Evidence map›Paper›PMID 28739167›Full record

ArticleCytotherapy2017

Establishment of NF-κB sensing and interleukin-4 secreting mesenchymal stromal cells as an "on-demand" drug delivery system to modulate inflammation.

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

Open access · greenAbstract read
In one paragraph

Article in Cytotherapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
3.4field-weighted citation impact, top 7% 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, 47 citations in OpenAlex.

  1. Review
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  4. Therapeutic effects of MSCs, genetically modified MSCs, and NFĸB-inhibitor on chronic inflammatory osteolysis in aged mice.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2023
    Article
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  7. Modulation of TRPV4 protects against degeneration induced by sustained loading and promotes matrix synthesis in the intervertebral disc.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023
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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

7 authors at 1 institution in 1 country.

Tzuhua LinDepartment of Orthopaedic Surgery, Stanford University, Stanford, California, USA.
Jukka PajarinenDepartment of Orthopaedic Surgery, Stanford University, Stanford, California, USA.
Akira NabeshimaDepartment of Orthopaedic Surgery, Stanford University, Stanford, California, USA.
Laura LuDepartment of Orthopaedic Surgery, Stanford University, Stanford, California, USA.
Karthik NathanDepartment of Orthopaedic Surgery, Stanford University, Stanford, California, USA.
Zhenyu YaoDepartment of Orthopaedic Surgery, Stanford University, Stanford, California, USA.
Stuart B GoodmanDepartment of Orthopaedic Surgery, Stanford University, Stanford, California, USA; Department of Bioengineering, Stanford University, Stanford, California, USA. Electronic address: 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
NIAMS NIH HHS R01 AR055650NIAMS NIH HHS R01 AR063717
6 · The paper itself

Abstract

Chronic inflammation is associated with up-regulation of the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and excessive inflammatory cytokine secretion by M1 macrophages. The anti-inflammatory cytokine interleukin (IL)-4 converts pro-inflammatory M1 macrophages into an anti-inflammatory and tissue-regenerative M2 phenotype, thus reducing inflammation and enhancing tissue regeneration. We have generated NF-κB responsive, or constitutively active IL-4 expression lentiviral vectors transduced into murine bone marrow-derived mesenchymal stromal cells (MSCs). MSCs with a constitutively active IL-4 expression vector produced large quantities of IL-4 continuously, whereas IL-4 secretion was significantly induced by lipopolysaccharide (LPS) in the NF-κB sensing MSCs. In contrast, LPS had no effect on MSCs with IL-4 secretion driven by a constitutively active promoter. We also found that intermittent and continuous LPS treatment displayed distinct NF-κB activation profiles, and this regulation was independent of IL-4 signaling. The supernatant containing IL-4 from the LPS-treated MSCs suppressed M1 marker (inducible nitric oxide synthase [iNOS] and tumor necrosis factor alpha [TNFα]) expression and enhanced M2 marker (Arginase 1, CD206 and IL1 receptor antagonist [IL1Ra]) expression in primary murine macrophages. The IL-4 secretion at the basal, non-LPS induced level was sufficient to suppress TNFα and enhance Arginase 1 at a lower level, but had no significant effects on iNOS, CD206 and IL1Ra expression. Finally, IL-4 secretion at basal or LPS-induced levels significantly suppressed osteogenic differentiation of MSCs. Our findings suggest that the IL-4 secreting MSCs driven by NF-κB sensing or constitutive active promoter have great potential for mitigating the effects of chronic inflammation and promoting earlier tissue regeneration.

Indexed as

AnimalsCell DifferentiationCells, CulturedDrug Delivery SystemsInflammationInterleukin-4LipopolysaccharidesMacrophagesMaleMesenchymal Stem CellsMice, Inbred C57BLNF-kappa BNitric Oxide Synthase Type IIOsteogenesisPromoter Regions, GeneticSignal TransductionInterleukin-4LipopolysaccharidesNF-kappa BNitric Oxide Synthase Type IINos2 protein, mouseTumor Necrosis Factor-alphainterleukin-4macrophage polarizationmesenchymal stromal cellsNF-κB

Identifiers

PMID28739167
PMCPMC5563472
OpenAlexW2736775973

What OpenQuestion holds

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LicenceTDM
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.