PhD Scientific Days 2026

Poster Session 3.J - Theoretical and Translational Medicine

Functional Heterogeneity of Mesenchymal Stem Cells Assessed via Kynurenine-Mediated Immunosuppression

Name of the presenter

Vadicsku, Dorina

Institute/workplace of the presenter

Semmelweis University, Department of Internal Medicine and Haematology

Authors

Dorina Vadicsku¹, Flóra Demeter¹, Erika Kajdácsi^1,2, György Bihari¹, László Cervenak¹
1: Department of Internal Medicine and Hematology, Semmelweis University, Budapest
2: Research Group for Immunology and Hematology, Semmelweis University-HUN-REN-SU (Office for Supported Research Groups), Budapest

Text of the abstract

Malfunctioning of the immune system plays a key role in the pathogenesis of numerous autoimmune and neuroinflammatory diseases. Mesenchymal stem cells (MSCs), in addition to supporting tissue regeneration, possess significant immunosuppressive properties, which has led to extensive investigation of their therapeutic potential. Although their clinical use has been approved in certain indications, in other cases their application has been limited or even withdrawn due to high variability in efficacy. This suggests that substantial functional differences may exist among individual MSC lines.
One of the key mediators of the immunosuppressive effect of MSCs is the enzyme indoleamine-2,3-dioxygenase-1 (IDO-1), which degrades tryptophan into kynurenine. Since kynurenine levels can be reliably quantified, they serve as a robust functional readout for comparing the immunomodulatory activity of MSCs. Based on this, the aim of our study was to determine whether umbilical cord-derived MSC lines from different donors differ in their kynurenine production under untreated conditions and following interferon-gamma (IFN-γ) stimulation.
To address this, multiple MSC lines were treated with IFN-γ, after which the amount of kynurenine produced by the cells was measured. In addition, the effect of IDO-1 inhibition on kynurenine production was also investigated.
Our results clearly demonstrated that although IFN-γ activated the kynurenine pathway in all examined MSC lines, the magnitude of the response showed considerable variability. Differences between cell lines were already evident under untreated conditions (2-6 µM kynurenine), and this variability was further amplified upon dose-dependent IFN-γ stimulation (15-58 µM at 10 ng/ml IFN-γ, and 48-93 µM at 50 ng/ml). The concentration-dependent response and the decrease in kynurenine levels upon IDO-1 inhibition confirmed the biological relevance of the observed differences.
Our findings indicate that MSCs cannot be regarded as functionally uniform therapeutic entities. At the same time, the observed heterogeneity also represents an opportunity, as the careful selection and targeted characterization of MSC lines may enable the development of more personalized, effective, and reproducible cell-based therapies in the future.

Support: Project No.TKP2021-EGA-24(MOLORKIV), Project No.TKP2021-EGA-08