• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2011 Fiscal Year Final Research Report

Basic research for the production of human hepatocytes and the transplantation of hepatic tissues

Research Project

  • PDF
Project/Area Number 21390365
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

MITAKA Toshihiro  札幌医科大学, 医学部, 教授 (50231618)

Co-Investigator(Kenkyū-buntansha) TANIMIZU Naoki  札幌医科大学, 医学部, 講師 (00333386)
OOE Hidekazu  札幌医科大学, 医学部, 助教 (90452979)
ICHINOHE Norihisa  札幌医科大学, 医学部, 研究員 (80452978)
MIZUGUCHI Toru  札幌医科大学, 医学部, 准教授 (30347174)
HIRATA Koichi  札幌医科大学, 医学部, 教授 (50136959)
KIKKAWA Yamato  東京薬科大学, 薬学部, 准教授 (20274227)
TANISHITA Kazuo  慶應義塾大学, 理工学部, 教授 (10101776)
Project Period (FY) 2009 – 2011
Keywords肝再生 / 肝幹・前駆細胞 / 細胞移植 / 増殖 / 分化 / 肝組織形成 / 肝発生 / 人工肝臓
Research Abstract

We aimed to develop the methods of producing a large number of small hepatocytes(SHs), hepatic progenitor cells, and to establish the methods of hepatic organoid formation in vitro. In addition, we examined how cells and tissues could be transplanted into liver. Unlike mature hepatocytes the growth of rat SHs was regulated by Follistatin/Activin system. Although oval cells, hepatic stem cells, differentiated into hepatocytes via SHs, they could not completely mature. The transplanted hepatic stem/progenitor cells could not survive for a long term in the recipient liver and disappeared by cellular senescence. Thus, the role of hepatic stem/progenitor cells in severe liver failure may be to compensate for the lost hepatic functions transiently. To use the model of hepatic sinusoids constituting rat SHs, stellate cells, and endothelial cells, we clarified that quiescent stellate cells might regulate the capillary formation of endothelial cells and maturation of SHs.

  • Research Products

    (28 results)

All 2012 2011 2010 2009 Other

All Journal Article (15 results) (of which Peer Reviewed: 12 results) Presentation (11 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Spatio-temporal Control of Hepatic Stellate Cell-Endothelial Cell Interactions for Reconstruction of Liver Sinusoids in vitro2012

    • Author(s)
      Kasuya J, Sudo R, Mitaka T, Ikeda M, Tanishita K
    • Journal Title

      Tissue Engineer A

      Volume: 18 Pages: 1045-1056

    • DOI

      doi:10.1089/ten.tea

    • Peer Reviewed
  • [Journal Article] Growth ability and repopulation efficiency of transplanted hepatic stem, progenitor cells, and mature hepatocytes in retrorsine-treated rat livers2012

    • Author(s)
      Ichinohe N, Kon J, Sasaki K, Nakamura Y, Ooe H, Tanimizu N, Mitaka T
    • Journal Title

      Cell Transplant

      Volume: 21 Pages: 11-22

    • DOI

      doi:10.3727/096368911X580626

    • Peer Reviewed
  • [Journal Article] Proliferation of rat small hepatocytes depends on follistatin expression2012

    • Author(s)
      Ooe H, Chen Q, Kon J, Sasaki K, Miyoshi H, Ichinohe N, Tanimizu N, Mitaka T
    • Journal Title

      J Cell Physiol

      Volume: 227 Pages: 2363-2370

    • DOI

      doi:10.1002/jcp.22971

    • Peer Reviewed
  • [Journal Article] Isolation of hepatic progenitor cells from the galactosamine-treated rat liver2012

    • Author(s)
      Ichinohe N, Kon J, Mitaka T
    • Journal Title

      Methods Mol Biol

      Volume: 826 Pages: 49-58

    • DOI

      doi:10.1007/978-1-61779-468-1_5

    • Peer Reviewed
  • [Journal Article] Reconstruction of 3D stacked-up hepatocyte tissues by degradation of microporous poly(D, L-lactide-co-glycolide acids) membranes2012

    • Author(s)
      Kasuya J, Sudo R, Tamogami R, Masuda G, Mitaka T, Tanishita K
    • Journal Title

      Biomaterials

      Volume: 33(9) Pages: 2693-2700

    • URL

      http://dx.doi.org/10.1016/j.biomaterials.2011.12.039

    • Peer Reviewed
  • [Journal Article] An antibody to the lutheran glycoprotein(Lu) recognizing the LU4 blood type variant inhibits cell adhesion to laminin alpha52011

    • Author(s)
      Kikkawa Y, et al
    • Journal Title

      PLoS One

      Volume: 6(8) Pages: e23329

    • DOI

      doi:10.1371/journal.pone.0023329

    • Peer Reviewed
  • [Journal Article] Hepatic stellate cell-mediated 3D tri-culture model of hepatocytes and endothelial cells2011

    • Author(s)
      Kasuya J, Sudo R, Mitaka T, Ikeda M, Tanishita K
    • Journal Title

      Tissue Eng A

      Volume: 17 Pages: 361-370

    • DOI

      doi:10.1089/ten.tea.2010.0033

    • Peer Reviewed
  • [Journal Article] Liver stem/progenitor cells : their characteristics and regulatory mechanisms.2011

    • Author(s)
      Tanaka M, Itoh T, Tanimizu N, Miyajima A
    • Journal Title

      J Biochem

      Volume: 149(3) Pages: 231-239

    • DOI

      doi:10.1093/jb/mvr001

    • Peer Reviewed
  • [Journal Article] 障害肝と肝細胞移植2011

    • Author(s)
      中村幸雄、水口徹, 三高俊広, 平田公一
    • Journal Title

      Surgery Frontier

      Volume: 18 Pages: 288-291

  • [Journal Article] Drug Metabolism Reviews focusing on drug transporter interactions in the liver : Characterization of hepatic-organoid cultures2010

    • Author(s)
      Mitaka T, Ooe H
    • Journal Title

      Drug Metab Rev

      Volume: 42 Pages: 472-481

    • DOI

      doi:10.3109/03602530903492020

    • Peer Reviewed
  • [Journal Article] 消化器外科と再生医療-肝細胞移植研究の現状と将来展望-2010

    • Author(s)
      水口徹、三高俊広、平田公一、他
    • Journal Title

      消化器外科

      Volume: 33巻3号 Pages: 373-380

  • [Journal Article] Impaired liver regeneration with humoral and genetic disturbances in urinary trypsin inhibitor-deficient mice2009

    • Author(s)
      Nobuoka T, Mizuguchi T, Mitaka T, Hirata K
    • Journal Title

      Liver Int

      Volume: 29 Pages: 979-987

    • DOI

      DOI:10.1111/j.1478-3231.2009.01990.x

    • Peer Reviewed
  • [Journal Article] Thyroid hormone is necessary for expression of constitutive androstane receptor in rat hepatocytes2009

    • Author(s)
      Ooe H, Kon J, Oshima H, Mitaka T
    • Journal Title

      Drug Metabol Dispos

      Volume: 37 Pages: 1963-1969

    • DOI

      doi:10.1124/dmd.108.022905

    • Peer Reviewed
  • [Journal Article] Thy1-positive cells have bipotential ability to differentiate into hepatocytes and biliary epithelial cells in galactosamine-induced rat liver regeneration2009

    • Author(s)
      Kon J, Ichinohe N, Ooe H, Chen Q, Sasaki K, Mitaka T
    • Journal Title

      Am J Pathol

      Volume: 175(6) Pages: 2362-2371

    • Peer Reviewed
  • [Journal Article] 肝臓における幹細胞2009

    • Author(s)
      市戸義久、今純子、大栄秀和、三高俊広
    • Journal Title

      肝胆膵

      Volume: 59巻4号 Pages: 573-580

  • [Presentation] Hepatic Progenitor Cell Transplantation for Improving Survival after Liver Resection of Rat Non-alcoholic Steatocirrhotic Liver Model2012

    • Author(s)
      Nakamura Y, et al
    • Organizer
      7^<th> Annual Academic Surgical Congress, Quick shot oral presentation
    • Place of Presentation
      Las Vegas, NV, USA
    • Year and Date
      20120214-16
  • [Presentation] Differentiation potential of cholangiocytes2011

    • Author(s)
      Tanimizu N, et al
    • Organizer
      Liver Down Under : Liver development, diseases & regeneration
    • Place of Presentation
      Perth, Australia
    • Year and Date
      20111128-1202
  • [Presentation] Restricted differentiation of hepatic stem/progenitor cells isolated from D-galactosamine-treated rat livers2011

    • Author(s)
      Mitaka T, et al
    • Organizer
      Liver Down Under : Liver development, diseases & regeneration
    • Place of Presentation
      Perth, Australia
    • Year and Date
      20111128-1202
  • [Presentation] Role of laminin in bile duct morphogenesis. Epithelial plasticity and epithelial to mesenchymal transition2011

    • Author(s)
      Tanimizu N, et al
    • Organizer
      Keystone Symposia on Molecular and Cellular Biology
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      20110121-26
  • [Presentation] 肝前駆細胞移植治療におけるレシピエントラット肝再生機序の解析2011

    • Author(s)
      市戸義久, 他
    • Organizer
      第18回肝細胞研究会
    • Place of Presentation
      東京都
    • Year and Date
      2011-06-24
  • [Presentation] Intrahepatic distribution, preservation and transplantation of hepatocyte progenitor cells isolated from adult liver in human and rat2010

    • Author(s)
      Hirata K, et al
    • Organizer
      18^<th> United European Gastroenterology Week
    • Place of Presentation
      Barcelona, Spain
    • Year and Date
      20101023-27
  • [Presentation] ワークショップ16肝胆膵疾患と組織幹細胞/progenitor cell :病態解析と治療戦略「肝幹・前駆細胞の分化誘導因子の解析」2010

    • Author(s)
      市戸義久, 他
    • Organizer
      JDDW2010
    • Place of Presentation
      横浜市
    • Year and Date
      2010-10-14
  • [Presentation] パネルディスカッション4肝臓の再生機構を考える:今後の肝再生医療への展望:「肝幹・前駆細胞の分化・再生能力」2010

    • Author(s)
      三高俊広、他
    • Organizer
      JDDW2010
    • Place of Presentation
      横浜市
    • Year and Date
      2010-10-13
  • [Presentation] 特別講演「幹細胞と肝組織再構築」2010

    • Author(s)
      三高俊広
    • Organizer
      第22回代用臓器・再生医学研究会総会
    • Place of Presentation
      札幌市
    • Year and Date
      2010-01-23
  • [Presentation] Thy1/CD44両陽性肝前駆細胞の分化機序の解析2009

    • Author(s)
      市戸義久、今純子、大栄秀和、中村幸雄、三高俊広
    • Organizer
      第16回肝細胞研究会
    • Place of Presentation
      山形市
    • Year and Date
      2009-06-27
  • [Presentation] 特別講演「肝幹細胞と組織再構築:肝再生医療へ向けて2009

    • Author(s)
      三高俊広
    • Organizer
      第35回日本急性肝不全研究会
    • Place of Presentation
      神戸市
    • Year and Date
      2009-06-03
  • [Book] 「各種肝病態における肝オーバル細胞・小型肝細胞の同定」再生医学叢書第5巻、第5章肝細胞の機能制御・分化誘導2012

    • Author(s)
      市戸義久、大栄秀和、谷水直樹、三高俊広
    • Publisher
      朝倉書店(印刷中)
  • [Remarks]

    • URL

      http://web.sapmed.ac.jp/canpath/Tissue_Regeneration/Top_page.html

URL: 

Published: 2013-07-31  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi