title: Bone marrow-derived mesenchymal stem cells ameliorate hepatic ischemia reperfusion injury in a rat model.
abstract: BACKGROUND
  Ischemia-reperfusion (I/R) injury associated with living donor liver transplantation impairs liver graft regeneration. Mesenchymal stem cells (MSCs) are potential cell therapeutic targets for liver disease. In this study, we demonstrate the impact of MSCs against hepatic I/R injury and hepatectomy.
  
  
  RESULTS
  We used a new rat model in which major hepatectomy with I/R injury was performed. Male Lewis rats were separated into two groups: an MSC group given MSCs after reperfusion as treatment, and a Control group given phosphate-buffered saline after reperfusion as placebo. The results of liver function tests, pathologic changes in the liver, and the remnant liver regeneration rate were assessed. The fate of transplanted MSCs in the luciferase-expressing rats was examined by in vivo luminescent imaging. The MSC group showed peak luciferase activity of transplanted MSCs in the remnant liver 24 h after reperfusion, after which luciferase activity gradually declined. The elevation of serum alanine transaminase levels was significantly reduced by MSC injection. Histopathological findings showed that vacuolar change was lower in the MSC group compared to the Control group. In addition, a significantly lower percentage of TUNEL-positive cells was observed in the MSC group compared with the controls. Remnant liver regeneration rate was accelerated in the MSC group.
  
  
  CONCLUSIONS
  These data suggest that MSC transplantation provides trophic support to the I/R-injured liver by inhibiting hepatocellular apoptosis and by stimulating regeneration.
authors.affiliation: Division of Development of Advanced Treatment, Center for Development of Advanced Medical Technology, Jichi Medical University, Yakushiji City, Tochigi, Japan. kagoshimakurobuta@hotmail.com
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kanazawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujimoto
authors.forename: Takumi
authors.initials: T
authors.lastname: Teratani
authors.forename: Junji
authors.initials: J
authors.lastname: Iwasaki
authors.forename: Naoya
authors.initials: N
authors.lastname: Kasahara
authors.forename: Kouji
authors.initials: K
authors.lastname: Negishi
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Tsuruyama
authors.forename: Shinji
authors.initials: S
authors.lastname: Uemoto
authors.forename: Eiji
authors.initials: E
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001854:Bone Marrow Cells / Q000166:cytology*; D019070:Cell Lineage; D004195:Disease Models, Animal; D007249:Inflammation; D008099:Liver / Q000473:pathology*; D008107:Liver Diseases / Q000628:therapy*; D008115:Liver Regeneration; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000473:pathology* / Q000628:therapy*