Effect of Preconditioned Mesenchymal Stromal Cells on Early Microvascular Disturbance in a Mouse Sepsis Model

Septic patients often die in a context of multiple organ dysfunction syndrome (MODS), despite the macro-hemodynamic parameters being normalized and after the onset of antibiotic therapy. Microcirculation injury during sepsis affects capillary permeability and leukocyte-endothelium interactions and is thought to be instrumental in organ injury. Several studies have demonstrated a beneficial effect of mesenchymal stromal cells (MSCs) injection on survival and organ dysfunctions in sepsis models. In vivo activity of MSCs also appears to be very much dependent on the information provided before injection. Indeed preconditioning by interferon gamma (IFN gamma; MSC-IFN gamma) increases immunosuppressive capacity of MSCs in vitro and in vivo. Therefore, the objective was to evaluate the effect of MSC naive or IFN gamma preconditioned on leukocyte-endothelium interactions in a polymicrobial sepsis model by intraperitoneal feces injection. Six hours (H6) after this induction, we used intravital microscopy in mice cremaster muscle venules to study the flow behavior of leukocytes. Plasmas were harvested to evaluate inflammation level and endothelial activation. We showed that MSC-IFN gamma have a beneficial effect on microcirculation, by increasing the flow of white blood cells (WBCs) and the percentage of venules containing flowing WBCs, by significantly reducing the adhesion of WBCs and by increasing the average red blood cell velocity (V-RBC). In conclusion, our results suggest that intravenous injection of preconditioned MSC-IFN gamma improves microvascular hemodynamics in early phases of sepsis.