IL-1β siRNA adenovirus benefits liver regeneration by improving mesenchymal stem cells survival after acute liver failure

Abstract

Background: Uncontrolled hapatic inflammatory response is regarded as the primary pathological mechanism of acute liver failure and impairs the regeneration of hepatocytes and stem cell grafts. Interleukin-1 plays a key role for activating immune and inflammatory response. Recently, siRNA has made quite a few progresses in treating inflammatory response.Aim. To assess the effect of IL-1β siRNA adenovirus on MSC and the therapeutic effect of MSC combined with IL-1β siRNA adenovirus in ALF.Material and methods. We implanted MSC or/and IL-1β siRNA adenovirus via the tail vein, using CCl4-induced ALF in a mice model. Mice were sacrificed at different time points. Blood samples and liver tissues were collected. Hepatic injury, liver regeneration, cytokines (CXCL1, IL-1β, IL-10, IL-6, VEGF and HGF), animal survival and vital MSC were assessed after cell transplantation.Results. MSC combined with IL-1β siRNA reduced the inflammatory levels and prevented liver failure. These animals administrated with MSC and IL-1β siRNA also exhibited improved liver regeneration and increased survival rates. Immunohistochemistry and fluorescence microscopy revealed the number of vital MSC in ALF + MSC + IL-1β siRNA group were significantly more than that in ALF + MSC group.Conclusion. IL-1β siRNA adenovirus could enhance MSC ability of tissue regeneration through increasing its survival rate. Accordingly, combination of IL-1β siRNA adenovirus and MSC had a synergistic effect on acute liver failure.