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Experimental research for treatment of liver failure with hepatic tissue stem cell (SP cell)

Research Project

Project/Area Number 14207026
Research Category

Grant-in-Aid for Scientific Research (A)

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

Principal Investigator

HORIE Yoshinori (2004)  Keio University, Department of Medicine, Assistant Professor, 医学部, 講師 (70229227)

石井 裕正 (2002-2003)  慶應義塾大学, 医学部, 教授 (20051500)

Co-Investigator(Kenkyū-buntansha) KATO Shinzo  Keio University, Department of Medicine, Assistant Professor, 医学部, 講師 (30177448)
SAITO Hidetsugu  Keio University, Department of Medicine, Assistant Professor, 医学部, 講師 (80186949)
TOMITA Kengo  Keio University, Department of Medicine, Research Assistant, 医学部, 助手 (50317129)
INOKUCHI Sayaka  Keio University, Department of Medicine, Research Assistant, 医学部, 助手 (00383711)
OKANO Hideyuki  Keio University, Department of Medicine, Professor, 医学部, 教授 (60160694)
堀江 義則  慶應義塾大学, 医学部, 専任講師 (70229227)
東 俊文  慶應義塾大学, 医学部, 専任講師 (00222612)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥42,770,000 (Direct Cost: ¥32,900,000、Indirect Cost: ¥9,870,000)
Fiscal Year 2004: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2003: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2002: ¥31,720,000 (Direct Cost: ¥24,400,000、Indirect Cost: ¥7,320,000)
Keywordsside population cell / stem cell autotransplantation / collagen gel sandwich configuration / hepatic differentiation induction method / 肝細胞分化 / 脾臓 / 自家細胞移植 / 肝再生 / 細胞融合 / 移植医療 / 肝硬変 / 肝不全 / 初代培養肝細胞 / コラーゲンゲル / 幹細胞
Research Abstract

1. Hepatic differentiation induction method in vitro
In an effort to reconstruct the hepatocyte function and cellular polarity normally found in the liver, adult rat hepatocytes were sandwiched between two layers of hydrated collagen matrix. Functionally, sandwiched hepatocytes maintained the secretion of albumin, the expression of liver specific proteins and the distribution of actin filaments, whereas the cells cultured on single layer of collagen gel decreased the albumin secretion, the liver specific proteins and showed abnormal formation of actin stress fibers and cell spreading. Overlaying a second layer of collagen gels on the hepatocytes that had been cultured on a single gel reversed the cell spreading, reduced actin stress fibers and recovered the liver specific protein expressions.
Bone marrow cells could differentiate into hepatocytes when they co-cultured with primary cultured hepatocytes in collagen gel sandwich indicating that hepatocytes cultured in collagen gel sandwich was functionally good enough to induce differentiation of bone marrow cell into hepatocytes.
2. SP cells
We could successfully induce SP cells derived from liver and bone marrow transdifferentiation into hepatocytes in vitro and in vivo. Splenic SP cells have a remarkable capacity for hepatic differentiation, as they were co-cultured with primary cultured hepatocytes in collagen gel. It is our great surprise that the prevalence of SP cells in spleen is 5 to 10 times higher than in bone marrow. Our results indicated that splenic-SP cells might have the potential to transdifferentiate into hepatocytes. Since the prevalence of SP cells in spleen is much higher than in bone marrow, total amount of SP cells could be much larger. Thus the spleen could have the highest prevalence of SP cells and spleen could provide an alternative source of stem cell for stem cell transplantation into liver.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report

Research Products

(17 results)

All 2004 2003 Other

All Journal Article (6 results) Publications (11 results)

  • [Journal Article] コラーゲンゲルサンドイッチ法が初代培養肝細胞の機能・分化機構に及ぼす影響2004

    • Author(s)
      井口清香
    • Journal Title

      慶應医学 81

      Pages: 49-60

    • NAID

      10017043341

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 体性幹細胞の分化におけるサイトケラチン発現の意義2004

    • Author(s)
      西村健, 他
    • Journal Title

      肝サイトスケレトン研究会誌 14

      Pages: 35-38

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of collagen gel sandwich on functions and differentiation mechanisms in primary cultured hepatocytes2004

    • Author(s)
      Sayaka Inokuchi
    • Journal Title

      Journal of the Keio Medical Society 81

      Pages: 49-60

    • NAID

      10017043341

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Role of cytokeratin expression at tissue stem cell differentiation2004

    • Author(s)
      Takeshi Nishimura, et al.
    • Journal Title

      Journal of the Hepatic Cytoskeleton Society 14

      Pages: 35-38

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 初代培養肝細胞における肝細胞機能分化と細胞骨格2003

    • Author(s)
      井口清香, 他
    • Journal Title

      肝サイトスケレトン研究会誌 13

      Pages: 17-20

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hepatic differentiated function and cell cytoskeleton of primary culture hepatocyte2003

    • Author(s)
      Sayaka Inokuchi, et al.
    • Journal Title

      Journal of the Hepatic Cytoskeleton Society 13

      Pages: 17-20

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Horie Y, Yamagishi Y, Kato S, Kajihara M, Kimura H, Ishii H.: "Low-dose ethanol attenuates gut ischemia/reperfusion-induced liver injury in rats via nitric oxide production."J Gastroenterol Hepatol.. 18(2). 211-217 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ishii H, Horie Y, Tomita K, Yamagishi Y.: "Alcoholic liver diseases in Japan and modification by hepatitis virus"Nihon Arukoru Yakubutsu Igakkai Zasshi.. 38(5). 403-414 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Horie Y, Yamagishi Y, Kajihara M, Kato S, Ishii H.: "National survey of hepatocellular carcinoma in heavy drinkers in Japan."Alcohol Olin Exp Res.. 27(8 Suppl). 32S-36S (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tomita K, Azuma T, Kitamura N, Nishida J, Tamiya G, Oka A, Inokuchi S, Nishimura T, Suematsu M, Ishii H.: "Pioglitazone prevents alcohol-induced fatty liver in rats through up-regulation of c-Met."Gastroenterology. 126(3). 873-885 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tomita K, Azuma T, Inokuchi S, Kitamura N, Nishimura T, Kato S, Ishii H.: "Regulation of mouse retinol dehydrogenases and retinal dehydrogenases in hepatocyte differentiation."Nihon Arukoru Yakubutsu Igakkai Zasshi.. 38(1). 46-57 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ishii H.: "Physiopathology and treatment of alcoholic liver dysfunctions"Nippon Naika Gakkai Zasshi.. 91. 243-248 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Horie Y, Yamagishi Y, Kato S, Kajihara M, Kimura H, Ishii: "Low-dose ethanol attenuates gut ischemia/repertusion-induced liver injury in rats via nitric oxide production"J Gastroenterol Hepatol.. 18(2). 211-217 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamagishi Y, Saito H, Shimadu M, Hoshino K, Kobayashi H, Nakamoto N, Horie Y, Kato S, Morikawa Y, Kitajima M., Ishii H.: "Intensive therapy for fulminant hepatic failure: importance of co-operation between physicians of internal medicine and transplantation surgery"Nippon Shokakibyo Gakkai Zasshi.. 99(10). 1205-1207 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tamai H, Horie Y, Kato S, Yokoyama H, Ishii H.: "Long-term ethanol feeding enhances susceptibility of the liver to orally administered lipopolysaccharides in rats"Alcohol Clin Exp Res.. 26(8 Suppl). 75S-80S (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Horie Y, Yamagishi Y, Kato S, Kajihara M, Tamai H, Granger DN: "Role of ICAM-1 in chronic ethanol consumption-enhanced liver injury after gut ischemia-reperfusion in rats"Am J Physiol Gastrointest Liver Physiol.. 283(3). G537-G543 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Adachi M, Ishii H.: "Role of mitochondria in alcoholic liver injury"Free Radic Biol Med.. 32(6). 487-491 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-03-31   Modified: 2016-04-21  

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