2003 Fiscal Year Final Research Report Summary
Basic research of the treatment for hepatic failure by hepatocyte transplantation
| Project/Area Number |
13557107
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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 | Sapporo Medical University |
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Principal Investigator |
HIRATA Koichi Sapporo Medical University, 1st Department of Surgery, Professor, 医学部, 教授 (50136959)
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| Co-Investigator(Kenkyū-buntansha) |
MITAKA Toshihiro Sapporo Medical University, Department of Pathophysiology Cancer Research Institute, Assistant Professor, 医学部, 教授
KATSURAMAKI Tadashi Sapporo Medical University, 1st Department of Surgery, Assistant Professor, 医学部, 助教授 (50253993)
古畑 智久 札幌医科大学, 医学部, 講師 (80359992)
MIZUGUCHI Toru Sapporo Medical University, 1st Department of Surgery, Assistant Professor, 医学部, 講師 (30347174)
本間 敏男 札幌医科大学, 医学部, 助手
KIMURA Yasutoshi Sapporo Medical University, 1st Department of Surgery, Instructor, 医学部, 助手 (80311893)
TSURUMA Tetsuhiro Sapporo Medical University, 1st Department of Surgery, Assistant Professor (80381268)
NOBUOKA Takayuki Sapporo Medical University, 1st Department of Surgery, Instructor (70359991)
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| Project Period (FY) |
2001 – 2003
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| Keywords | hepatic failure / hepatosyte / stem cell / small hepatocyte / transplantation / cholestasis / bile canalicutus / sepsis |
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| Research Abstract |
[Background] It is envisaged that hepatocyte transplantation and extracorporeal liver support systems may be a future alternative therapy to orthotopic liver transplantation. Small hepatocytes known as liver hepatocyte stem cells would be considered to be more adequate in hepatoyte transplantation. In addition, if a kind of specific function by a gene transfection to small hepatocytes was inducted, some benefits would provide for the patients with hepatic failure.
[Object] At first, small hepatocytes were determined as the objective cell source in hepatocyte transplantation. Whether alternative changes of contructed hepatocytes from recipient hepatocytes to small hepatocytes might occur or not has been studied. Therefore, PDX 1 gene, an insulin-producing gene, was tranfected to small hepatocytes by adenovial infection and those stem cells were analysed about the functional maintenance in vitro and in vivo. And the possibility of hepatosyte transplantation by those cells has been tried.
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Experimental Classification] This research is composed of three kinds of experiments as shown as followings.
(1) Establishment of the transfection method of insulin-production gene. The transfection of PDX-1 gene, as an insulin-producing gene to adult hepatocytes and to small hepatocytes had been studied by the infection of adenoviral vectors. The expression of transfere genes, the production of pancreatic endocrine hormones and the characteristics of the hepatocytes were immurohis topathologically made sure in the transfected cells.
(2) Expression and production of insulin in the transfected cells. Immunohistologic determination of the transfected cells, analysis of m-RNA specific to the proteins, maintenance of function in the transfected cells were studied.
(3) Hepatocyte transplantation in vivo. Small hepatocyte or adult hepatocytes with or without transfection of the gene were transplanted into liver via the injection into spleen.
[Results] All of above research plans have been performed during 2001 to 2004, as shown in followings.
(1) Expression of several transfere factors were determined in the infected cells after the transfection of PDX-1. The quantitations of insulin, glucagon, somatostatin and pancreatic polypeptide in the cultured solution were succeeded. But it was very difficult to get the stable transfection and to repeat this experiment successfully.
(2) The transfection rates were extremely low but was observed higher in the adult hepatocytes than in small hepatocytes. The limitation of the maintenance of the function gained by transfection was strongly impressed on this research.
(3) Highly succeeded repopulation in the recipient liver was observed in the experiment with non gene transfected small hepatocytes and the proliferation of small hepatocyte in injected was also confident.
[Conclusion] This pilot research suggest that small hepatocytes transplantations would invite an entrance of the actuarial utilization of clinics. Less
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[Journal Article] Efficacy of SPIO-MR imaging in the diagnosis of liver metastases from colorectal carcinomas.2003
Author(s)
Furuhata T, Okita K, Tsuruma T, I data F, Kimura Y, Katsuramaki T, Mukaiya M, I lirokawa N, Ichimura T, Yama N, Koito K, Sasaki K, Hirata K
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Journal Title
Digest Surg 20
Pages: 321-325
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Efficacy of SPIO-MR imaging in the diagnosis of liver metastases from colorectal carcinomas.2003
Author(s)
Furuhata T, Okita K, Tsuruma T, Hata F, Kimura Y, Katsuramaki T, Mukaiya M, Hirokawa N, Ichimura T, Yama N, Koito K, Sasaki K, Hirata K
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Journal Title
Digest Surg 20
Pages: 321-325
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Long-Term Culture of Primary Human Hepatocytes with Preservation of Proliferative Capacity and Differentiated Functions.2002
Author(s)
Katsura N, Ikai I, Mitaka T, Shiotani T, Matsushita T, Yamanokuchi S, Sugimoto S, Kanazawa A, Terajima H, Mochizuki Y, Yamaoka Y
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Journal Title
J Surg Res 106(1)
Pages: 115-123
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Changes in the serum levels of apolipoprotein A-1 as an indicator of protein metabolism after hepatectomy.2002
Author(s)
Katsuramaki T, Hirata K, Kimura Y, Nagayama M, Meguro M, Kimura H, Honma T, Furuhata T, Ura H, Hata F, Mukaiya M
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Journal Title
Wound Rep Reg 10
Pages: 77-82
Description
「研究成果報告書概要(和文)」より
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