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Molecular analysis of differentiation mechanism of hMSC into hepatocyte and application to liver regeneration therapy

Research Project

Project/Area Number 18590740
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionSapporo Medical University

Principal Investigator

TAKIMOTO Rishu  Sapporo Medical University, 4th Department of Internal Medicine, Assistant Prof. (10336399)

Co-Investigator(Kenkyū-buntansha) TAKAYAMA Tetsuji  University of Tokushima, 大学院・ヘルスバイオサイエンス研究部, Prof. (10284994)
SATO Yasushi  Sapporo Medical University, 4th Department of Internal Medicine, Assistant Prof. (80343383)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordshMSC / liver / transdifferentiation
Research Abstract

Hepatic transdifferentiation of bone marrow cells has been previously demonstrated by intravenous administration of donor cells, which may recirculate to the liver after undergoing proliferation and differentiation in the recipient's bone marrow. We have recently disclosed that human mesenchymal stem cells (MSCs) could transdifferentiate into hepatocyte-like cells when directly xenografting to allylalcohol (AA)-treated rat liver (Blood 2005, 106 : 756-763). However, the efficacy of differentiation into hepatocyte-like cells was at most 0.5% of hMSC injected to rat liver. In this study, we established the immortalized hMSC transduced with hTERT gene as well as Bmi-1 in order to obtain efficient proliferation rate for large-scale preparation. As a result, hMSC-TERT-Bmi-1 clone transdifferentiated into hepatocyte-like cells which produced human albumin and P450, CYP3A4, CYP2C8 and CYP2C9. Furthermore, hepatocyte-like cells derived from hMSC-TERT-Bmi-1 clone could store glycogen and LDL, suggesting that these cells could be applied for drug metabolism, drug sensitivity and virus infection model.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (35 results)

All 2008 2007 2006

All Journal Article (35 results) (of which Peer Reviewed: 20 results)

  • [Journal Article] Resolution of liver cirrhosis using vitamin A-coupled liposomes to deliver siRNA against a collagen-specific chaperone. Nat Biotechnol2008

    • Author(s)
      Sateo Y, Takimoto R.
    • Journal Title

      Nat Biotecluiol (Epub ahead of print)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Ex vivo large-scale generation of human red blood cells from cord blood CD34(+) cells by co-culturing with macrophages2008

    • Author(s)
      Fujimi A, Takimoto R.
    • Journal Title

      Int J Hematol (Epub ahead of print)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Aberrant crypt foci as precursors of the dysplasia-carcinoma sequence in patients with ulcerative colitis2008

    • Author(s)
      Kukitsu T, Takimoto R.
    • Journal Title

      Clin Cancer Res2 14(1)

      Pages: 48-54

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Combination therapy of an anticancer drug with the FNIII14 peptide of fibronectin effectively overcomes cell adhesion-mediated drug resistance of acute myelogenous leukemia2008

    • Author(s)
      Matsunaga T, Takimoto R.
    • Journal Title

      Leukemia 22(2)

      Pages: 353-360

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Adenovira lvector-mediated transfer of the Indian hedgehog gene modelates 1lymphomyelopoiesis in vivo2008

    • Author(s)
      Kobune M, Takimoto R.
    • Journal Title

      Stem Cells 26(2)

      Pages: 534-542

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Resolution of liver cirrhosis using vitamin A-coupled liposomes to deliver siRNA against a collagen-specific chaperone2008

    • Author(s)
      Sato, Y., Takimoto, R
    • Journal Title

      Nat Biotechnol (Epub ahead of print)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Ex vivo large-scale generation of human red blood cells from cord blood CD34(+) cells by co-culturing with macrophages2008

    • Author(s)
      Fujimi, A., Takimoto, R
    • Journal Title

      Int J Hematol (Epub ahead of print)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Aberrant crypt foci as precursors of the dysplasia-carcinoma sequence in patients with ulcerative colitis2008

    • Author(s)
      Kukitsu, T., Takimoto, R
    • Journal Title

      Clin Cancer Res 1, 14(1)

      Pages: 48-54

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Combination therapy of an anticancer drug with the FNIII14 peptide of fibronectin effectively overcomes cell adhesion-mediated drug resistance of acute myelogenous leukemia2008

    • Author(s)
      Matsunaga, T., Takimoto, R
    • Journal Title

      Leukemia 22(2)

      Pages: 353-60

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Adenoviral vector-mediated transfer of the Indian hedgehog gene modulates lymphomyelopoiesis in vivo2008

    • Author(s)
      Kobune, M., Takimoto, R
    • Journal Title

      Stem Cells 26(2)

      Pages: 534-42

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Resolution of liver cirrhosis using vitamin A-coupled liposomes to deliver siRNA against a collagen-specific chaperone.2008

    • Author(s)
      Sato Y, et. al.
    • Journal Title

      Nat Biotechnol (In press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Phase I Trial of Arterial Infusion Chemotherapy with Gemcitabine and 5-Fluorouracil for Unresectable Advanced Pancreatic Cancer after Vascular Supply Distribution via Superselective Embolization.2008

    • Author(s)
      Miyanishi K, et. al.
    • Journal Title

      Jpn J Clin Oncol (In press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ex vivo large-scale generation of human red blood cells from cord blood CD34(+)cells by co-culturing with macrophages2008

    • Author(s)
      Fujimi A, et. al.
    • Journal Title

      Int J Hematol (In press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aberrant crypt foci as precursors of the dysplasia-carcinoma sequence in patients with ulcerative colitis2008

    • Author(s)
      Kukitsu T, et. al.
    • Journal Title

      Clin Cancer Res. 1;14(1)

      Pages: 48-54

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Combination therapy of an anticancer drug with the FNIII14 peptide of fibronectin effectively overcomes cell adhesion-mediated drugresistance of acute myelogenous leukemia.2008

    • Author(s)
      Matsunaga T, et. al.
    • Journal Title

      Leukemia 22(2)

      Pages: 353-360

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Wnt3/RhoA/ROCK signaling pathway is involved in adhesion-mediated drug resistance of multiple myeloma in an autocrine mechanism2007

    • Author(s)
      Kobune M, Takimoto R.
    • Journal Title

      Mol Cancer Ther 6(6)

      Pages: 1774-1784

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Iron/1RP-1-dependent regulation of mRNA expression for transferrin receptor, DMT1 and fenritin during human erythroid differentiation2007

    • Author(s)
      Kato J, Takimoto R.
    • Journal Title

      Exp Hematol 35(6)

      Pages: 879-887

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Essential role of protein kinase C zeta in transducing a motility signal in duced by superoxide and a chemotactic peptide, fMLP2007

    • Author(s)
      Kuribayashi K, Takimoto R.
    • Journal Title

      J Cell Biol 176(7)

      Pages: 1049-1060

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Wnt3/RhoA/ROCK signaling pathway is involved in adhesion-mediated drag resistance of multiple myeloma in an autocrine mechanism2007

    • Author(s)
      Kobune, M., Takimoto, R
    • Journal Title

      Mol Cancer Ther 6(6)

      Pages: 1774-84

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Iron/IRP-1-dependent regulation of mRNA expression for transferring receptor, DMT1 and ferritin during human erythroid differentiation2007

    • Author(s)
      Kato, J., Takimoto, R
    • Journal Title

      Exp Hematol 35(6)

      Pages: 879-87

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Essential role of protein kinase C zeta in transducing a motility signal induced by superoxide and a chemotactic peptide, fMLP2007

    • Author(s)
      Kuribayashi, K., Takimoto, R
    • Journal Title

      J Cell Biol 26, 176(7)

      Pages: 1049-60

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Adenoviral vector-mediated transfer of the Indian hedgehog gene modulates lymphomyelopoiesis in vivo.2007

    • Author(s)
      Kobune M, et. al.
    • Journal Title

      Stem Cells 26(2)

      Pages: 534-542

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Wnt3/RhoA/ROCK signaling pathway is involved in adhesion-mediated drug resistance of multiple myeloma in an autocrine mechanism2007

    • Author(s)
      Kobune M, et. al.
    • Journal Title

      Mol Cancer Ther 6(6)

      Pages: 1774-1784

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Iron/IRP-1-dependent regulation of mRNA expression for transferrin receptor, DMT1 and ferritin during human erythroid differentiation.2007

    • Author(s)
      Kato J, et. al.
    • Journal Title

      Exp Hematol. 35(6)

      Pages: 879-887

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Essential role of protein kinase C zeta in transducing a motility signal induced by superoxide and a chemotactic peptide, fMLP2007

    • Author(s)
      Kuribayashi K, et. al.
    • Journal Title

      J Cell Biol 26;176(7)

      Pages: 1049-1060

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hepatitis C virus core protein promotes proliferation of human hepatoma cells through enhancement of transforming growth factor alpha expression via activation of nuclear factor-kappaB2006

    • Author(s)
      Sato Y, Takimoto R.
    • Journal Title

      Gut 55(12)

      Pages: 1801-1808

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] A phase I/II study of nedaplatin and 5-fluorouracil with concurrent radiot herapy in patients with esophageal cancer2006

    • Author(s)
      Sato Y, Takimoto R.
    • Journal Title

      Cancer Chemother Pharmacol 58(5)

      Pages: 570-576

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Ex vivo expansion of G-CSF-mobilized peripheral blood CD133+ progenitor cells on coculture with human stromal cells2006

    • Author(s)
      Kawano Y, Takimoto R.
    • Journal Title

      Exp Hematol 34(2)

      Pages: 150-158

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Hepatitis C virus core protein promotes proliferation of human hepatoma cells through enhancement of transforming growth factor alpha expression via activation of nuclear factor-kappaB2006

    • Author(s)
      Sato, Y., Takimoto, R
    • Journal Title

      Gut 55(12)

      Pages: 1801-8

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] A phase I/II study of nedaplatin and 5-fluorouracil with concurrent radiotherapy in patients with esophageal cancer. Cancer Chemother Pharmacol2006

    • Author(s)
      Sato, Y., Takimoto, R
    • Journal Title

      Cancer Chemother Pharmacol 58(5)

      Pages: 570-6

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Exvivo expansion of G-CSF-mobilized peripheral blood CD133+ progenitor cells on coculture with human stromal cells2006

    • Author(s)
      Kawano, Y., Takimoto, R
    • Journal Title

      Exp Hematol 34(2)

      Pages: 150-8

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Ex vivo expansion of G-CSF-mobilized peripheral blood CD133+ progenitor cells on coculture with hunan stromal cells.2006

    • Author(s)
      Kawano Y., Takimoto R., et al.
    • Journal Title

      Exp Hematol 34(2)

      Pages: 150-158

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Hepatitis C virus core protein promotesproliferation of human hepatoma cells through enhancement of transforminggrowth factor α expression via activation of nuclear factor-kB.2006

    • Author(s)
      Sato Y, Kato J, Takimoto R, et al.
    • Journal Title

      Gut 55(12)

      Pages: 1801-1808

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A phase I/II study of nedaplatin and 5-fluorouracil with concurrent radiotherapy in patients with esophageal cancer2006

    • Author(s)
      Sato Y, Takimoto R, et al.
    • Journal Title

      Cancer Chemother Pharmacol 58(5)

      Pages: 570-576

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Ex vivo large-scale generation of human platelets from cord blood CD34+cells.2006

    • Author(s)
      Matsunaga T, Takimoto R, et al.
    • Journal Title

      Stem Cells 24(12)

      Pages: 2877-2887

    • Related Report
      2006 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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