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Development of liver regeneration therapy against severe hepatic failure based on stem cell science -Differentiation and growth of hepatic stem cell and cell transplantation.

Research Project

Project/Area Number 15390224
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionYamagata University

Principal Investigator

KAWATA Sumio  Yamagata Univ., Medical Sch., Professor, 医学部, 教授 (90183285)

Co-Investigator(Kenkyū-buntansha) TOGASHI Hitoshi  Yamagata Univ., Medical Sch., Associate Professor, 医学部, 助教授 (60192209)
SAITO Takafumi  Yamagata Univ., Medical Sch., Assistant Professor, 医学部, 講師 (80250918)
SAITO Kouji  Yamagata Univ., Medical Sch., Assistant Professor, 医学部, 講師 (90250919)
渡辺 久剛  山形大学, 医学部, 助手 (00332536)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥13,600,000 (Direct Cost: ¥13,600,000)
Fiscal Year 2004: ¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 2003: ¥7,400,000 (Direct Cost: ¥7,400,000)
KeywordsLiver regeneration / Hepatic stem cells / oval cells / Musashi-1 gene / Notch signal / Matrigel / bone marrow cells / GFP transgenic mice / Musashi-1 / GFPトランスジェニック・マウス / oval cell line / Musashi-1遺伝子 / natchシグナル
Research Abstract

We are trying to develop an innovative therapy for severer hepatic failure to transplant hepatic stem cells. In this therapy, It is an important step to isolate hepatic stem cells expressing Musashi-1 gene.
In 2003 we showed that oval cells, a cell lineage of hepatic stem cells, expressed Musashi-1 gene in rat liver injury model. The expression of Musashi-1 gene in oval cells was regulated by signal transduction pathways through notch and jagged 1.
In 2004, we development of culture system using Matrigel, in which bone marrow cells could differentiated into phenotype of hepatocytes. Bone marrow cells expressed hepatocyte-specific genes such as albumin, AFP, cytokeratin 8, and tryptophan-2,3-dioxygenease. Further, the cells on Matrigel showed hepatic cord-like structure.
This study demonstrated findings as follows : 1)there exist bone marrow cell which can differentiate into hepatocyte-phenotype, 2)transplanted bone marrow cells could anchor in the liver when the liver injury was severe, 3)bpne marrow cell could effectively grow and differentiate into hepatocytes on Matrigel.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (21 results)

All 2005 2004 2003 Other

All Journal Article (15 results) Publications (6 results)

  • [Journal Article] Expression of Notch signal markers in bone marrow cells that differentiate a Liver cell lineage in a rat transplant model.2005

    • Author(s)
      Okumoto K, Kawata S, et al.
    • Journal Title

      Hepatol Res 31

      Pages: 7-12

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Enhanced expression of SOCS-1 in the liver of chronic hepatitis C.2005

    • Author(s)
      Imamura K, Kawata S, et al.
    • Journal Title

      J Viral Hepat 12

      Pages: 130-138

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of Notch signaling markers in bone marrow cell that differentiate Into a liver cell lineage in a rat transplant model.2005

    • Author(s)
      Okumoto K, Kawata S, et al.
    • Journal Title

      Hepatol Res 31

      Pages: 7-12

    • NAID

      10015455865

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Enhanced expression of SOCS-1 in the liver of chronic hepatitis C.2005

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

      J Viral Hepat 12

      Pages: 130-138

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of Notch signaling markers in bone marrow cells that differentiate into a liver cell lineage in a rat transplant model.2005

    • Author(s)
      Okumoto K, Kawata S, et al.
    • Journal Title

      Hepatol Res 31

      Pages: 7-12

    • NAID

      10015455865

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Enhanced expression of suppressor of cytokine signaling-I in the liver of chronic hepatitis C : possible involevement in resistance to interferon therapy.2005

    • Author(s)
      Imanaka K, Kawata S, et al.
    • Journal Title

      J Viral Hepat 12

      Pages: 130-138

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Genetic variation in humans associated with difference in the course of Hepatitis C.2004

    • Author(s)
      Saito T, Kawata S, et al.
    • Journal Title

      Biochem Biophys Res Commun 30

      Pages: 335-341

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Genetic variation in humans associated with differences in the course of hepatitis C.2004

    • Author(s)
      Saito T, Kawata S, et al.
    • Journal Title

      Biochem Biophys Res Commun 30

      Pages: 335-341

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Possible contribution of circulating transforming growth factor- β1 to immunity and prognosis in unresectable hepatocellular carcinoma.2004

    • Author(s)
      Okumoto K, Kawata S, et al.
    • Journal Title

      Liver International 24

      Pages: 21-28

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Interferon treatment improves survival in chronic hepatitis C patients showing biochemical as well as virological responses by preventing liver-related death.2004

    • Author(s)
      Kasahara A, Kawata S, et al.
    • Journal Title

      J Viral Hepat 11

      Pages: 148-156

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Transmission of hepatitis C virus quasispeces between human adults.2004

    • Author(s)
      Saito T, Kawata S, et al.
    • Journal Title

      Hepatol Res 30

      Pages: 57-62

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Differentiation of bone marrow cells into cells that express liver-specific genes Invitro.a a2003

    • Author(s)
      Okumoto K, Kawata S, et al.
    • Journal Title

      Biochem Biophys Res Commun 304

      Pages: 691-695

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Liver regeneration in HB-EGF transgenic mice after partial hepatectomy.2003

    • Author(s)
      Kiso S, Kawata S, et al.
    • Journal Title

      Gastroenterology 124

      Pages: 701-707

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Separate of ASGR in the right and left hepatic lobe using 99Tc-GSA SPECT.2003

    • Author(s)
      Sugahara K, Kawata S, et al.
    • Journal Title

      Hepatology 38

      Pages: 1401-1409

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Differentiation of bone marrow cells into cells that express liver-specific genes In vitro.2003

    • Author(s)
      Okumoto K, Kawata S, et al.
    • Journal Title

      Biochem Biophys Res Commun 304

      Pages: 691-695

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Kiso S, Kawata S, et al.: "Liver regeneration in HB-EGF transgenic mice after partial hepatectuny"Gastroenterology. 124. 701-707 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Okumoto K, Kawata S, et al.: "Differentiation of bone marrow cells into cells that express liver-specific genes in vitro"Biochem.Biophys Res Commun.. 304. 691-695 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Watanabe H, Saito T, et al.: "Spontaneous elimination of serum HCT RNA in chronic HCV carriers"J.Med Virol. 71. 56-61 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ogata S, Kawata S, et al.: "Identification of HCV style 16 strains associated with HCC"J.Clin Microbiol. 41. 2835-2841 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sugahara K, Kawata S, et al.: "Separate of ASGR in the right and left hepatic lobe using ^<99>TC-GSA SPECT"Hepatology. 38. 1401-1409 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hattori E, Kawata S, et al.: "Possible contribution of circulating IL-10 to prognosis in patients with HCC"Hepatology Res. 27. 309-314 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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