Evidence map›Paper›PMID 39207345›Full record

ArticleCytotherapy2025

Advancing immunomodulatory functions in mesenchymal stem/stromal cells through targeting the GATA6-mediated pathway.

Eric Chang-Yi Lin, Madison P Davis, Ming-Song Lee, Gui Ma, Wei Xu, Yuan-I Chang, Wan-Ju Li

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cytotherapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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.

Eric Chang-Yi LinDepartment of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, Wisconsin, USA; Institute of Physiology, College of Medicine, National Yang Ming Chiao Tung University, Taipei City, Taiwan.
Madison P DavisDepartment of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, Wisconsin, USA; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Ming-Song LeeDepartment of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, Wisconsin, USA; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Gui MaMcArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Wei XuMcArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Yuan-I ChangInstitute of Physiology, College of Medicine, National Yang Ming Chiao Tung University, Taipei City, Taiwan.
Wan-Ju LiDepartment of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, Wisconsin, USA; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA. Electronic address: Li@ortho.wisc.edu.

Funding

University of Wisconsin Institute for Clinical and Translational ResearchUL1TR002373 · NCATS · UNIVERSITY OF WISCONSIN-MADISON · PI ELIZABETH S BURNSIDE, Allan R. Brasier · 2017 to 2026
$75.9M
Ctr9 as a Predictive Biomarker for EZH2 Inhibitor SensitivityR01CA268183 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Wei Xu · 2022 to 2026
$2.0M
Blood-derived Induced Pluripotent Stem Cells for Cartilage RepairR01AR064803 · NIAMS · UNIVERSITY OF WISCONSIN-MADISON · PI LI, WAN-JU · 2015 to 2019
$1.6M
NCATS NIH HHS UL1 TR002373NCI NIH HHS R01 CA268183NIAMS NIH HHS R01 AR064803
6 · The paper itself

Abstract

BACKGROUND

aimsThe immunomodulatory capacity of mesenchymal stem/stromal cells (MSCs) is a key feature that makes them particularly valuable for regenerative medicine. However, this potential is affected by the chronological aging of the donors and the cell expansion procedures in culture. We have demonstrated that GATA binding protein 6 (GATA6) plays a pivotal role in the aging of MSCs and inhibiting GATA6 rejuvenates the characteristics of MSCs.

methodsIn this study, we compared the immunomodulatory capabilities of young and old MSC models, using induced pluripotent stem cells-derived rejuvenated MSCs (rMSCs) and their parental MSCs (pMSCs), respectively, to identify a key mechanism involved in the differential regulation of these capabilities. Additionally, we explored the role of GATA6 in mediating the mechanism.

resultsOur results demonstrated that rMSCs exhibited downregulated aging-associated regulators, including p53, p21 and GATA6, and showed enhanced suppression of T cell proliferation compared to pMSCs. Through analyzing our previous RNA-seq data and employing target gene knockdown, we determined both suppressors of cytokine signaling 3 (SOCS3) and interleukin 6 were involved in GATA6-induced regulation, collectively affecting the expression of programmed death ligand 1 (PDL1) in both pMSCs and rMSCs.

conclusionsOur findings underline the significance of the GATA6/SOCS3/PDL1 pathway in regulating aging-associated changes in MSC immunomodulatory activity, providing valuable insights into the potential use of rMSCs in the treatment of immune diseases and regenerative medicine.

Indexed as

Cell ProliferationGATA6 Transcription FactorImmunomodulationMesenchymal Stem CellsCell DifferentiationCellular SenescenceHumansInduced Pluripotent Stem CellsInterleukin-6Signal TransductionSuppressor of Cytokine Signaling 3 ProteinT-LymphocytesTumor Suppressor Protein p53GATA6 protein, humanGATA6 Transcription FactorInterleukin-6Suppressor of Cytokine Signaling 3 ProteinTumor Suppressor Protein p53cellular rejuvenationGATA6immunomodulationmesenchymal stem cellPDL1

Identifiers

PMID39207345
PMCPMC11668624

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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.