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Efficacy of mesenchymal stem cells in suppression of hepatocarcinorigenesis in rats: possible role of Wnt signaling.

Abdel aziz MT, El Asmar MF, Atta HM, Mahfouz S, Fouad HH, Roshdy NK, Rashed LA, Sabry D, Hassouna AA, Taha FM - J. Exp. Clin. Cancer Res. (2011)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Unit of Biochemistry and Molecular Biology, Department of Medical Biochemistry, Faculty of Medicine, Cairo University, Cairo, Egypt.

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.

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Related in: MedlinePlus

Agrose gel electrophoresis for Molecular identification of undifferentiated and differentiated BM-MSCs: (A) gene expression of osteonectin (B) gene expression of collagen II and (C) gene expression of GAPDH in undifferentiated and differentiated MSCs. (A&B) Genes expression of osteonectin and collagen II. Lane 1: DNA marker (100, 200, 300 bp). Lane 2:No PCR product for osteonectin and Collagen II genes in undifferentiated MSCs. Lane 3: PCR product for osteonectin and Collagen II genes in differentiated MSCs (C) Gene expression of GAPDH. Lane 1: DNA marker (100, 200, 300 bp). Lane 2: PCR product for GAPDH gene in undifferentiated MSCs
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Figure 4: Agrose gel electrophoresis for Molecular identification of undifferentiated and differentiated BM-MSCs: (A) gene expression of osteonectin (B) gene expression of collagen II and (C) gene expression of GAPDH in undifferentiated and differentiated MSCs. (A&B) Genes expression of osteonectin and collagen II. Lane 1: DNA marker (100, 200, 300 bp). Lane 2:No PCR product for osteonectin and Collagen II genes in undifferentiated MSCs. Lane 3: PCR product for osteonectin and Collagen II genes in differentiated MSCs (C) Gene expression of GAPDH. Lane 1: DNA marker (100, 200, 300 bp). Lane 2: PCR product for GAPDH gene in undifferentiated MSCs

Mentions: Isolated and cultured undifferentiated MSCs reached 70-80% confluence at 14 days (Figure 1). In vitro osteogenic and chondrogenic differentiation of MSCs were confirmed by morphological changes and special stains (Figure 2a,b and Figure 3a,b respectively) in addition to gene expression of osteonectin and collagen II (Figure 4a&4b) and GADPH (Figure 4c).


Efficacy of mesenchymal stem cells in suppression of hepatocarcinorigenesis in rats: possible role of Wnt signaling.

Abdel aziz MT, El Asmar MF, Atta HM, Mahfouz S, Fouad HH, Roshdy NK, Rashed LA, Sabry D, Hassouna AA, Taha FM - J. Exp. Clin. Cancer Res. (2011)

Agrose gel electrophoresis for Molecular identification of undifferentiated and differentiated BM-MSCs: (A) gene expression of osteonectin (B) gene expression of collagen II and (C) gene expression of GAPDH in undifferentiated and differentiated MSCs. (A&B) Genes expression of osteonectin and collagen II. Lane 1: DNA marker (100, 200, 300 bp). Lane 2:No PCR product for osteonectin and Collagen II genes in undifferentiated MSCs. Lane 3: PCR product for osteonectin and Collagen II genes in differentiated MSCs (C) Gene expression of GAPDH. Lane 1: DNA marker (100, 200, 300 bp). Lane 2: PCR product for GAPDH gene in undifferentiated MSCs
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3113743&req=5

Figure 4: Agrose gel electrophoresis for Molecular identification of undifferentiated and differentiated BM-MSCs: (A) gene expression of osteonectin (B) gene expression of collagen II and (C) gene expression of GAPDH in undifferentiated and differentiated MSCs. (A&B) Genes expression of osteonectin and collagen II. Lane 1: DNA marker (100, 200, 300 bp). Lane 2:No PCR product for osteonectin and Collagen II genes in undifferentiated MSCs. Lane 3: PCR product for osteonectin and Collagen II genes in differentiated MSCs (C) Gene expression of GAPDH. Lane 1: DNA marker (100, 200, 300 bp). Lane 2: PCR product for GAPDH gene in undifferentiated MSCs
Mentions: Isolated and cultured undifferentiated MSCs reached 70-80% confluence at 14 days (Figure 1). In vitro osteogenic and chondrogenic differentiation of MSCs were confirmed by morphological changes and special stains (Figure 2a,b and Figure 3a,b respectively) in addition to gene expression of osteonectin and collagen II (Figure 4a&4b) and GADPH (Figure 4c).

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Unit of Biochemistry and Molecular Biology, Department of Medical Biochemistry, Faculty of Medicine, Cairo University, Cairo, Egypt.

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.

Show MeSH
Related in: MedlinePlus