2001 Fiscal Year Annual Research Report

肝細胞移植による肝不全治療を目的とした基礎的研究

Research Project

Project/Area Number	13557107
Research Institution	Sapporo Medical University
Principal Investigator	平田公一札幌医科大学, 医学部, 教授 (50136959)
Co-Investigator(Kenkyū-buntansha)	古畑智久札幌医科大学, 医学部, 助手桂巻正札幌医科大学, 医学部, 助教授 (50253993) 三高俊広札幌医科大学, 附属がん研究所, 助教授 (50231618) 本間敏男札幌医科大学, 医学部, 助手 (30315494)
Keywords	小型肝細胞 / インスリン / 遺伝子導入 / 細胞移植 / ミニ肝組織
Research Abstract	平成13年度中にラット肝臓より小型肝細胞を採取し、それを増殖させてミニ肝組織を形成させることについては安定した技術として繰り返し可能であった。このほか最終的な細胞移植応用段階で必要となるであろう肝非実習細胞(Kupffer細胞、血管内皮細胞、胆管上皮細胞など)や成熟肝実質細胞の分離採取も安定した技術として完成した。次にこれら細胞の移植において臨床応用のために必要となる凍結保存、解凍後培養を試みたところ2週間、1ヵ月、3ヵ月の保存のいずれにおいても可能であった。そこでこれを同系動物種の門脈内注入による肝内への移植を行い一定期間後の移植細胞の同定を試みたが、明瞭なfoci形成などの所見を得ることができていない状況にある。生着していない危険率は高いと想定しているが、同定および移植後の肝内での増殖の確立を早急に行うことが要求されている。現在レシピエントとドナー間の関係について異性間での相互移植、すなわち分離細胞と被移植肝に性差を設定して容易な同定について検討中である。一方、遺伝子導入についてはリポフェクチン法を用いてインスリン産生に関わる遺伝子を小肝細胞に遺伝子導入を試みている。当初、導入直後、小肝細胞に増殖が止まるなどのトラブルを生じていたが最近では変性死することはなくなりつつあるが、分泌蛋白としてインスリンを同定しえていないのが現状である。さらなる努力を続けたい。

Research Products

(19 results)

All Other

All Publications (19 results)

[Publications] Nishimori H, Yasoshima T, Hata F, Denno R, Yanai Y, et al.: "A Novel Nude Mouse Model of Liver Metastasis and Peritoneal Dissemination from the Same Human Pancreatic Cancer Line"Pancreas. (In press). (2002)
[Publications] M.Meguro, T katsuramaki, M Nagayama, H Kimura et al.: "A novel inhibitor of inducible nitric oxide synthase (ONO-1714) prevents critical warm ischemia-reperfusion injury in the pig liver"Transplantation Proceeding. (In press). (2002)
[Publications] T.Katsuramaki, K Hirata, T Furuhata et al.: "Preoperative Estimation of Risk in Hepatectomy Using Technetium-99m-Galactosyl Human Serum Albumin Receptor Amount by Nonlinear 3-Compartment Model (01641)"Hepato-Gastroenterology. (In press). (2002)
[Publications] T.Katsuramaki, K Hirata, Y Kimura et al.: "Changes in the serum levels of apolipoprotein A-1 as an indicator of protein metabolism after hepatectomy"Wound repair and Regenerution. (In press). (2002)
[Publications] Katsura N, Ikai I, Mitaka T, Shiotani T, Matsushita T, et al.: "Long-term culture of primary human hepatocytes with preservation of proliferative capacity and differentiated functions"J Surg Res.. (In press). (2002)
[Publications] Mizuguchi T, Palm K, Hui T, Aoki T, Mochizuki Y, Mitaka T, et al.: "Effects of bone marrow stromal cells on the structural and functional polarity of primary rat heptocytes"In Vitro Cell Dev Biol. (In press). (2002)
[Publications] Takagi C, Ueki K, Ikeuchi H, Kuroiwa T, Kaneko Y, et al.: "Increased Expression of Cell Adhesion kinase β in Human and Rat Crescentic Glomerulonephritis"Am J Kid Dis. 39(1). 174-182 (2002)
[Publications] K.Hirata: "Sepsis and cholestasis : basic findings in the sinusoid and bile canaliculus"J Hepatobiliary Pancreat Surg. 8. 20-26 (2001)
[Publications] Mitaka T, Sato F, Ikeda S, Sugimoto S, Higaki N, et al.: "Expression of carbamoylphosphate synthetase I and glutamine synthetase in hepatic organoids reconstructed by rat small hepatocytes and hepatic nonparenchymal cells"Cell Tissue Res.. 306. 467-471 (2001)
[Publications] Mizuguchi T, Hui T, Palm K, Sugiyama N, Mitaka T, et al.: "Enhanced proliferation and differentiation of rat hepatocytes cultured with bone marrow stromal cells"J. Cell. Physiol. 189(1). 106-119 (2001)
[Publications] Yanai Y, Furuhata T, Kimura Y, Yamaguchi K, Yasoshima T, et al.: "Vascular endothelial growth factor C promotes human gastric carcinoma lymph node metastasis in mice"J. Exp. Clin. Cancer Res.. 20(3). 419-428 (2001)
[Publications] Nomura, H., Nishimori H., Yasoshima, T., Hata, F et al.: "A new experimental mouse model of peritoneal dissemination of human gastric cancer cells : analysis of the mechanism of peritoneal dissemination using cDNA macroarrays"Jpn. J. Cancer Res.. 92. 748-754 (2001)
[Publications] R.Fukui, F.Hata, T.Yasoshima, T.Honma, F.Nakajima, et al.: "Adenosquamous carcinoma of the colorectum : Report of two cases"J. Exp. Clin. Cancer Res.. 20. 293-296 (2001)
[Publications] Nishimori, H.Yasoshima, Y.Denno, R.Shishido et al.: "Kawaguchi, S. Kamiguchi, K. Isomura, H. Sato, N. and Hirata, K. A New Peritoneal Dissemination Model Established from the Human Pancreatic Cancer Cell Line"Pancreas. 22. 348-356 (2001)
[Publications] 桂巻正, 木村康利, 目黒誠, 永山稔, 木村仁, 磯部将人, 他: "肝切除術における肝機能指標としての総分枝鎖アミノ酸/チロシンモル比(BTR)の変動…その有用性と問題点…"外科と代謝・栄養. 35(2). 25-32 (2001)
[Publications] N Higaki, T Mitaka, F Sato, K Hirata, Y Mochizuki: "Maintenance of connexin 32 and 26 Expression in primary cultured rat hepatocyteds treated with 3-acetylpyridine"Journal of Gastroenterology and Hepatology. 16. 806-815 (2001)
[Publications] Mizuguchi T, Kamohara Y, Hui T, Neuman T, Mitaka T, et al.: "Regulation of c-met expression in rats with acute hepatic failure"J. Surg. Res.. 99(2). 385-396 (2001)
[Publications] Higaki N, Mitaka T, Sato F, Hirata K, Mochizuki Y.: "Maintenance of connexin 32 and 26 expression in primary cultured rat hepatocytes treated with 3-acetylpyridine"J Gastroenterol Hepatol. 16(7). 806-815 (2001)
[Publications] 平田公一, 桂巻正: "クリティカルケア SIRS・ショック・MODS"(株)医学書院. 277 (2001)

2001 Fiscal Year Annual Research Report

肝細胞移植による肝不全治療を目的とした基礎的研究

Principal Investigator

平田 公一 札幌医科大学, 医学部, 教授 (50136959)

Research Products

[Publications] Nishimori H, Yasoshima T, Hata F, Denno R, Yanai Y, et al.: "A Novel Nude Mouse Model of Liver Metastasis and Peritoneal Dissemination from the Same Human Pancreatic Cancer Line"Pancreas. (In press). (2002)

[Publications] M.Meguro, T katsuramaki, M Nagayama, H Kimura et al.: "A novel inhibitor of inducible nitric oxide synthase (ONO-1714) prevents critical warm ischemia-reperfusion injury in the pig liver"Transplantation Proceeding. (In press). (2002)

[Publications] T.Katsuramaki, K Hirata, T Furuhata et al.: "Preoperative Estimation of Risk in Hepatectomy Using Technetium-99m-Galactosyl Human Serum Albumin Receptor Amount by Nonlinear 3-Compartment Model (01641)"Hepato-Gastroenterology. (In press). (2002)

[Publications] T.Katsuramaki, K Hirata, Y Kimura et al.: "Changes in the serum levels of apolipoprotein A-1 as an indicator of protein metabolism after hepatectomy"Wound repair and Regenerution. (In press). (2002)

[Publications] Katsura N, Ikai I, Mitaka T, Shiotani T, Matsushita T, et al.: "Long-term culture of primary human hepatocytes with preservation of proliferative capacity and differentiated functions"J Surg Res.. (In press). (2002)

[Publications] Mizuguchi T, Palm K, Hui T, Aoki T, Mochizuki Y, Mitaka T, et al.: "Effects of bone marrow stromal cells on the structural and functional polarity of primary rat heptocytes"In Vitro Cell Dev Biol. (In press). (2002)

[Publications] Takagi C, Ueki K, Ikeuchi H, Kuroiwa T, Kaneko Y, et al.: "Increased Expression of Cell Adhesion kinase β in Human and Rat Crescentic Glomerulonephritis"Am J Kid Dis. 39(1). 174-182 (2002)

[Publications] K.Hirata: "Sepsis and cholestasis : basic findings in the sinusoid and bile canaliculus"J Hepatobiliary Pancreat Surg. 8. 20-26 (2001)

[Publications] Mitaka T, Sato F, Ikeda S, Sugimoto S, Higaki N, et al.: "Expression of carbamoylphosphate synthetase I and glutamine synthetase in hepatic organoids reconstructed by rat small hepatocytes and hepatic nonparenchymal cells"Cell Tissue Res.. 306. 467-471 (2001)

[Publications] Mizuguchi T, Hui T, Palm K, Sugiyama N, Mitaka T, et al.: "Enhanced proliferation and differentiation of rat hepatocytes cultured with bone marrow stromal cells"J. Cell. Physiol. 189(1). 106-119 (2001)

[Publications] Yanai Y, Furuhata T, Kimura Y, Yamaguchi K, Yasoshima T, et al.: "Vascular endothelial growth factor C promotes human gastric carcinoma lymph node metastasis in mice"J. Exp. Clin. Cancer Res.. 20(3). 419-428 (2001)

[Publications] Nomura, H., Nishimori H., Yasoshima, T., Hata, F et al.: "A new experimental mouse model of peritoneal dissemination of human gastric cancer cells : analysis of the mechanism of peritoneal dissemination using cDNA macroarrays"Jpn. J. Cancer Res.. 92. 748-754 (2001)

[Publications] R.Fukui, F.Hata, T.Yasoshima, T.Honma, F.Nakajima, et al.: "Adenosquamous carcinoma of the colorectum : Report of two cases"J. Exp. Clin. Cancer Res.. 20. 293-296 (2001)

[Publications] Nishimori, H.Yasoshima, Y.Denno, R.Shishido et al.: "Kawaguchi, S. Kamiguchi, K. Isomura, H. Sato, N. and Hirata, K. A New Peritoneal Dissemination Model Established from the Human Pancreatic Cancer Cell Line"Pancreas. 22. 348-356 (2001)

[Publications] 桂巻正, 木村康利, 目黒誠, 永山稔, 木村仁, 磯部将人, 他: "肝切除術における肝機能指標としての総分枝鎖アミノ酸/チロシンモル比(BTR)の変動…その有用性と問題点…"外科と代謝・栄養. 35(2). 25-32 (2001)

[Publications] N Higaki, T Mitaka, F Sato, K Hirata, Y Mochizuki: "Maintenance of connexin 32 and 26 Expression in primary cultured rat hepatocyteds treated with 3-acetylpyridine"Journal of Gastroenterology and Hepatology. 16. 806-815 (2001)

[Publications] Mizuguchi T, Kamohara Y, Hui T, Neuman T, Mitaka T, et al.: "Regulation of c-met expression in rats with acute hepatic failure"J. Surg. Res.. 99(2). 385-396 (2001)

[Publications] Higaki N, Mitaka T, Sato F, Hirata K, Mochizuki Y.: "Maintenance of connexin 32 and 26 expression in primary cultured rat hepatocytes treated with 3-acetylpyridine"J Gastroenterol Hepatol. 16(7). 806-815 (2001)

[Publications] 平田公一, 桂巻 正: "クリティカルケア SIRS・ショック・MODS"(株)医学書院. 277 (2001)

平田公一札幌医科大学, 医学部, 教授 (50136959)

[Publications] 平田公一, 桂巻正: "クリティカルケア SIRS・ショック・MODS"(株)医学書院. 277 (2001)