Mesenchymal stem cells preconditioned by staphylococcal enterotoxin B enhance survival and bacterial clearance in murine sepsis model

Abstract

Sepsis, a health-threatening progressive infectious disease, is the major cause of morbidity and mortality worldwide. Cell therapy using mesenchymal stromal cells (MSCs) is an innovative strategy with excessive therapeutic potential in the treatment of sepsis. Staphylococcal enterotoxin B (SEB) preconditioning aims to prolong the interval of survival of transplanted MSCs which induces the production of cytoprotective agents, anti-apoptotic and anti-inflammatory factors. The MSCs were preconditioned with an optimum dose of SEB (470 μmol/L). The expression levels of apoptosis genes and antibacterial activity of MSC and SEB-MSC and their conditioned medium (CM), as well as cell survival, were studied in vitro in an oxidative stress and serum deprivation condition. Following treatment of the septic mice with MSCs and SEB-MSCs, pro/anti-inflammatory cytokines, hematological factors, bacterial clearance and animal survival were assessed. The apoptotic and pro-inflammatory cytokine's genes expression was down-regulated while antibacterial peptides and anti-inflammatory cytokines were up-regulated in SEB-MSC-treated mice. The animal survival rates were improved; bacterial clearance was enhanced in the peritoneal fluids, blood and organs; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were reduced in blood, compared with saline and MSCs alone. This research concludes that transplantation of SEB-MSCs presents improved therapeutic effects on a live bacterial model of sepsis.

Keywords: antibacterial activity; mesenchymal stromal cells; preconditioning; sepsis; staphylococcal enterotoxin B; survival.