Evidence map›Paper›PMID 40515654›Full record

ArticleStem cells translational medicine2025

Initial or continuous coculture with umbilical cord-derived mesenchymal stromal cells facilitates in vitro expansion of human regulatory T-cell subpopulations.

Qifeng Ou, Sarah Cormican, Rachael Power, Sarah Hontz, Shirley A Hanley, Md Nahidul Islam, Georgina Shaw, Laura M Deedigan, Emma Horan, Stephen J Elliman and 4 more

Abstract read
In one paragraph

Article in Stem cells translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. 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

14 authors.

Qifeng OuRegenerative Medicine Institute (REMEDI) at CÚRAM Research Ireland Centre for Medical Devices, School of Medicine, University of Galway, Galway H19 TK33, Ireland.ORCID 0000-0002-8189-2543
Sarah CormicanRegenerative Medicine Institute (REMEDI) at CÚRAM Research Ireland Centre for Medical Devices, School of Medicine, University of Galway, Galway H19 TK33, Ireland.
Rachael PowerRegenerative Medicine Institute (REMEDI) at CÚRAM Research Ireland Centre for Medical Devices, School of Medicine, University of Galway, Galway H19 TK33, Ireland.
Sarah HontzRegenerative Medicine Institute (REMEDI) at CÚRAM Research Ireland Centre for Medical Devices, School of Medicine, University of Galway, Galway H19 TK33, Ireland.
Shirley A HanleyFlow Cytometry Core Facility, Biomedical Sciences, University of Galway, Galway H19 TK33, Ireland.
Md Nahidul IslamSchool of Biological and Chemical Sciences, College of Science and Engineering, University of Galway, Galway H19 TK33, Ireland.
Georgina ShawRegenerative Medicine Institute (REMEDI) at CÚRAM Research Ireland Centre for Medical Devices, School of Medicine, University of Galway, Galway H19 TK33, Ireland.
Laura M DeediganOrbsen Therapeutics Ltd., Dangan, Galway H91 A3EF, Ireland.
Emma HoranOrbsen Therapeutics Ltd., Dangan, Galway H91 A3EF, Ireland.
Stephen J EllimanOrbsen Therapeutics Ltd., Dangan, Galway H91 A3EF, Ireland.
Barbara FazekasRegenerative Medicine Institute (REMEDI) at CÚRAM Research Ireland Centre for Medical Devices, School of Medicine, University of Galway, Galway H19 TK33, Ireland.
Janusz KrawczykRegenerative Medicine Institute (REMEDI) at CÚRAM Research Ireland Centre for Medical Devices, School of Medicine, University of Galway, Galway H19 TK33, Ireland.
Neema NegiRegenerative Medicine Institute (REMEDI) at CÚRAM Research Ireland Centre for Medical Devices, School of Medicine, University of Galway, Galway H19 TK33, Ireland.
Matthew D GriffinRegenerative Medicine Institute (REMEDI) at CÚRAM Research Ireland Centre for Medical Devices, School of Medicine, University of Galway, Galway H19 TK33, Ireland.ORCID 0000-0002-8701-8056

Funding

China Scholarship Council PhD Fellowship 202106370032CÚRAM 13/RC/2073_P2European CommissionEuropean Union's Horizon 2020 Marie Skłodowska-Curie 713690Health and Social Care Research and Development DivisionHealth Research Board 203930/B/16/ZHealth Service Executive National Doctors Training and PlanningHealth Service Executive of IrelandHorizon 2020 Collaborative Health Project NEPHSTROM 634086Irish Clinical Academic Training (ICAT) ProgrammeIrish Research Council Enterprise Partnership Postdoctoral Fellowship EPSPD/2017/106MedTrainScience Foundation IrelandScience Foundation Ireland Research CentresWellcome Trust 203930/B/16/Z
6 · The paper itself

Abstract

Clinical trials have demonstrated the safety and potential efficacy of ex vivo expanded regulatory T cells (Tregs) for immune-mediated diseases. Nonetheless, achieving consistent and timely Treg yield and purity remains challenging. We aimed to evaluate the potential to enhance culture expansion of primary human total Treg (CD4+/CD25+/CD127lo) and Treg subpopulations through coculture with human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs). In 14- to 21-day anti-CD3/anti-CD28-, interleukin-2-, and rapamycin-containing cultures, fluorescence-activated cell sorting (FACS)-purified total Treg underwent 4-fold greater expansion following hUC-MSC coculture. Potency to suppress T effector cell (Teff) proliferation was equivalent for hUC-MSC-cocultured and control Tregs and correlated with the expression of HLA-DR, CD39, and inducible costimulator (ICOS). The impact of hUC-MSC coculture on ex vivo expansion of 3 FACS-purified Treg subpopulations [CD45RA+ (Subtype I), CD45RA-HLA-DR+ (Subtype II), and CD45RA-HLA-DR- (Subtype III)] was then investigated. Both initial and continuous hUC-MSC coculture yielded significantly higher fold expansion of each Treg subpopulation compared to control. However, the magnitude of enhancement was substantially greater for non-naive (Subtypes II and III) than for naive (Subtype I) Treg. Coculture with hUC-MSC increased HLA-DR expression of all 3 expanded Treg subpopulations while maintaining comparable Teff suppressive potency. For non-naive Treg (Subtypes II and III), both initial and continuous hUC-MSC coculture also increased the final %Foxp3+ and %Helios+. Thus, coculture with clinical-grade hUC-MSC substantially enhances the ex vivo yield, preserves the suppressive potency, and modulates HLA-DR expression of FACS-purified Treg subpopulations with greatest effect on non-naive (CD45RA-) Treg. The findings have potential to facilitate identification, functional characterization, and manufacturing of Treg subpopulations with distinct therapeutic benefits.

Indexed as

Mesenchymal Stem CellsT-Lymphocytes, RegulatoryUmbilical CordCell ProliferationCells, CulturedCoculture TechniquesHumanscell manufacturingcell therapyclinical translationculture expansionimmunological diseasesmesenchymal stromal cellsregulatory T cellssubpopulationsyield

Identifiers

PMID40515654
PMCPMC12166524

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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.