Immunomodulatory effects and migratory activity of multipotent mesenchymal stromal cells in the posttraumatic inflammatory response
Auch gedruckt in der BibliothekW: W-H 14.456
Ressourcen- / MedientypDissertation, Text
Datum der Freischaltung2015-11-17
After a polytrauma (PT), the release of massive amounts of endogenous alarmins and inflammatory mediators often bears the risk of a systemic inflammatory response syndrome (SIRS) and multi-organ failure. Upon injury, levels of blood circulating multipotent mesenchymal stromal cells (MSC) increase. Aim of this study, thus, was to determine, if numbers of MSC also augment in the blood of PT patients. Since systemically administrated MSC are known to exert immunomodulatory effects, the systemic application of allogeneic MSC to PT patients might be a potential therapeutic option for the prevention of SIRS. Hence, the second aim of this study was to examine the effect of PT-associated cytokines and complement factors (C), alone or in a PT cocktail (PTC) containing interleukin (IL) 1B, IL6, IL8, C3a and C5a in concentrations measured after a PT, on MSC in vitro. The immunomodulatory effect of MSC was further investigated in a co-culture with macrophages. In summary, different populations of blood circulating CD45 negative, MSC marker positive cell populations increased upon a PT and peaked between 12 and 48 h thereafter. C3a proved to be a potent chemoattractant for MSC and the main mediator of chemotaxis within the PTC, while IL1B seemed to be solely responsible for the augmented gene and protein expression of matrix metallopeptidase 1, possibly implying a facilitated migration of MSC through collagen containing tissue under PT conditions. IL1B was also the crucial mediator of the PTC for the increased release of the immunomodulatory factors prostaglandin E2 and tumor necrosis factor-inducible gene 6 protein and the amplified gene expression levels of various chemokines. Since MSC downregulated tumor necrosis factor (TNF) secretion in PTC and high mobility group box protein 1 activated macrophages, systemically administered MSC might be able to affect the TNF secretion of sterile activated macrophages in a PT setting and in this way reduce the risk of SIRS.