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Analysis of the serum factor which promotes the repopulation and differentiation of the bone marrow cell into hepatocyte.

Research Project

Project/Area Number 16390211
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

OKITA Kiwamu  Yamaguchi University, Professor emeritus, 名誉教授 (70107738)

Co-Investigator(Kenkyū-buntansha) SAKAIDA Isao  Yamaguchi University, Graduated School of Medicine, Professor, 大学院医学系研究科, 教授 (80263763)
TERAI Shuji  Yamaguchi University, Graduated School of Medicine, Assistant Professor, 大学院医学系研究科, 講師 (00332809)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2006: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2005: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2004: ¥5,900,000 (Direct Cost: ¥5,900,000)
KeywordsGFP / CCl4 / Proteomics / Apolipo protein / FGF / HHM / BioPlex / 骨髄細胞 / 肝再生 / 血清因子 / DEP / CC14 model / CCl4 model
Research Abstract

We developed the GFP/CC14 model to evaluate the differentiation of bone marrow cell into hepatocyte. We found that bone marrow cell (BMC) were repopulated into the damaged liver and differentiated into albumin-producing hepatocyte In this condition, liver fibrosis was also significantly improved and survival rate was improved by BMC infusion. Depend on these results, we started the clinical study : Autologous BMC infusion therapy for liver cirrhosis patients (Stem Cells 2006). Here we did the proteomics analysis to find serum factor that promote repopulation and differentiation of BMC into hepatocyte. Apolipoprotein was increased significantly in the serum after BMC infusion. We also analyzed which growth factors regulate the repopulation and differentiation of BMC. We found that FGF2 was important growth factor to repopulate and differentiation of BMC into hepatocyte. On the other hands, we also examine the mechanism of the differentiation of liver stem cell. Previously we also cloned Human Homologue of Maid as a regulator of differentiation of hepatic stem cell. In this study, we started to make the Maid KO mouse to analyze how Maid regulate the differentiation of BMC into hepatocyte.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (47 results)

All 2007 2006 2005 2004

All Journal Article (43 results) Book (3 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Administration of fibroblast growth factor 2 in combination with bone marrow transplantation synergistically improves carbon tetrachloride-induced liver fibrosis in mice.2007

    • Author(s)
      Ishikawa T
    • Journal Title

      Cell Tissue Res. 327・3

      Pages: 463-470

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Administration of fibroblast growth factor 2 in combination with bone marrow transplantation synergistically improves carbon-tetrachloride-induced liver fibrosis in mice.2007

    • Author(s)
      Ishikawa T
    • Journal Title

      Cell Tissue Res. 327(3)

      Pages: 463-70

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Clinical application of bone marrow cell transplantation for liver diseases.2006

    • Author(s)
      Sakaida I
    • Journal Title

      J Gastroenterol 41(1)

      Pages: 93-94

    • NAID

      10017328609

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Fibroblast growth factor 2 facilitates the differentiation of transplanted bone marrow cells into hepatocytes.2006

    • Author(s)
      Ishikawa T
    • Journal Title

      Cell Tissue Res. 323・2

      Pages: 221-231

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Protein level of apolipoprotein E increased in human hepatocellular carcinoma.2006

    • Author(s)
      Yokoyama Y
    • Journal Title

      Int J Oncol. 28・3

      Pages: 625-631

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Proteomic analysis of serum marker proteins in recipient mice with liver cirrhosis after bone marrow cell transplantation.2006

    • Author(s)
      Yokoyama Y
    • Journal Title

      Proteomics. 6・8

      Pages: 2564-2570

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Improved liver function in liver cirrhosis patients after autologous bone marrow cell infusion therapy2006

    • Author(s)
      Terai S
    • Journal Title

      Stem Cells 24・10

      Pages: 2292-2298

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Elevated levels of circulating cell-free DNA in the blood of patients with hepatitis C virus-associated hepatocellular carcinoma.2006

    • Author(s)
      Iizuka N
    • Journal Title

      Anticancer Res. 26・6c

      Pages: 4713-4719

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Clinical application of bone marrow cell transplantation for liver diseases.2006

    • Author(s)
      Sakaida I
    • Journal Title

      J Gastroenterol. 41(1)

      Pages: 93-4

    • NAID

      10017328609

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Protein level of apolipoprotein E increased in human hepatocellular carcinoma.2006

    • Author(s)
      Yokoyama Y
    • Journal Title

      Int J Oncol. 28(3)

      Pages: 625-31

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Proteomic analysis of serum marker proteins in recipient mice with liver cirrhosis after bone marrow cell transplantation.2006

    • Author(s)
      Yokoyama Y
    • Journal Title

      Proteomics 6(8)

      Pages: 2564-70

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Fibroblast growth factor 2 facilitates the differentiation of transplanted bone marrow cells into hepatocytes.2006

    • Author(s)
      Ishikawa T
    • Journal Title

      Cell Tissue Res 323(2)

      Pages: 221-31

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Improved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy.2006

    • Author(s)
      Terai S
    • Journal Title

      Stem Cells 24(10)

      Pages: 2292-8

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Elevated levels of circulating cell-free DNA in the blood of patients with hepatitis C virus-associated hepatocellular carcinoma.2006

    • Author(s)
      Iizuka N,.
    • Journal Title

      Anticancer Res. 26(6C)

      Pages: 4713-9

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 多施設臨床研究:肝硬変症に対するABMI療法の開発2006

    • Author(s)
      寺井 崇二
    • Journal Title

      日本再生医療学会誌、再生医療 5

      Pages: 79-87

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Proteomic analysis of serum marker proteins in recipient mice with liver cirrhosis after bone marrow cell transplantation.2006

    • Author(s)
      Yokoyama Y
    • Journal Title

      Proteomics. (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Fibroblast growth factor 2 facilitate the differentiation of transplanted bone marrow cells into hepatocytes.2006

    • Author(s)
      Ishikawa T
    • Journal Title

      Cell Tissue Res. 323(2)

      Pages: 221-231

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Development of cell therapy using autologous bone marrow cells for liver cirrhosis.2005

    • Author(s)
      Sakaida I
    • Journal Title

      Med Mol Morphol 38(4)

      Pages: 197-202

    • NAID

      10018373531

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The role of oxidative stress in NASH and fatty liver model.2005

    • Author(s)
      Sakaida I
    • Journal Title

      Hepatol Res 33

      Pages: 128-131

    • NAID

      10016809224

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] D-Penicillamineimproved laparoscopic and histological findings of the liver in a patient withWilson's disease : 3-year follow-up after diagnosis of Coombs-negative hemolytic anemia of Wilson's disease.2005

    • Author(s)
      Sakaida I
    • Journal Title

      J Gastroenterol 40(6)

      Pages: 646-651

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cytochrome c is a possible new marker for fulminant hepatitis in humans.2005

    • Author(s)
      Sakaida I
    • Journal Title

      J Gastroenterol 40(2)

      Pages: 179-185

    • NAID

      10014513692

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Use of bone marrow cells for the development of cellular therapy in liver diseases.2005

    • Author(s)
      Sakaida I
    • Journal Title

      Hepatology Res 31

      Pages: 195-196

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Leptin enhances TNF-alpha production via p38 and JNK MAPK in LPS-stimulated Kupffer cells.2005

    • Author(s)
      Shen J
    • Journal Title

      Life Sci 77(13)

      Pages: 1502-1515

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Herbal medicine Rhei rhizome prevents liver fibrosis in rat liver cirrhosis induced by acholine-deficient L-amino acid-defined diet.2005

    • Author(s)
      Jin H
    • Journal Title

      Life Sci 76(24)

      Pages: 2805-2816

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Human homologue of maid is a useful marker protein in hepatocarcinogenesis.2005

    • Author(s)
      Takami T
    • Journal Title

      Gastroenterology 128(5)

      Pages: 1369-1380

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Translational Research Project : the development of the cell therapy using autolougous bone marrow cells in liver cirrhosis patients.2005

    • Author(s)
      Terai S
    • Journal Title

      J Hepatobiliary Pancreat Surg 12(3)

      Pages: 203-207

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] D-Penicillamineimproved laparoscopic and histological findings of the liver in a patient with Wilson's disease : 3-year follow-up after diagnosis of Coombs-negative hemolytic anemia of Wilson's disease.2005

    • Author(s)
      Sakaida I
    • Journal Title

      J Gastroenterol 40(6)

      Pages: 646-51

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Herbal medicine Rhei rhizome prevents liver fibrosis in rat liver cirrhosis induced by a choline-deficient L-amino acid-defined diet.2005

    • Author(s)
      Jin H
    • Journal Title

      Life Sci 76(24)

      Pages: 2805-16

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Development of cell therapy using autologous bone marrow cells for liver cirrhosis.2005

    • Author(s)
      Sakaida I
    • Journal Title

      Med Mol Morphol. 38(4)

      Pages: 197-202

    • NAID

      10018373531

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Lesson from the GFP/CC14 model--translational research project : the development of cell therapy using autologous bone marrow cells in patients with liver cirrhosis.2005

    • Author(s)
      Terai S
    • Journal Title

      J Hepatobiliary Pancreat Surg. 12(3)

      Pages: 203-207

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Lesson from the GFP/CCl4 model-Translational Research Project : The development of the cell therapy using autolougous bone marrow cells in liver cirrhosis patients.2005

    • Author(s)
      Terai S
    • Journal Title

      J Hepatobiliary Pancreat Surg. (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Human Homologue of Maid is a useful marker protein in hepatocarcinogenesis.2005

    • Author(s)
      Takami T
    • Journal Title

      Gastroenterology (in Press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 骨髄幹細胞移植による肝疾患の治療2005

    • Author(s)
      沖田 極
    • Journal Title

      日本内科学会誌 (in press)

    • NAID

      10016636976

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Transplantation of bone marrow cells reduces CCL4-induced liver fibrosis in mice.2004

    • Author(s)
      Sakaida I
    • Journal Title

      Hepatology 40

      Pages: 1304-1311

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Acute iron intoxication.2004

    • Author(s)
      Sakaida I
    • Journal Title

      Vet Hum Toxicol 46

      Pages: 158-159

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Late evening snack and the change of blood glucose level in patients with liver cirrhosis.2004

    • Author(s)
      Sakaida I
    • Journal Title

      HEPATOL RES 30

      Pages: 67-72

    • NAID

      10015455652

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Molecular signature associated with plasticity of bone marrow cell under persistent liver damage by self-organizing-map-based gene expression.2004

    • Author(s)
      Omori K
    • Journal Title

      FEBS letters 578

      Pages: 10-20

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Proteomic profiling of proteins decreased in hepatocellular carcinoma from patients infected with hepatitis C virus2004

    • Author(s)
      Yokoyama Y
    • Journal Title

      Proteomics 6・7

      Pages: 2111-2116

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Late evening snack and the change of blood glucose level in patients with live] cirrhosis.2004

    • Author(s)
      Sakaida I
    • Journal Title

      HEPATOL RES Volume 30

      Pages: 67-72

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Proteomic profiling of proteins decreased in hepatocellular carcinoma from patients infected with hepatitis C virus2004

    • Author(s)
      Yokoyama Y
    • Journal Title

      Proteomics 6 : 7

      Pages: 2111-2116

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Transplantation of bone marrow cells reduces CCl4-induced liver fibrosis in mice.2004

    • Author(s)
      Sakaida I
    • Journal Title

      Hepatology 40(6)

      Pages: 1304-1311

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Molecular signature associated with plasticity of bone marrow cell under persistent liver damage by self-organizing-map-based gene expression.2004

    • Author(s)
      Omori K
    • Journal Title

      FEBS Lett. 578(1-2)

      Pages: 10-20

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A subpopulation of bone marrow cells depleted by a novel antibody, anti-Liv8, is useful for cell therapy to repair damaged liver.2004

    • Author(s)
      Yamamoto N
    • Journal Title

      Biochem Biophys Res Commun. 313(4)

      Pages: 1110-1118

    • Related Report
      2004 Annual Research Report
  • [Book] 肝幹細胞の分化を制御するhuman homologue of Maid (HHM)の視点から考えた肝発癌制御機構についてSurgery Frontier2007

    • Author(s)
      寺井 崇二
    • Publisher
      メデイカルレビュー社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Book] 自己骨髄細胞を用いた肝臓再生療法の開発-基礎研究から臨床研究へ 実験医学2006

    • Author(s)
      石川 剛
    • Publisher
      羊土社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] 自己骨髄細胞を用いた肝臓再生療法の開発 -基礎研究から臨床研究へ 実験医学2006

    • Author(s)
      石川 剛
    • Publisher
      羊土社
    • Related Report
      2006 Annual Research Report
  • [Patent(Industrial Property Rights)] 新規肝細胞癌の腫瘍マーカー抗HHMIgGの発見2004

    • Inventor(s)
      寺井 崇二
    • Industrial Property Rights Holder
      山口TLO
    • Filing Date
      2004-09-14
    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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