title: Administration of IL-1Ra chitosan nanoparticles enhances the therapeutic efficacy of mesenchymal stem cell transplantation in acute liver failure.
abstract: OBJECTIVE
  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 × 10⁷ 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.
authors.affiliation: Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China; Jiangsu Province Key Medical Center for Hepatobiliary Disease, Nanjing, China.
authors.forename: Jiang-qiang
authors.initials: JQ
authors.lastname: Xiao
authors.forename: Xiao-lei
authors.initials: XL
authors.lastname: Shi
authors.forename: Hu-cheng
authors.initials: HC
authors.lastname: Ma
authors.forename: Jia-jun
authors.initials: JJ
authors.lastname: Tan
authors.lastname: Lin-zhang
authors.forename: Qian
authors.initials: Q
authors.lastname: Xu
authors.forename: Yi-tao
authors.initials: YT
authors.lastname: Ding
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D048271:Chitosan / Q000008:administration & dosage*; D016207:Cytokines / Q000378:metabolism; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000008:administration & dosage; D004357:Drug Synergism; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage*; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage*; D011897:Random Allocation; D013552:Swine
chemical_list: D016207:Cytokines; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D053590:Interleukin 1 Receptor Antagonist Protein; D048271:Chitosan
keywords: Acute liver failure; Cell transplantation; Chitosan nanoparticles; IL-1Ra; Mesenchymal stem cells