title: Autologous bone marrow stem cell transplantation attenuates hepatocyte apoptosis in a rat model of ex vivo liver resection and liver autotransplantation.
abstract: BACKGROUND
  To investigate the efficacy of autologous bone marrow stem cell (BMSC) transplantation in the treatment of hepatic injury in ex vivo liver resection and liver autotransplantation (ELRLA).
  
  
  METHODS
  Rat hepatic fibrosis was induced by intraperitoneal injection of 50% CCl4-olive oil solution at a dose of 2 mL/kg twice weekly for 4 wk. ELRLA was performed 3 d post the last injection of CCl4. Six rats in each group were killed 12, 24, 48, 72, and 168 h after the operation. Hepatocyte apoptosis was determined by TUNEL assay. The expression of Bcl-2, Bax, transforming growth factor (TGF) β1, TGFβ1 receptor1/2, and phosphorylated p38 MAPK were determined by Western blot.
  
  
  RESULTS
  Autologous BMSC transplantation significantly inhibited the increase of alanine aminotransferease and aspartate aminotransferase at 12, 24, and 48 h post operation and attenuated ELRLA-induced hepatocyte apoptosis. In BMSC-treated rats, the expression of Bcl-2 was significantly upregulated, whereas there were no obvious changes in Bax level. The expression of TGFβ1 was significantly upregulated in the rat liver after the surgery. Autologous BMSC transplantation significantly downregulated the TGFβ1 levels at 48, 72, and 168 h post surgery. However, autologous BMSC transplantation showed little effect on the levels of TGFβ receptor 1/2 at all the time points observed. Furthermore, autologous BMSC transplantation significantly inhibited the activation of p38 MAPK.
  
  
  CONCLUSIONS
  Autologous BMSC transplantation may reduce ELRLA-induced liver injury and improve survival rates in hepatic fibrosis rats. Autologous BMSC transplantation may be useful to improve the outcome of patients who undergo ELRLA.
authors.affiliation: Department of Hepatobiliary Surgery, Institute of Hepatobiliary Surgery of PLA, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Tubing
authors.initials: T
authors.lastname: Xu
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Wang
authors.forename: Geng
authors.initials: G
authors.lastname: Chen
authors.forename: Yu
authors.initials: Y
authors.lastname: He
authors.forename: Ping
authors.initials: P
authors.lastname: Bie
mesh_terms: D000818:Animals; D017209:Apoptosis; D016026:Bone Marrow Transplantation / Q000379:methods*; D002251:Carbon Tetrachloride / Q000009:adverse effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D022781:Hepatocytes / Q000473:pathology*; D008099:Liver / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000503:physiopathology / Q000601:surgery; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D033581:Stem Cell Transplantation / Q000379:methods*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014182:Transplantation, Autologous; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D053773:Transforming Growth Factor beta1; D002251:Carbon Tetrachloride; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Autologous; Bone marrow stem cell; Ex vivo liver resection and liver autotransplantation; Liver injury