Immunomodulatory properties of wound fluid-activated mesenchymal stem cells on peripheral blood mononuclear cells

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Introduction MSC possess immunomodulatory properties that are mediated via direct cell-cell contacts but also by paracrine stimuli. Pro-inflammatory cytokines such as TGF-β, TNF-α, IFN-γ or indoleamine-pyrrole 2,3-dioxygenase (IDO) can modify MSC in their effects and lead to an increase in immunosuppression. In the local postoperative environment, MSC and inflammatory cytokines converge, and it is still unclear whether the interaction of these components can influence the patients" clinical outcome. Methods MSC were preconditioned with wound fluid (WF) from drains after head and neck cancer surgery. After 5 days of co-culture of MSC and PBMC, the suppression of T cells was quantified by CFSE staining. IDO was measured by ELISA in the supernatants of the co-culture and a multi-analyte immunoassay was carried out to determine the secretion of the cytokines IL-10, TGF-β, TNF-α and IFN-γ. Results The proliferation rate of CD4+T cells was suppressed stronger in co-culture with WF-stimulated MSC than with unstimulated MSC. The expression of TNF-α was strongly inhibited in both co-culture groups. IDO, TGF-β, IFN-γ and IL-10 showed higher expression in both MSC groups compared to the control, and there were significant differences between the two MSC groups for IFN-γ and IL-10. Discussion Preconditioning of MSC with WF influences their immunomodulatory potential. It results in a suppression of the proliferation of CD4+T cells and an alteration in the expression of proinflammatory signaling molecules. The results appear particularly interesting for the question of whether surgical intervention can promote early local recurrences in tumor patients. Publication History Article published online: 19 April 2024 © 2024. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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