Inflammatory response of mesenchymal stromal cells after in vivo exposure with selected trauma-related factors and polytrauma serum

by Elisa Maria Amann, Alexander Groß, Markus Thomas Rojewski, Hans Armin Kestler, Miriam Kalbitz, Rolf Erwin Brenner, Markus Huber-Lang, Hubert Schrezenmeier

Polytrauma (PT) is a life-threatening disease and a major global burden of injury. Mesenchymal stromal cells (MSC) might be a therapeutic option for PT patients due to their anti-inflammatory and regenerative potential. We hypothesised that the inflammatory response of MSC is similar after exposure to selected trauma-relevant factors to sera from PT patients (PTS). Therefore, we investigated the effects of a mixture of defined factors, supposed to play a role on MSC in the early phase of PT. Additionally, in a translational approach we investigated the effect of serum from PT patients on MSC in vitro. MSC were incubated with a PT cocktail in physiological (PTCL) and supra-physiological (PTCH) concentrations or PTS. The effect on gene expression and protein secretion of MSC was analysed by RNA sequencing, ELISA and Multiplex assays of cell culture supernatant. Stimulation of MSC with PTCH, PTCL or IL1B led to significant up- or downregulation of 470, 183 and 469 genes compared to unstimulated MSC at 6 h. The intersection of differentially expressed genes in these groups was very high (92% overlap with regard to the PTCL group; treated for 6 h). Cytokine secretion profile of MSC revealed that IL1B mimics the effect of a more complex PT cocktail as well. However, there was only a minor proportion of overlapping differentially expressed genes between the MSC group stimulated with early times of PTS and the MSC group stimulated with PTCH, PTCL and IL1B. In conclusion, the effect of sera from PT patients on MSC activation cannot be simulated by the chosen trauma-relevant factors. Furthermore, we conclude that while IL1B might be useful to prime MSC prior to therapeutic application, it might not be as useful for the in vitro study of functional properties of MSC in the context of PT.