The Effect of Exosomes Derived from Unrestricted Somatic Stem Cells on Murine Model of Sepsis.

Abstract

Sepsis is a systemic infection mainly caused by bacterial infections. Despite all efforts and advances in the treatment of sepsis, it is still considered one of the leading causes of death in hospitalized patients. Today, we have to use novel therapies and one of the most important is cell-free therapy. Exosomes have been shown to contain the contents of their parent cells and that they do not generate an immune response between different individuals which makes them a good candidate for transplantation. Unrestricted somatic stem cells (USSC), also known as mesenchymal stem cell progenitors due to their high proliferative capacity and low immune response, may be a novel therapy for sepsis. In this study, the effect of USSC-derived exosomes on sepsis was investigated using a mouse model. USSCs were isolated from human cord blood and characterized by flow cytometry and multi-lineage differentiation. The exosomes were then harvested from USSCs and characterized by transmission electron microscopy, Western blotting, and dynamic light scattering. The harvested exosomes were injected into the mouse model of sepsis. Biochemical, histological, molecular, and survival studies were performed in different groups. Our observations showed that USSC-derived exosomes can reduce inflammation in septic mice. Histopathologic and biochemical findings in the sham group showed multiorgan involvement, but these changes disappeared after 7 days of exosome administration. Moreover, the expression of IRAK-1 and TRAF-6 (main adapter molecules in signaling pathways of inflammation) was decreased through negative regulation by miR-146a after 72 h of exosome administration. A 2-fold increase in the level of IL-10 and a 2-fold decrease in the levels of IL-6 and TNF-α was observed. In conclusion, we showed that direct injection of USSC-derived exosomes can be one of the important methods for the treatment of various aspects of sepsis due to their immunomodulatory properties.