Abstract
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.
Highlights
Polytrauma (PT) patients suffer from at least two significantly injured body regions and at least one physiological problem [1]
Mesenchymal stromal cells (MSC) treated with platelet lysate (PL), interleukin 1 beta (IL1B), PT cocktail high (PTCH) or PT cocktail low (PTCL) for 6 h or 24 h were compared to MSC in cell culture medium supplemented with AB-serum
Meduri and colleagues showed that high levels of IL1B and IL6 in plasma from acute respiratory distress syndrome (ARDS) patients predict a poor outcome in ARDS patients [20]
Summary
Polytrauma (PT) patients suffer from at least two significantly injured body regions and at least one physiological problem [1]. MSC are multipotent, plastic-adherent and have a fibroblast-like shape [9]. They express cluster of differentiation (CD)105, CD73 and CD90 and do not express CD45, CD34, CD14, CD11b, CD79A, CD19, human leucocyte antigen (HLA)-DP, HLA-DQ and HLA-DR [9]. They are used in clinical trials for various diseases due to their ability to migrate to the site of injury, multi-potency (replacement therapy), paracrine effect and immunomodulation (regenerative therapy) [10]. Moon and colleagues recommended culturing of MSC with serum from stroke patients as a promising preconditioning method to increase the therapeutic effect of MSC in stroke patients [15]
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