1999 Fiscal Year Final Research Report Summary
Development of therapy for regulation of liver cirrhosis by antisense gene and transplantation of proliferative hepatocyte
| Project/Area Number |
09557100
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Digestive surgery
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| Research Institution | TOHOKU UNIVERSITY |
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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)
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| 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)
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| Project Period (FY) |
1997 – 1999
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| Keywords | liver cirrhosis / liver regeneration / gene therapy / antisense / cell fusion |
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| 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.
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