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Development of therapy for regulation of liver cirrhosis by antisense gene and transplantation of proliferative hepatocyte

Research Project

Project/Area Number 09557100
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Digestive surgery
Research InstitutionTOHOKU UNIVERSITY

Principal Investigator

OHKOHCHI Nobuhiro  Graduate Sch. of Medicine, Tohoku Univ., Associate Prof., 大学院・医学系研究科, 助教授 (40213673)

Co-Investigator(Kenkyū-buntansha) DOI Hideyuki  Tohoku University Hospital, Lecturer, 医学部・附属病院, 講師 (90188839)
TAGUCHI Yoshio  International Student Center, Tohoku Univ., Professor, 留学生センター, 教授 (70004885)
SATOMI Susumu  Graduate Sch. of Medicine, Tohoku Univ., Professor, 大学院・医学系研究科, 教授 (00154120)
SEKIGUCHI Satoshi  Tohoku University Hospital, Research Associate, 医学部・附属病院, 助手 (20312580)
ORII Takashi  Tohoku University Hospital, Research Associate, 医学部・附属病院, 助手 (20282048)
桜田 正寿  東北大学, 医学部・附属病院, 助手 (40292320)
西平 哲郎  東北大学, 医学部, 助教授 (50101142)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥9,400,000 (Direct Cost: ¥9,400,000)
Fiscal Year 1999: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1997: ¥4,200,000 (Direct Cost: ¥4,200,000)
Keywordsliver cirrhosis / liver regeneration / gene therapy / antisense / cell fusion / 肝切除 / 増殖性肝細胞 / 移植 / ハイブリッド肝細胞 / アンチ・センス / コラゲナーゼインヒビター / 遺伝子導入
Research Abstract

Experiment 1 : For establishment of an animal model with liver cirrhosis, CCl4 and dimethyl nitrosoamine (DMNA) were administered to mouse and rat. Liver of animals with administration of CCl4 were cirrhotic but parenchymal hepatocyte was injured so severely. On the other hand, liver of rat with administration of DMNA was sever cirrhotic and hepatocyte seemed to be almost normal. Therefore, we conclude that rat with administration of DMNA was suitable for experiment of cirrhosis. Experiment 2 : In model with liver cirrhosis efficucies of HGF and antagonist of TGFb administration were examined after liver resection. HGF had an effect on progress of regeneration but antagonist of TGFb had no remarkable effect on regeneration and it counteracted the effect of HGF. Experiment 3 : For making hybridoma which has function of hepatocyte and proliferates, we tried to make cell fusion equipment using laser. Using this device, we could make hybridoma from mouse myeloma cells and lymphocytes. We made clone from this hybridoma and examined characters of both original cells. In addition we made hybridoma with myeloma cells and hepatocytes and are investigating the character of this hybridoma now. Experiment 4 : For treatment of cell function by gene transduction, we carried out the preliminary study that antisense for mRNA of TNF was encapsuled with HVJ liposome and was transfected to Kupffer cells. With antisense therapy, production of TNF decreased to 40%. Now using Ito cells, effect of antisense therapy is investigating. Gene therapy using antisense of mRNA of collagenase inhibitor is still not done yet.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (2 results)

All Other

All Publications (2 results)

  • [Publications] Ohkohchi N.et al.(5): "New teqnique for producing hybridoma using laser radiation"Laser in Surgery and Medicine. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ohkohchi, N. et al (5): "New teqnique for producing hybridoma using laser radiation"Laser in Surgery and Medicine. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary

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Published: 1997-04-01   Modified: 2016-04-21  

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