Evidence mapPaperPMID 42007763Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2026

The PPARβ/Delta-Induced Mesenchymal Stromal Cell Secretome Has Cytoprotective Effects via ANGPTL4 in a Pre-Clinical Model of Acute Lung Inflammation.

Courteney Tunstead, Molly Dunlop, Sinéad Ryan, Evelina Volkova, Evangeline Johnston, Sabrina Batah, Claudia C Dos Santos, Bairbre McNicholas, Claire Masterson, John G Laffey and 1 more

Abstract read
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

11 authors.

Courteney TunsteadCellular Immunology Lab, Department of Biology, Maynooth University, Maynooth, Ireland.
Molly DunlopCellular Immunology Lab, Department of Biology, Maynooth University, Maynooth, Ireland.
Sinéad RyanCellular Immunology Lab, Department of Biology, Maynooth University, Maynooth, Ireland.
Evelina VolkovaCellular Immunology Lab, Department of Biology, Maynooth University, Maynooth, Ireland.
Evangeline JohnstonCellular Immunology Lab, Department of Biology, Maynooth University, Maynooth, Ireland.
Sabrina BatahKeenan Research Centre for Biomedical Research, St. Michael's Hospital, Toronto, Ontario, Canada.
Claudia C Dos SantosKeenan Research Centre for Biomedical Research, St. Michael's Hospital, Toronto, Ontario, Canada.
Bairbre McNicholasAnesthesia and Intensive Care Medicine, School of Medicine, College of Medicine Nursing and Health Sciences, University of Galway, Galway, Ireland.
Claire MastersonAnesthesia and Intensive Care Medicine, School of Medicine, College of Medicine Nursing and Health Sciences, University of Galway, Galway, Ireland.
John G LaffeyAnesthesia and Intensive Care Medicine, School of Medicine, College of Medicine Nursing and Health Sciences, University of Galway, Galway, Ireland.
Karen EnglishCellular Immunology Lab, Department of Biology, Maynooth University, Maynooth, Ireland.ORCID https://orcid.org/0000-0002-7932-4256

Funding

Science Foundation Ireland (SFI) 20/FFP-A/8948
6 · The paper itself

Abstract

Human bone marrow-derived mesenchymal stromal cells (hBM-MSCs) are known to exert immunomodulatory and pro-reparative effects in vivo. This makes hBM-MSCs an enticing therapeutic candidate for inflammatory diseases, such as acute respiratory distress syndrome (ARDS). The ARDS microenvironment is complex and contains an abundance of free fatty acids (FFAs), which are known to differentially impact MSC functionality. PPARβ/δ is a ubiquitously expressed nuclear receptor that is activated in response to FFA-binding. PPARβ/δ has been shown to impact the therapeutic efficacy of mouse MSCs. This study sought to investigate the impact of PPARβ/δ-modulation on human MSC functionality in vitro and in vivo. hBM-MSCs were exposed to a synthetic PPARβ/δ agonist/antagonist in the presence or absence of ARDS patient serum and the immunomodulatory and pro-reparative capacity of the MSC secretome was investigated using in vitro assays and a pre-clinical model of LPS-induced acute lung inflammation (ALI). Our results highlighted enhanced pro-reparative capacity of PPARβ/δ-agonized hBM-MSCs secretome in CALU-3 lung epithelial cells, mediated by MSC derived angiopoietin-like 4 (ANGPTL4). PPARβ/δ-induced ANGPTL4-high MSC secretome facilitated enhanced endothelial barrier integrity in the lungs of ALI mice. Therapeutic effects of PPARβ/δ-agonized hBM-MSCs secretome were further enhanced by licensing MSCs with human ARDS patient serum. ARDS-licensed PPARβ/δ-induced ANGPTL4-high MSC secretome had reduced clinical score and weight loss. The role ANGPL4 in these protective effects was confirmed using an anti-ANGPTL4 antibody. These findings conclude that the MSC secretome therapeutic effects can be enhanced both in vitro and in vivo through licensing strategies that upregulate the angiogenic factor ANGPTL4.

Indexed as

Acute Lung InjuryAngiopoietin-Like Protein 4Mesenchymal Stem CellsPneumoniaPPAR-betaPPAR deltaAnimalsCells, CulturedDisease Models, AnimalHumansLipopolysaccharidesMaleMiceMice, Inbred C57BLRespiratory Distress SyndromeAngiopoietin-Like Protein 4ANGPTL4 protein, humanLipopolysaccharidesPPAR-betaPPAR deltaANGPTL4ARDSlung reapirMSCPPARβ/δ

Identifiers

PMID42007763
PMCPMC13094458

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.