title: Efficacy of mesenchymal stem cells in suppression of hepatocarcinorigenesis in rats: possible role of Wnt signaling.
abstract: BACKGROUND
  The present study was conducted to evaluate the tumor suppressive effects of bone marrow derived mesenchymal stem cells (MSCs) in an experimental hepatocellular carcinoma (HCC) model in rats and to investigate the possible role of Wnt signaling in hepato-carcinogenesis.
  
  
  METHODS
  Ninety rats were included in the study and were divided equally into: Control group, rats which received MSCs only, rats which received MSCs vehicle only, HCC group induced by diethylnitroseamine (DENA) and CCl(4), rats which received MSCs after HCC induction, rats which received MSCs before HCC induction. Histopathological examination and gene expression of Wnt signaling target genes by real time, reverse transcription-polymerase chain reaction (RT-PCR) in rat liver tissue, in addition to serum levels of ALT, AST and alpha fetoprotein were performed in all groups.
  
  
  RESULTS
  Histopathological examination of liver tissue from animals which received DENA-CCl(4) only, revealed the presence of anaplastic carcinoma cells and macro-regenerative nodules type II with foci of large and small cell dysplasia. Administration of MSCs into rats after induction of experimental HCC improved the histopathological picture which showed minimal liver cell damage, reversible changes, areas of cell drop out filled with stem cells. Gene expression in rat liver tissue demonstrated that MSCs downregulated β-catenin, proliferating cell nuclear antigen (PCNA), cyclin D and survivin genes expression in liver tissues after HCC induction. Amelioration of the liver status after administration of MSCs has been inferred by the significant decrease of ALT, AST and Alpha fetoprotein serum levels. Administration of MSCs before HCC induction did not show any tumor suppressive or protective effect.
  
  
  CONCLUSIONS
  Administration of MSCs in chemically induced HCC has tumor suppressive effects as evidenced by down regulation of Wnt signaling target genes concerned with antiapoptosis, mitogenesis, cell proliferation and cell cycle regulation, with subsequent amelioration of liver histopathological picture and liver function.
authors.affiliation: Unit of Biochemistry and Molecular Biology, Department of Medical Biochemistry, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Mohamed T
authors.initials: MT
authors.lastname: Abdel aziz
authors.forename: Mohamed F
authors.initials: MF
authors.lastname: El Asmar
authors.forename: Hazem M
authors.initials: HM
authors.lastname: Atta
authors.forename: Soheir
authors.initials: S
authors.lastname: Mahfouz
authors.forename: Hanan H
authors.initials: HH
authors.lastname: Fouad
authors.forename: Nagwa K
authors.initials: NK
authors.lastname: Roshdy
authors.forename: Laila A
authors.initials: LA
authors.lastname: Rashed
authors.forename: Dina
authors.initials: D
authors.lastname: Sabry
authors.forename: Amira A
authors.initials: AA
authors.lastname: Hassouna
authors.forename: Fatma M
authors.initials: FM
authors.lastname: Taha
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D056741:Cyclin D / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D008114:Liver Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D000077022:Survivin; D051153:Wnt Proteins / Q000378:metabolism*; D000509:alpha-Fetoproteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: C516989:Birc5 protein, rat; D056741:Cyclin D; D008869:Microtubule-Associated Proteins; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D000077022:Survivin; D051153:Wnt Proteins; D000509:alpha-Fetoproteins; D051176:beta Catenin