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

2005 Fiscal Year Final Research Report Summary

Identification of human cord blood-derived hepatic stem cells, and establishment of cell therapy for lethal liver disease

Research Project

Project/Area Number 16590581
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionThe University of Tokyo (2005)
Tokyo Medical and Dental University (2004)

Principal Investigator

KAKINUMA Sei  The University of Tokyo, Institute of Medical Science, Research associate, 医科学研究所, 産学官連携研究員(特任助手) (30372444)

Co-Investigator(Kenkyū-buntansha) SAKAMOTO Naoya  Tokyo Medical and Dental University, Graduate school, Research associate, 大学院・医歯学総合研究科, 寄附講座教員 (10334418)
ARAKI Akihiro  Tokyo Medical and Dental University, Hospital in faculty of medicine, Research associate, 医学部附属病院, 助手 (80361690)
WATANABE Mamoru  Tokyo Medical and Dental University, Graduate school, Chief Professor, 大学院・医歯学総合研究科, 教授 (10175127)
Project Period (FY) 2004 – 2005
Keywordsumbilical cord blood / hepatocytes / stem cells / cell transplantation / liver injury / FACS / regenerative medicine / cell biology
Research Abstract

In this grant in aid for scientific research, we carried out a research project on development of cell therapy using human umbilical cord blood. In the project, we planned that identification of hepatic stem cells from cord blood through in vitro and in vivo assay, and establishment of therapeutic animal models for lethal liver disease using cord blood cell after the treatment of differentiation into functional hepatocytes. The outcome of the research was as follows.
At first, we purified the cells derived from cord blood using fluorescence-activated cell sorter. The positive and negative fractions of cell surface markers (i.e., CD45, CD34, c-met, lineage markers, and so on) were sorted, and were cultured in our original medium supplemented with FGF-1, FGF-2, HGF, SCF and LIF. In this culture condition, total cord blood cells were able to produce albumin and metabolite ammonia. The in vitro assay revealed that the purified CD45-positive cells and lineage markers-negative cells derived f … More rom cord blood can express albumin mRNA. Further examination showed that purified CD34-positive cells were able to express albumin mRNA in our original culture condition.
Next, we performed a transplantation assay using purified cord blood cells. Cord blood cells were transplanted into liver-injured recipient mice, and their liver and the sera were analyzed. After the cell transplantation, the liver of recipient mice transplanted with CD34-positive cells contained human albumin-producing cells, indicating that cord blood CD34-positive cells engrafted in the liver and gave rise to hepatocytes. Furthermore, in the case of chronically liver-injured recipient mice, transplanted total cord blood cells were able to express marker-genes of functionally mature hepatocytes. These results showed that cord blood cells contain the hepatic progenitor cells, which can give rise to functionally mature hepatocytes.
In conclusion, our data implied that human umbilical cord blood could be a source of hepatic progenitor cells for liver disease. The outcome of the research project will be a basis of liver regenerative medicine, and we think the purpose of this grant in aid for scientific research was accomplished. Less

  • Research Products

    (12 results)

All 2006 2005 2004

All Journal Article (11 results) Book (1 results)

  • [Journal Article] ヒト臍帯血細胞の肝細胞への誘導と細胞移植2006

    • Author(s)
      柿沼 晴
    • Journal Title

      炎症・再生 26(1)

      Pages: 44-48

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] がん幹細胞 : 新規治療開発への展望2006

    • Author(s)
      柿沼 晴, 他
    • Journal Title

      医学のあゆみ (掲載予定)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Functional hepatocyte-like cells derived from human umbilical cord blood2006

    • Author(s)
      Kakinuma S
    • Journal Title

      Inflammation and Regeneration (Japanese) 26(1)

      Pages: 44-48

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Cancer Stem Cells ; A potential basis for developing a novel therapeutic approach2006

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

      Igaku-no-Ayumi (Japanese) 217(suppl 1)

      Pages: 125-128

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Functional hepatocytes derived from umbilical cord blood2006

    • Author(s)
      Kakinuma S, (In : Arakawa Y, eds.)
    • Journal Title

      Progress in gastroenterology 2005-Monograph-Frontier of gastroenterology (Tokyo : Medical Review Press)

      Pages: 344-349

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Hepatocyte differentiation from embryonic stem cells and umbilical cord blood cells.2005

    • Author(s)
      Teramoto K, Kakinuma S, et al.
    • Journal Title

      Journal of Hepato-Biliary-Pancreatic Surgery 12(3)

      Pages: 196-202

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Increase of bone marrow-derived secretory lineage epithelial cells during regeneration in the human intestine.2005

    • Author(s)
      Matsumoto T, Watanabe M, et al.
    • Journal Title

      Gastroenterology 128(7)

      Pages: 1851-1867

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Suppression of hepatitis C virus replication by cyclosporin A is mediated by blockade of cyclophilins.2005

    • Author(s)
      Nakagawa M, Kakinuma S, et al.
    • Journal Title

      Gastroenterology 129(3)

      Pages: 1031-1041

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Suppression of hepatitis C virus replication by cyclosporin A is mediated by blockade of cyclophilins.2005

    • Author(s)
      Nakagawa M, Sakamoto N, Kakinuma S, Watanabe M et al.
    • Journal Title

      Gastroenterology 129(3)

      Pages: 1031-1041

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Transplantation of human umbilical cord blood cells to injured liver2004

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

      Gastroenterology 126(suppl2)

      Pages: A753

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Transplantation of human umbilical cord blood cells to injured liver.2004

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

      Gastroenterology 126 suppl 2

      Pages: A753

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] 臍帯血由来細胞の機能的肝細胞への誘導(消化器病学の進歩2005-モノグラフ 消化器病学のニューフロンティア編)2005

    • Author(s)
      柿沼 晴(荒川泰之編・分著)
    • Total Pages
      5(1007)
    • Publisher
      メディカルレビュー社
    • Description
      「研究成果報告書概要(和文)」より

URL: 

Published: 2007-12-13  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi