Conclusions
We conclude that MenSCs in combination with AB enhance survival in CLP-induced sepsis by acting on multiples targets. MenSCs thus constitute a feasible approach for the future clinical treatment of sepsis.
Methods
The antimicrobial activity of MenSCs was determined in vitro through direct and indirect bacterial growth assays and the measurement of the expression levels of different antimicrobial peptides (AMPs) by quantitative reverse transcription-polymerase chain reaction. The therapeutic effect of MenSCs was determined in the cecal ligation and puncture (CLP) mouse model. Mice were then treated with antibiotics (AB) or MenSCs alone or in combination. The survival rates and histological and biochemical parameters were evaluated, and the systemic levels of pro- and anti-inflammatory cytokines as well as the response of specific lymphocyte subsets were determined by flow cytometry.
Results
MenSCs exerted an important antimicrobial effect in vitro, mediated by a higher expression of the AMP-hepcidin. In the CLP mouse model, MenSCs in synergy with AB (a) improved the survival rate (95 %) in comparison with saline (6 %), AB (73 %), and MenSCs alone (48 %) groups; (b) enhanced bacterial clearance in the peritoneal fluids and blood; (c) reduced organ injuries evaluated by lower concentrations of the liver enzymes alanine aminotransferase and aspartate aminotransferase; and (d) modulated the inflammatory response through reduction of pro- and anti-inflammatory cytokines without significant loss of T and B lymphocytes. Conclusions: We conclude that MenSCs in combination with AB enhance survival in CLP-induced sepsis by acting on multiples targets. MenSCs thus constitute a feasible approach for the future clinical treatment of sepsis.