title: Effect of bone marrow-derived mesenchymal stromal cells on hepatoma.
abstract: OBJECTIVE
  The aim of the study was to evaluate the effect of mesenchymal stromal cells (MSCs) on tumor cell growth in vitro and in vivo and to elucidate the apoptotic and anti-proliferative mechanisms of MSCs on a hepatocellular carcinoma (HCC) murine model.
  
  
  METHODS
  The growth-inhibitory effect of MSCs on the Hepa 1-6 cell line was tested by means of methyl thiazolyl diphenyl-tetrazolium assay. Eighty female mice were randomized into four groups: group 1 consisted of 20 mice that received MSCs only by intrahepatic injection; group 2 consisted of 20 HCC mice induced by inoculation of Hepa 1-6 cells into livers without MSC treatment; group 3 consisted of 20 mice that received MSCs after induction of liver cancer; group 4 consisted of 20 mice that received MSCs after induction of liver cancer on top of induced biliary cirrhosis.
  
  
  RESULTS
  MSCs exhibited a growth-inhibitory effect on Hepa 1-6 murine cell line in vitro. Concerning in vivo study, decreases of serum alanine transaminase, aspartate transaminase and albumin levels after MSC transplantation in groups 2 and 3 were found. Gene expression of α-fetoprotein was significantly downregulated after MSC injection in the HCC groups. We found that gene expression of caspase 3, P21 and P53 was significantly upregulated, whereas gene expression of Bcl-2 and survivin was downregulated in the HCC groups after MSC injection. Liver specimens of the HCC groups confirmed the presence of dysplasia. The histopathological picture was improved after administration of MSCs to groups 2 and 3.
  
  
  CONCLUSIONS
  MSCs upregulated genes that help apoptosis and downregulated genes that reduce apoptosis. Therefore, MSCs could inhibit cell division of HCC and potentiate their death.
authors.affiliation: Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
authors.forename: Somia H
authors.initials: SH
authors.lastname: Abd-Allah
authors.affiliation: Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
authors.forename: Sally M
authors.initials: SM
authors.lastname: Shalaby
authors.affiliation: Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt. Electronic address: amalelshal@yahoo.com.
authors.forename: Amal S
authors.initials: AS
authors.lastname: El-Shal
authors.affiliation: Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
authors.forename: Eman Abd
authors.initials: EA
authors.lastname: Elkader
authors.affiliation: Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
authors.forename: Samia
authors.initials: S
authors.lastname: Hussein
authors.affiliation: Internal Medicine Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
authors.forename: Emad
authors.initials: E
authors.lastname: Emam
authors.affiliation: Histology and Cell Biology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
authors.forename: Nehad F
authors.initials: NF
authors.lastname: Mazen
authors.affiliation: Pathology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
authors.forename: Mohammed
authors.initials: M
authors.lastname: El Kateb
authors.affiliation: Clinical Pathology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
authors.forename: Mha
authors.initials: M
authors.lastname: Atfy
mesh_terms: D000818:Animals; D017209:Apoptosis; D063646:Carcinogenesis; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000628:therapy*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D048708:Cell Growth Processes; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D053148:Caspase 3
keywords: MSCs; apoptosis; gene expression; hepatocellular carcinoma