title: 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.
  
  
  OBJECTIVE
  To assess the effect of IL-1? siRNA adenovirus on MSC and the therapeutic effect of MSC combined with IL-1? siRNA adenovirus in ALF.
  
  
  METHODS
  We implanted MSC or/and IL-1? 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-1?, IL-10, IL-6, VEGF and HGF), animal survival and vital MSC were assessed after cell transplantation.
  
  
  RESULTS
  MSC combined with IL-1? siRNA reduced the inflammatory levels and prevented liver failure. These animals administrated with MSC and IL-1? siRNA also exhibited improved liver regeneration and increased survival rates. Immunohistochemistry and fluorescence microscopy revealed the number of vital MSC in ALF + MSC + IL-1? siRNA group were significantly more than that in ALF + MSC group.
  
  
  CONCLUSIONS
  IL-1? siRNA adenovirus could enhance MSC ability of tissue regeneration through increasing its survival rate. Accordingly, combination of IL-1? siRNA adenovirus and MSC had a synergistic effect on acute liver failure.
authors: Department of Hepatobiliary Surgery, Affiliated DrumTower Hospital of Nanjing University Medical School, Jiangsu Province, China.
authors: Hucheng
authors: H
authors: Ma
authors: Department of Hepatobiliary Surgery, Affiliated DrumTower Hospital of Nanjing University Medical School, Jiangsu Province, China.
authors: Xiaolei
authors: X
authors: Shi
authors: Department of Hepatobiliary Surgery, Affiliated DrumTower Hospital of Nanjing University Medical School, Jiangsu Province, China.
authors: Xianwen
authors: X
authors: Yuan
authors: Department of Hepatobiliary Surgery, Affiliated DrumTower Hospital of Nanjing University Medical School, Jiangsu Province, China.
authors: Yitao
authors: Y
authors: Ding
mesh_terms: D000256:Adenoviridae; D000818:Animals; D054360:Chemokine CXCL1 / Q000187:drug effects / Q000276:immunology; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D007249:Inflammation; D016753:Interleukin-10 / Q000276:immunology; D053583:Interleukin-1beta / Q000187:drug effects*; D015850:Interleukin-6 / Q000276:immunology; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D017114:Liver Failure, Acute; D008115:Liver Regeneration / Q000187:drug effects* / Q000276:immunology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D034741:RNA, Small Interfering / Q000494:pharmacology*; D000067492:RNAi Therapeutics; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects / Q000378:metabolism
chemical_list: D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; C553307:HGF protein, mouse; C556062:IL10 protein, mouse; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D015850:Interleukin-6; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; C577686:interleukin-6, mouse; C467480:vascular endothelial growth factor A, mouse; D016753:Interleukin-10; D017228:Hepatocyte Growth Factor