title: [A novel treatment regimen for acute liver failure based on a combination of mesenchymal stem cells transplantation and IL-lRa-loaded chitosan nanoparticles].
abstract: OBJECTIVE
  To evaluate whether a combination therapy using allogeneic mesenchymal stem cell (MSC) transplantation and interleukin-1 receptor antagonist (IL-1Ra) chitosan nanoparticles is more robust than MSC transplantation alone for treating acute liver failure and to investigate the mechanisms of the improved therapeutic effect using a swine model system.
  
  
  METHODS
  IL-1Ra-loaded nanoparticles were made of lactosylated chitosan-FITC using the electrostatic spray method and analyzed by enzyme-linked immunosorbent assay. The active live targeting of these nanopaticles were investigated by fluorescence microscope and flow cytometer(FCM). The combined therapy was given and the Detailed Steps as follows: Chinese experimental mini swine were given D-galactosamine to build models of acute liver failure. Thirty-four pigs were randomly divided into five groups. In the control group(A),the normal saline was injected into liver via portal veins after 24 h; in IL-1Ra group(B), IL-1Ra was injected via ear veins 6 h before normal saline; In the MSCs transplantation group (C), 8 * 107 MSCs were injected into liver via portal veins after 24 h; IL-1Ra together with MSCs transplantation group(D) and nanopaticles group(E) as follows: on the one hand, 8 * 107 MSCs were injected into liver via portal veins after 24 h, on the other hand, rhIL-1Ra in group C or IL-1Ra chitosan nanopaticles in group D was injected via ear veins respectively at 6 h before. Liver function, serum inflammation and pathological changes were measured. The fate of MSCs was also observed.
  
  
  RESULTS
  The profiles in vitro shown that there was a steady-state release after a fast linear release; The live targeting of the lactosylated chitosan-based nanoparticles was achieved by ligand-receptor specificity; The biochemical assay, the serum inflammation lever and pathological changes of the nanopaticles group were all greatly different from the other groups, the hepatocytes grow rate was significantly improved after 1 week; The liver engraftment was very low in group C and D with significantly higher numbers found in nanopaticles group, but the differentiation of MSCs after 2 weeks relatively rare; western blot showed that there was more HGF and VEGF secreted in nanopaticles group.
  
  
  CONCLUSIONS
  IL-lRa-loaded lactosylated chitosan-based nanopaticles have significant liver targeting abilities and slow release characteristics in PBS solution. The combined therapy showed great synergistic effects through suppression of liver inflammation and paracrine.
authors.affiliation: Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 21008, China.
authors.forename: Jiang-Qiang
authors.initials: JQ
authors.lastname: Xiao
authors.forename: Xiao-Lei
authors.initials: XL
authors.lastname: Shi
authors.forename: Jia-Jun
authors.initials: JJ
authors.lastname: Tan
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Qian
authors.initials: Q
authors.lastname: Xu
authors.forename: Yi-Tao
authors.initials: YT
authors.lastname: Ding
mesh_terms: D048271:Chitosan; D017114:Liver Failure, Acute; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D053758:Nanoparticles
chemical_list: D048271:Chitosan