0619499 - FGÚ 2026 RIV GB eng J - Journal Article
Rogulska, Olena - Vavřínová, E. - Vacková, Irena - Havelková, Jarmila - Gotvaldová, Klára - Abaffy, P. - Kubinová, Š. - Šíma, M. - Rössner ml., P. - Bačáková, Lucie - Jendelová, P. - Smolková, Katarína - Petrenko, Yuriy
The role of cytokine licensing in shaping the therapeutic potential of wharton’s jelly MSCs: metabolic shift towards immunomodulation at the expense of differentiation.
Stem Cell Research & Therapy. Roč. 16, č. 1 (2025), č. článku 199. ISSN 1757-6512. E-ISSN 1757-6512
R&D Projects: GA ČR(CZ) GA22-31457S; GA MŠMT(CZ) EH22_008/0004562; GA MZd(CZ) NU22-06-00016
Research Infrastructure: EATRIS-CZ IV - 90253
Institutional support: RVO:67985823
Keywords : multipotent mesenchymal stromal cells * Wharton’s jelly * cytokine priming * transcriptomics * metabolomics * adipogenic and osteogenic differentiation * secretome
OECD category: Cell biology
Impact factor: 7.1, year: 2023 ; AIS: 1.515, rok: 2023
Method of publishing: Open access
Result website:
https://doi.org/10.1186/s13287-025-04309-2DOI: https://doi.org/10.1186/s13287-025-04309-2

BackgroundCytokine licensing with pro-inflammatory molecules, such as tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), 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-alpha/IFN-gamma priming of Wharton's jelly-derived MSCs (WJ-MSCs).MethodsWJ-MSCs were expanded and exposed to TNF-alpha and IFN-gamma (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.ResultsCytokine 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.ConclusionsOur findings demonstrate that TNF-alpha/IFN-gamma 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.
Permanent Link: https://hdl.handle.net/11104/0366162
Research data: Zenodo