The role of cytokine licensing in shaping the therapeutic potential of wharton’s jelly MSCs: metabolic shift towards immunomodulation at the expense of differentiation

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F25%3A00619413" target="_blank" >RIV/68378041:_____/25:00619413 - isvavai.cz</a>

Alternative codes found

RIV/86652036:_____/25:00619413 RIV/68378271:_____/25:00619413 RIV/67985823:_____/25:00619499 RIV/00216208:11130/25:10499787 RIV/00216208:11310/25:10499787

Result on the web

<a href="https://stemcellres.biomedcentral.com/articles/10.1186/s13287-025-04309-2#rightslink" target="_blank" >https://stemcellres.biomedcentral.com/articles/10.1186/s13287-025-04309-2#rightslink</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s13287-025-04309-2" target="_blank" >10.1186/s13287-025-04309-2</a>

Result language

angličtina

Original language name

The role of cytokine licensing in shaping the therapeutic potential of wharton’s jelly MSCs: metabolic shift towards immunomodulation at the expense of differentiation

Original language description

Background: Cytokine licensing with pro-inflammatory molecules, such as tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), has emerged as a promising strategy to enhance the therapeutic potential of multipotent mesenchymal stromal cells (MSCs). While licensing has demonstrated benefits for immunomodulation, its effects on other key MSC functions, including differentiation and paracrine activity, remain incompletely explored. In this study, we evaluated the transcriptomic, metabolomic, and functional changes induced by short-term TNF-α/IFN-γ priming of Wharton’s jelly-derived MSCs (WJ-MSCs).nMethods: WJ-MSCs were expanded and exposed to TNF-α and IFN-γ (10 ng/ml each) for 24 h. Transcriptomic analysis was performed using RNA sequencing to identify differentially expressed genes related to immune modulation and lineage commitment. Metabolomic profiling was conducted using high-resolution mass spectrometry to assess changes in metabolic pathways. Functional assays evaluated the effects of cytokine priming on induced differentiation and growth factor secretion.nResults: Cytokine licensing induced notable alterations in gene expression, upregulating pathways linked to immune response, inflammation, and cytokine signalling. However, short-term cytokine treatment significantly attenuated the osteogenic and adipogenic differentiation of MSCs, as evidenced by the reduced expression of RUNX2, ALP, CEBPA, and PPARG. The priming had a negligible effect on EGF, FGF-2, HGF, LIF, and SCF secretion. The production of VEGF-A and VEGF-C was elevated, although the levels remained low. Metabolomic analysis revealed enhanced kynurenine pathway activity, indicative of increased tryptophan catabolism, accompanied by elevated levels of fatty acids and polyamines.nConclusions: Our findings demonstrate that TNF-α/IFN-γ priming reprograms WJ-MSCs by enhancing their immunomodulatory capacity at the expense of differentiation potential. These results highlight the need for tailored strategies to optimize MSC functionality for specific clinical applications.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10601 - Cell biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Stem Cell Research & Therapy

ISSN

1757-6512

e-ISSN

1757-6512

Volume of the periodical

16

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

17

Pages from-to

199

UT code for WoS article

001471452100002

EID of the result in the Scopus database

2-s2.0-105003275843