Evidence map›Paper›PMID 32339220›Full record

ArticleCardiovascular research2021

Ex vivo Ikkβ ablation rescues the immunopotency of mesenchymal stromal cells from diabetics with advanced atherosclerosis.

Ozge Kizilay Mancini, David N Huynh, Liliane Menard, Dominique Shum-Tim, Huy Ong, Sylvie Marleau, Ines Colmegna, Marc J Servant

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

Article in Cardiovascular research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

10 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Research progress of stem cells in the treatment of atherosclerosis.Frontiers in cell and developmental biology · 2025
    Review
  5. Review
  6. Review
  7. Review
  8. Article
  9. Nutrients · 2022
    Article
  10. 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

8 authors at 2 institutions in 1 country.

Ozge Kizilay ManciniFaculty of Pharmacy, University of Montreal, C.P. 6128, Succursale Centre-Ville, Montréal, QC H3C 3J7, Canada.
David N HuynhFaculty of Pharmacy, University of Montreal, C.P. 6128, Succursale Centre-Ville, Montréal, QC H3C 3J7, Canada.
Liliane MenardFaculty of Pharmacy, University of Montreal, C.P. 6128, Succursale Centre-Ville, Montréal, QC H3C 3J7, Canada.
Dominique Shum-TimDivision of Cardiac Surgery Department of Surgery, McGill University, Montreal, QC H4A 3J1, Canada.
Huy OngFaculty of Pharmacy, University of Montreal, C.P. 6128, Succursale Centre-Ville, Montréal, QC H3C 3J7, Canada.
Sylvie MarleauFaculty of Pharmacy, University of Montreal, C.P. 6128, Succursale Centre-Ville, Montréal, QC H3C 3J7, Canada.
Ines ColmegnaDivision of Rheumatology, Department of Medicine, McGill University, Montreal, QC H4A 3J1, Canada.
Marc J ServantFaculty of Pharmacy, University of Montreal, C.P. 6128, Succursale Centre-Ville, Montréal, QC H3C 3J7, Canada.
Université de Montréal · CAMcGill University · CA

Funding

CIHR MOP-123482CIHR MOP 125857
6 · The paper itself

Abstract

aimsDiabetes is a conventional risk factor for atherosclerotic cardiovascular disease and myocardial infarction (MI) is the most common cause of death among these patients. Mesenchymal stromal cells (MSCs) in patients with type 2 diabetes mellitus (T2DM) and atherosclerosis have impaired ability to suppress activated T-cells (i.e. reduced immunopotency). This is mediated by an inflammatory shift in MSC-secreted soluble factors (i.e. pro-inflammatory secretome) and can contribute to the reduced therapeutic effects of autologous T2DM and atherosclerosis-MSC post-MI. The signalling pathways driving the altered secretome of atherosclerosis- and T2DM-MSC are unknown. Specifically, the effect of IκB kinase β (IKKβ) modulation, a key regulator of inflammatory responses, on the immunopotency of MSCs from T2DM patients with advanced atherosclerosis has not been studied. METHODS AND

resultsMSCs were isolated from adipose tissue obtained from patients with (i) atherosclerosis and T2DM (atherosclerosis+T2DM MSCs, n = 17) and (ii) atherosclerosis without T2DM (atherosclerosis MSCs, n = 17). MSCs from atherosclerosis+T2DM individuals displayed an inflammatory senescent phenotype and constitutively expressed active forms of effectors of the canonical IKKβ nuclear factor-κB transcription factors inflammatory pathway. Importantly, this constitutive pro-inflammatory IKKβ signature resulted in an altered secretome and impaired in vitro immunopotency and in vivo healing capacity in an acute MI model. Notably, treatment with a selective IKKβ inhibitor or IKKβ knockdown (KD) (clustered regularly interspaced short palindromic repeats/Cas9-mediated IKKβ KD) in atherosclerosis+T2DM MSCs reduced the production of pro-inflammatory secretome, increased survival, and rescued their immunopotency both in vitro and in vivo.

conclusionsConstitutively active IKKβ reduces the immunopotency of atherosclerosis+T2DM MSC by changing their secretome composition. Modulation of IKKβ in atherosclerosis+T2DM MSCs enhances their myocardial repair ability.

Indexed as

AgedAnimalsAtherosclerosisCase-Control StudiesCell ProliferationCells, CulturedCellular SenescenceCoculture TechniquesDiabetes Mellitus, Type 2Disease Models, AnimalFemaleHumansI-kappa B KinaseInflammation MediatorsLymphocyte ActivationMaleI-kappa B KinaseIKBKB protein, humanInflammation MediatorsProtein Kinase InhibitorsIKK beta signallingImmunopotencyInflammationMesenchymal stromal cells

Identifiers

PMID32339220
PMCPMC7898947
OpenAlexW3020277278

What OpenQuestion holds

Textmetadata
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.