Evidence map›Paper›PMID 24648336›Full record

ArticleStem cells (Dayton, Ohio)2014

miR-335 correlates with senescence/aging in human mesenchymal stem cells and inhibits their therapeutic actions through inhibition of AP-1 activity.

María Tomé, Juan Carlos Sepúlveda, Mario Delgado, José A Andrades, Judith Campisi, Manuel A González, Antonio Bernad

Abstract read
In one paragraph

Article in Stem cells (Dayton, Ohio), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing 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

50 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Epigenetic mechanisms in stem cell therapies for achilles tendinopathy.Frontiers in cell and developmental biology · 2025
    Review
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. The Mechanism of Stem Cell Aging.Stem cell reviews and reports · 2022
    Review
  16. Review
  17. Article
  18. Article
  19. Article
  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

7 authors.

María ToméDepartment of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
Juan Carlos Sepúlveda
Mario Delgado
José A Andrades
Judith Campisi
Manuel A González
Antonio Bernad

Funding

CELLULAR SENESCENCE AND CONTROL OF GENE EXPRESSIONR37AG009909 · NIA · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI CAMPISI, JUDITH · 1995 to 2015
$7.6M
NIA NIH HHS R37 AG009909
6 · The paper itself

Abstract

MicroRNAs, small noncoding RNAs, regulate gene expression primarily at the posttranscriptional level. We previously found that miR-335 is critically involved in the regulation and differentiation capacity of human mesenchymal stem cells (hMSCs) in vitro. In this study, we investigated the significance of miR-335 for the therapeutic potential of hMSCs. Analysis of hMSCs in ex vivo culture demonstrated a significant and progressive increase in miR-335 that is prevented by telomerase. Expression levels of miR-335 were also positively correlated with donor age of hMSCs, and were increased by stimuli that induce cell senescence, such as γ-irradiation and standard O2 concentration. Forced expression of miR-335 resulted in early senescence-like alterations in hMSCs, including: increased SA-β-gal activity and cell size, reduced cell proliferation capacity, augmented levels of p16 protein, and the development of a senescence-associated secretory phenotype. Furthermore, overexpression of miR-335 abolished the in vivo chondro-osseous potential of hMSCs, and disabled their immunomodulatory capacity in a murine experimental model of lethal endotoxemia. These effects were accompanied by a severely reduced capacity for cell migration in response to proinflammatory signals and a marked reduction in Protein Kinase D1 phosphorylation, resulting in a pronounced decrease of AP-1 activity. Our results demonstrate that miR-335 plays a key role in the regulation of reparative activities of hMSCs and suggests that it might be considered a marker for the therapeutic potency of these cells in clinical applications.

Indexed as

Blotting, WesternCell DifferentiationCell MovementCellular SenescenceFlow CytometryFluorescent Antibody TechniqueHumansMesenchymal Stem CellsMicroRNAsReal-Time Polymerase Chain ReactionTranscription Factor AP-1Transduction, GeneticMicroRNAsMIRN335 microRNA, humanTranscription Factor AP-1AgingImmunotherapyMesenchymal stem cellsMicroRNA

Identifiers

PMID24648336
PMCPMC4207125

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Registered trials

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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.