title: Transplanted human amniotic membrane-derived mesenchymal stem cells ameliorate carbon tetrachloride-induced liver cirrhosis in mouse.
abstract: BACKGROUND
  Human amniotic membrane-derived mesenchymal stem cells (hAMCs) have the potential to reduce heart and lung fibrosis, but whether could reduce liver fibrosis remains largely unknown.
  
  
  RESULTS
  Hepatic cirrhosis model was established by infusion of CCl₄ (1 ml/kg body weight twice a week for 8 weeks) in immunocompetent C57Bl/6J mice. hAMCs, isolated from term delivered placenta, were infused into the spleen at 4 weeks after mice were challenged with CCl₄. Control mice received only saline infusion. Animals were sacrificed at 4 weeks post-transplantation. Blood analysis was performed to evaluate alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Histological analysis of the livers for fibrosis, hepatic stellate cells activation, hepatocyte apoptosis, proliferation and senescence were performed. The donor cell engraftment was assessed using immunofluorescence and polymerase chain reaction. The areas of hepatic fibrosis were reduced (6.2%±2.1 vs. control 9.6%±1.7, p<0.05) and liver function parameters (ALT 539.6±545.1 U/dl, AST 589.7±342.8 U/dl,vs. control ALT 139.1±138.3 U/dl, p<0.05 and AST 212.3±110.7 U/dl, p<0.01) were markedly ameliorated in the hAMCs group compared to control group. The transplantation of hAMCs into liver-fibrotic mice suppressed activation of hepatic stellate cells, decreased hepatocyte apoptosis and promoted liver regeneration. More interesting, hepatocyte senescence was depressed significantly in hAMCs group compared to control group. Immunofluorescence and polymerase chain reaction revealed that hAMCs engraftment into host livers and expressed the hepatocyte-specific markers, human albumin and α-fetoproteinran.
  
  
  CONCLUSIONS
  The transplantation of hAMCs significantly decreased the fibrosis formation and progression of CCl₄-induced cirrhosis, providing a new approach for the treatment of fibrotic liver disease.
authors.affiliation: The Research Center for Bone and Stem Cells, Nanjing Medical University, Nanjing, China.
authors.forename: DingGuo
authors.initials: D
authors.lastname: Zhang
authors.forename: MinYue
authors.initials: M
authors.lastname: Jiang
authors.forename: DengShun
authors.initials: D
authors.lastname: Miao
mesh_terms: D000650:Amnion / Q000166:cytology*; D000818:Animals; D002251:Carbon Tetrachloride; D002252:Carbon Tetrachloride Poisoning / Q000473:pathology / Q000628:therapy*; D002478:Cells, Cultured; D005260:Female; D022781:Hepatocytes / Q000473:pathology / Q000502:physiology; D006801:Humans; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D008115:Liver Regeneration / Q000502:physiology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D002251:Carbon Tetrachloride