Administration of IL-1Ra Chitosan Nanoparticles Enhances the Therapeutic Efficacy of Mesenchymal Stem Cell Transplantation in Acute Liver Failure

Background and Aims. To investigate the synergistic effect of IL-1Ra administration and stem cell transplantation in swine suffering from acute liver failure (ALF), to elucidate the mechanism of IL-1Ra activity and to demonstrate mesenchymal stem cell (MSC) transplantation as a potential treatment for ALF. Methods. Thirty-five Chinese experimental mini-swine were divided into five groups randomly. Group A (n = 7) is the control group and all swine were injected with saline via portal veins. Group B (n = 7) received IL-1Ra via ear veins 6 h before receiving saline. Group C (n = 7) received MSC transplantation and all swine were injected with 8 x 10(7) MSCs via portal veins. Group D (n = 7) swine were treated with a combination of IL-1Ra and MSC transplantation E (n = 7) also received a combined treatment of both IL-1Ra and bone marrow (BM-MSC) transplantation, except that the IL-1Ra was in the form of chitosan nanoparticles. Liver function, level of cytokines and liver pathological changes were measured in the following 4 weeks. Results. IL-1Ra chitosan nanoparticles exhibited controlled-release ability in PBS. Swine in Group E showed a significant improvement in inflammation environment, liver function and hepatocyte proliferation. Levels of hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) in Group E were elevated compared to other groups. Conclusions. IL-1Ra chitosan nanoparticles showed significant liver targeting ability and controlled-release characteristics. Combined therapy with IL-1Ra chitosan nanoparticles and MCS transplantation exhibits great synergistic effects through paracrine function and suppression of inflammation. (C) 2013 IMSS. Published by Elsevier Inc.