| Project/Area Number |
12470265
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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 | 一般 |
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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 Univ., School of Medicine, Professor, 医学部, 教授 (50136959)
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| Co-Investigator(Kenkyū-buntansha) |
FURUHATA Tomohisa Sapporo Medical Univ., School of Medicine, Instructor, 医学部, 講師 (80359992)
KATSURAMAKI Tadashi Sapporo Medical Univ., School of Medicine, Assce.Professor, 医学部, 助教授 (50253993)
MITAKA Toshihiro Sapporo Medical Univ., School of Medicine, Professor, 医学部, 教授 (50231618)
MIZUGUCHI Toru Sapporo Medical Univ., School of Medicine, Instructor, 医学部, 助手 (30347174)
HONMA Toshio Sapporo Medical Univ., School of Medicine, Instructor, 医学部, 助手 (30315494)
望月 洋一 札幌医科大学, 附属がん研究所, 教授 (40045381)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥13,600,000 (Direct Cost: ¥13,600,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2000: ¥9,200,000 (Direct Cost: ¥9,200,000)
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| Keywords | Bile stasis / Hepatic failure / Artificial liver / Cell transplantation / Small hepatocyte / Bile canaliculus / Bilirubin transport / Infection / ヒト / 細胞分化 / 分化能 / 冷凍保存 / 肝細胞形質 / 正常肝細胞 / 毛細胆管 / 肝細胞 / 周術期 / サイトカイン / 感染症 / ヒトAGP / AGPR |
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| Research Abstract |
This research program was composed of three components, namely the first is"the establishment extracorporeal hepatic tissue structure", the second is"the study of bile stasis under in vitro condition" and the third is "the treatment of hepatic failure by cell transplantation". The first one is most important research extending to the regenerative medicine and to the tartificial liver. The culture of small hepatocyte invited the organoid structure resembling with liver, tissue. Moreover, small hepatocytes maintain growth ability and hepatic differentiated functions even after long-term cryopreservation. This result means that the establishment of isolation method for mouse and human hepatocytes will be important, and the application of the method shown in this study may be useful for the establishment of a hepatocyte bank and development of an artificial liver. The second research was performed by the number of bile canalicular contractions in the couplets treated with cytokines. The ra
… More
pid movement of a droplet from bilecanaliculus was observed at the intercellular space of the hepatocyte couplet treated with TNF-α. And TNF-αand IL-6 reduce bile canaliculus contractions. Moreover, the similar result was observed in the movement of bile canaliculus formed in hepatic organoid structure reconstructed by rat small hepatocytes and nonparenchymal cells.
The utilization of those hepatic cells referred to cell transplantation into a liver. The successful proliferation of the injected hepatocyte observed in some cases, but reproducible results in experiments have not been established. Further efforts would be required for the establishment of hepatocytic stem cell transplantation in liver tissue.
In summary, we demonstrated that, the culture of small hepatocyte provides a hepatoid structure, improves hepatocyte differentiation and maintains a tissue-specific plans typical characteristics. This might have a significant therapeutic impact on the care of the patients with liver failure. Less
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