Abstract
Isolating mesenchymal stromal cell (MSC) subpopulations with improved quality based on specific surface markers, such as CD146, is one approach to enhance their therapeutic potential. However, there is limited information on the cytokine-boosted immunomodulatory mechanisms between CD146-expressing and non-expressing MSCs across various inflammatory conditions. This study seeks to address this gap. MSCs from the human periodontal ligament (hPDL-MSCs) were treated with interleukin-(IL)-1β, interferon-(IFN)-γ, or tumor necrosis factor-(TNF)-α, investigating the expression of IDO-1, PD-L1, PTGS-2, and TSG-6 between CD146+ and CD146− hPDL-MSCs. Additionally, the expression of the immunomediators was compared between CD146-depleted and -enriched populations, generated by magnetic-bead-sorting. CD146+ hPDL-MSCs exhibited a significantly higher proportion of IDO-1+ cells, enhanced expression levels in the presence of IL-1β or TNF-α, and higher IL-1β, IFN-γ, or TNF-α-induced PD-L1 protein expression. Conversely, the proportion of TSG-6+ hPDL-MSCs was significantly lower in CD146+ cells under basal conditions. In CD146-enriched hPDL-MSCs, the immunomediator expression was minimally elevated, with significant differences under specific conditions: a higher PD-L1 protein expression under basal conditions and in the presence of IFN-γ or TNF-α, as well as higher or lower PGE2 levels with TNF-α or IL-1β, respectively. These results suggest that the immunomediator expression in hPDL-MSCs alters with different CD146 surface expression. CD146+ hPDL-MSCs do not always show higher levels of immunomediator expression. Further research is necessary to isolate hPDL-MSC subpopulations with optimal potential for therapeutic applications.
Data availability
All data which support the conclusion are shown in the manuscript. The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
We acknowledge Vera Maierhofer and Phuong Quyngh Nguyen for their excellent technical assistance.
Funding
This research was funded in whole by the Austrian Science Fund (FWF). Grant Doi: https://doi.org/10.55776/P35037; Funding to Oleh Andrukhov. For open access purposes, the author has applied a CC BY public copyright license to any author-accepted manuscript version arising from this submission.
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C.B. planned the experimental design, performed data analysis and interpretation, and wrote the manuscript. O.M. isolated hPDL-MSCs from extracted teeth and helped in conducting the experiments. K.S. and A.K. performed the experiments. O.A. was involved in planning and designing the experiments, formal data analysis and interpretation, supervision, and project administration. All authors read and approved the final manuscript.
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Behm, C., Miłek, O., Schwarz, K. et al. Immunomediator expression in human periodontal ligament MSCs varies depending on surface CD146 expression. Sci Rep (2026). https://doi.org/10.1038/s41598-026-38627-z
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DOI: https://doi.org/10.1038/s41598-026-38627-z
