Combined treatment with MSC transplantation and neutrophil depletion ameliorates D-GalN/LPS-induced acute liver failure in rats

Abstract

The imbalance of immunity is an important pathogenesis of acute liver failure (ALF). Neutrophils are the hallmark of acute inflammation, which have an essential role in immune regulation. Mesenchymal stem cell (MSC) transplantation is a promising therapy in ALF treatment. Recent studies indicated a considerable connection between MSCs and neutrophils in immune regulation. To investigate changes in neutrophils in ALF rats after MSC transplantation, and to explore the therapeutic effect and mechanism of the combined treatment with MSC transplantation and neutrophil depletion in ALF. We employed monotherapy and the combination therapy with MSCs and anti-PMN serum in D-galactosamine (D-GalN)/lipopolysaccharides (LPS)-induced ALF rats. Rats were sacrificed at 6, 12 and 24h, respectively. Blood samples and liver tissues were collected. Hepatic injury, inflammatory cytokines (TNF-α, IL-1β and IL-10), chemokines (CXCL1 and CXCL2), the number and activity of neutrophils and animal survival were assessed at fixed times. MSC transplantation can effectively improve the liver function of ALF rats and reduce the number and activity of neutrophils in both peripheral blood and liver. Compared with MSC transplantation alone, anti-PMN treatment and co-treatment had a better result in diminishing neutrophils. The co-treatment also exhibited a better therapeutical effect in ALF rats compared with monotherapy. In this process, the expressions of inflammatory cytokines in the liver were consistent with liver function. The regulation of the neutrophil-related microenvironment is affected in D-GalN/LPS-induced ALF rats after MSC transplantation. The combined treatment with MSC transplantation and neutrophil depletion may have a better therapeutic effect in ALF rats.