the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) synergistically suppressed T-cell activation.

methodsIn the current study, we developed a novel preconditioning strategy for MSCs using LPS plus TNF-α to optimize the immunomodulating ability of MSCs on macrophage polarization.

resultsPreconditioned MSCs enhanced anti-inflammatory M2 macrophage marker expression (Arginase 1 and CD206) and decreased inflammatory M1 macrophage marker (TNF-α/IL-1Ra) expression using an in-vitro coculture model. Immunomodulation of MSCs on macrophages was significantly increased compared to the combination of IFN-γ plus TNF-α or single treatment controls. Increased osteogenic differentiation including alkaline phosphate activity and matrix mineralization was only observed in the LPS plus TNF-α preconditioned MSCs. Mechanistic studies showed that increased prostaglandin E2 (PGE2) production was associated with enhanced Arginase 1 expression. Selective cyclooxygenase-2 inhibition by Celecoxib decreased PGE2 production and Arginase 1 expression in cocultured macrophages.

conclusionsThe novel preconditioned MSCs have increased immunomodulation and bone regeneration potential and could be applied to the treatment of inflammatory bone disorders including periprosthetic osteolysis, fracture healing/nonunions, and osteonecrosis.

Indexed as

Alkaline PhosphataseAnimalsArginaseCelecoxibCell DifferentiationCoculture TechniquesCyclooxygenase 2DinoprostoneGene ExpressionImmunomodulationInterferon-gammaInterleukin 1 Receptor Antagonist ProteinLectins, C-TypeLipopolysaccharidesMacrophagesMaleAlkaline PhosphataseArg1 protein, mouseArginaseCelecoxibCyclooxygenase 2DinoprostoneIl1rn protein, mouseInterferon-gammaInterleukin 1 Receptor Antagonist ProteinLectins, C-TypeLipopolysaccharidesMannose-Binding LectinsMannose ReceptorPtgs2 protein, mouseReceptors, Cell SurfaceTumor Necrosis Factor-alphaImmunomodulationMacrophage polarizationMesenchymal stem cellsOsteogenesisProstaglandin E2

Identifiers

PMID29212557
PMCPMC5719931
OpenAlexW2774767882

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.