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Identification of specific surface proteins in small hepatocytes and reconstruction of hepatic organoids ex vivo.

Research Project

Project/Area Number 14370393
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionSapporo Medical University School of Medicine

Principal Investigator

MITAKA Toshihiro  Cancer Research Institute, Professor, 附属がん研究所, 教授 (50231618)

Co-Investigator(Kenkyū-buntansha) TAKEDA Hiroshi  Cancer Research Institute, Instructor, 附属がん研究所, 助手 (00333310)
KIKKAWA Yamato  Cancer Research Institute, Instructor, 附属がん研究所, 助手 (20274227)
HIRATA Koichi  Medical School, Professor, 医学部, 教授 (50136959)
KATSUMMALA Tadashi  Medical School, Associate Professor, 医学部, 助教授 (50253993)
MIZUGUCHI Toru  Medical School, Assistant Professor, 医学部, 講師 (30347174)
本間 敏男  札幌医科大学, 医学部, 助手 (30315494)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2004: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2003: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2002: ¥6,000,000 (Direct Cost: ¥6,000,000)
Keywordssmall hepatocytes / progenitor cells / ex vivo hepatic organoid / cell transplantation / three-dimensional culture / specific membrane protein / hepatocyte replacement / scaffold / 小型肝細胞特異的遺伝子 / 低重力環境 / 凍結保存 / ヒト肝細胞 / 肝組織構築 / 人工肝臓 / 薬物代謝酵素 / 成熟化 / チトクロームP450 / 移植
Research Abstract

We found three genes, CD44, BRI3, and D6.1A, with much higher expression in small hepatocytes (SHs)than in mature hepatocytes (MHs)and possessing transmembrane domain. Using specific antibody to CD44, BRI3, and D6.1A, we examined the localization of SHs in a rat liver. Although none of expressions of the proteins were observed in hepatic lobules of a normal liver, the hepatocytes reacting with the antibodies existed in the periportal lesion of severely injured liver treated with galactosamine. Using the antibody with magnetic beads (MACS), CD44+ cells were sorted from the galactosamine-treated livers and then cultured. The CD44+ cells could proliferate and form colonies, which are morphologically similar to SHs. Although hepatic marker genes were expressed in both sorted and cultured CD44+ cells, neither bile duct cell nor oval cell marker genes were detected by PCR. When cultured SHs were transplanted into congenic rat livers in combination with radiation and partial portal ligation, SHs were inserted into hepatic trabecules and proliferated.
To reconstruct hepatic organoids, we tried three different methods. (1)When SHs and NPCs were plated on collagen sponge, SHs could proliferate and expand to form a hepatic organoid in the sponge. The structure includes MHs with bile canaliculi, bile ducts, and capillary-like structures. Furthermore, we also observed that isolated human hepatic cells could form hepatic organoid in the sponge. (2)After SHs were cultured on two multiporous membranes until they formed large colonies, one membrane were stacked on the other membrane as cells faced each other. The stacked cells could differentiate into MHs with forming bile canalicular networks. (3)When both SH colonies and the connective tissues of the remnant after the hepatocyte isolation were cultured in the microgravity rotating culture system, a relatively large size of hepatic organoids was formed with a few weeks.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (117 results)

All 2005 2004 2003 2002 Other

All Journal Article (72 results) Book (1 results) Patent(Industrial Property Rights) (6 results) Publications (38 results)

  • [Journal Article] Hepatocyte transplantation for total liver repopulation (Review)2005

    • Author(s)
      Mizuguchi T, et al.
    • Journal Title

      Journal of Hepatobiliary Pancreatic Surgery In press

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Coordination of Bile Canalicular Contraction in Hepatic Organoid Reconstructed by Rat Small Hepatocytes and Nonparenchymal Cells2005

    • Author(s)
      Sudo R, et al.
    • Journal Title

      Annals of Biomedical Engineering In press

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hepatic organoid formation in collagen sponge of cells isolated from human liver2005

    • Author(s)
      Sugimoto S, et al.
    • Journal Title

      Tissue Engineering In press

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of cytochrome P450 enzymes in hepatic organoid reconstructed by rat small hepatocytes2005

    • Author(s)
      Miyamoto S, et al.
    • Journal Title

      Journal of Gastroenterology Hepatololgy In press

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Transient expression of laminin α1 chain in regenerating murine liver : Restricted localization of laminin chanins and nidogen-12005

    • Author(s)
      Kikkawa Y, et al.
    • Journal Title

      Experimental Cell Research 305

      Pages: 99-109

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hepatocyte transplantation for total liver repopulation2005

    • Author(s)
      Mizuguchi T, Mitaka T, Katsuramaki T, Hirata K.
    • Journal Title

      J Hepatobiliary Pancreat Surg (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Coordination of Bile Canalicular Contraction in Hepatic Organoid Reconstructed by Rat Small Hepatocytes and Nonparenchymal Cells2005

    • Author(s)
      Sudo R, Kohara H, Mitaka T, Ikeda M, Tanishita K.
    • Journal Title

      Ann Biomed Eng (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hepatic organoid formation in collagen sponge of cells isolated from human liver2005

    • Author(s)
      Sugimoto S, Harada K, Shiotani T, Ikeda S, Katsura N, Ikai I, Mzuguchi T, Hirata K, Yamaoka Y, Mitaka T.
    • Journal Title

      Tissue Engineering 11(3/4)(in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of cytochrome P450 enzymes in hepatic organoid reconstructed by rat small hepatocytes2005

    • Author(s)
      Miyamoto S, Hirata K, Sugimoto S, Harada K, Takeda H, Mitaka T.
    • Journal Title

      J Gastroenterol Hepatol (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Transient expression of laminin al chain in regenerating murine liver: Restricted localization of laminin chanins and nidogen-12005

    • Author(s)
      Kikkawa Y, Mochizuki Y, Miner JH, Mitaka T.
    • Journal Title

      Exp Cell Res 305

      Pages: 99-109

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hepatocyte transplantation for total liver repopulation (Review)2005

    • Author(s)
      Mizuguchi T, et al.
    • Journal Title

      Journal of Hepatobiliary Pancreatic Surgery (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Transient expression of laminin α1 chain in regenerating murine liver : Restricted localization of laminin chanins and nidogen-12005

    • Author(s)
      Kikkawa Y, et al.
    • Journal Title

      Experimental Cell Research (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Coordination of Bile Canalicular Contraction in Hepatic Organoid Reconstructed by Rat Small Hepatocytes and Nonparenchymal Cells2005

    • Author(s)
      Sudo R, et al.
    • Journal Title

      Annals of Biomedical Engineering (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Hepatic organoid formation in collagen sponge of cells isolated from human liver2005

    • Author(s)
      Sugimoto S, et al.
    • Journal Title

      Tissue Engineering (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Expression of cytochrome P450 enzymes in hepatic organoid reconstructed by rat small hepatocytes2005

    • Author(s)
      Miyamoto S, et al.
    • Journal Title

      Journal of Gastroenterology Hepatololgy (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Growth of hepatic angiomyolipoma indicating malignant potential2004

    • Author(s)
      Mizuguchi T, et al.
    • Journal Title

      Journal of Gastroenterology Hepatololgy 19

      Pages: 1328-1330

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] In vitro induction of adult hepatic progenitor cells into insulin-producing2004

    • Author(s)
      Nakajima-Nagata N, et al.
    • Journal Title

      Biochemical Biophysical Research Communication 318

      Pages: 529-534

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Serum hyaluronate level is useful for predicting subclinical liver dysfunction after hepatectomy2004

    • Author(s)
      Mizuguchi T, et al.
    • Journal Title

      World Journal of Surgery 28(10)

      Pages: 971-976

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Bile canalicular formation in hepatic organoid reconstructed by rat small hepatocytes and hepatic nonparenchymal cells2004

    • Author(s)
      Sudo R, et al.
    • Journal Title

      Journal of Cellular Physiology 199(2)

      Pages: 252-261

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] 肝臓の再生医学2004

    • Author(s)
      原田 啓介, 他
    • Journal Title

      顕微鏡 39(2)

      Pages: 88-90

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] モデリングとリモデリング2004

    • Author(s)
      柴田 智壽, 他
    • Journal Title

      Surgery Frontier 11(2)

      Pages: 73-75

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 外科領域における肝不全発症と予防対策 治療2004

    • Author(s)
      平田 公一
    • Journal Title

      臨床と研究 81

      Pages: 1866-1866

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 再灌流障害の機構とその対策2004

    • Author(s)
      桂巻 正, 他
    • Journal Title

      Surgery Frontier 11(3)

      Pages: 233-238

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Growth of hepatic angiomyolipoma indicating malignant potential2004

    • Author(s)
      Mizuguchi T, Katsuramaki T, Nobuoka T, Nishikage A, Oshima H, Kawasaki H, Kimura S, Satoh M, Hirata K.
    • Journal Title

      J Gastroenterol Hepatol 19

      Pages: 1328-1330

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] In vitro induction of adult hepatic progenitor cells into insulin-producing cells2004

    • Author(s)
      Nakajima-Nagata N, Sugai M, Sakurai T, Mitaka T, Katakai T, Yamato E, Miyazaki J, Tabata Y, Shimizu A.
    • Journal Title

      Biochem Biophys Res Commun 318

      Pages: 529-534

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Serum hyaluronate level is useful for predicting subclinical liver dysfunction after hepatectomy2004

    • Author(s)
      Mizuguchi T, Katsuramaki K, Nobuoka T, Kawamoto M, Oshima H, Kawasaki H, Kikuchi H, Shibata C, Hirata K.
    • Journal Title

      World J Surg 28(10)

      Pages: 971-976

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Bile canalicular formation in hepatic organoid reconstructed by rat small hepatocytes and hepatic nonparenchymal cells2004

    • Author(s)
      Sudo R, Mitaka T, Ikeda S, Sugimoto S, Harada K, Hirata K, Tanishita K, Mochizuki Y.
    • Journal Title

      J Cell Physiol 199(2)

      Pages: 252-261

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] In vitro induction of adult hepatic progenitor cells into insulin-producing cells2004

    • Author(s)
      Nakajima-Nagata N, et al.
    • Journal Title

      Biochemical Biophysical Research Communication 318

      Pages: 529-534

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Serum hyaluronate level is useful for predicting subclinical liver dysfuncion after hepatectomy2004

    • Author(s)
      Mizuguchi T, et al.
    • Journal Title

      World Journal of Surgery 28(10)

      Pages: 971-976

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 肝臓の再生医学2004

    • Author(s)
      原田啓介, 他
    • Journal Title

      顕微鏡 39(2)

      Pages: 88-90

    • Related Report
      2004 Annual Research Report
  • [Journal Article] モデリングとリモデリング2004

    • Author(s)
      柴田智壽, 他
    • Journal Title

      Surgery Frontier 11(2)

      Pages: 73-75

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 外科領域における肝不全発症と予防対策 治療2004

    • Author(s)
      平田公一
    • Journal Title

      臨床と研究 81

      Pages: 1866-1866

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 再灌流障害の機構とその対策2004

    • Author(s)
      桂巻正, 他
    • Journal Title

      Surgery Frontier 11(3)

      Pages: 233-238

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Rapid formation of hepatic organoid in collagen sponge by rat small hepatocytes and hepatic nonparenchymal cells2003

    • Author(s)
      Harada K, et al.
    • Journal Title

      Journal of Hepatology 39(11)

      Pages: 716-723

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Apoptosis and necrosis after warm ischemia-reperfusion injury of the pig liver and their inhibition by ONO-17142003

    • Author(s)
      Meguro M, et al.
    • Journal Title

      Transplantation 75(5)

      Pages: 703-710

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Preoperative estimation of risk in hepatectomy using technetium-99m-galactosyl human serum albumin receptor amount by nonlinear 3-compartment model.2003

    • Author(s)
      Katsuramaki T, et al.
    • Journal Title

      Hepatogastroenterology 50(49)

      Pages: 174-177

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Role of inducible nitric oxide synthase in pig liver transplantation2003

    • Author(s)
      Kimura, H et al.
    • Journal Title

      Journal of Surgical Research 111(1)

      Pages: 28-37

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Successful ex vivo normothermic liver perfusion with purely artificial products using artificial blood2003

    • Author(s)
      Nui A, et al.
    • Journal Title

      Int J Artif Organs 26

      Pages: 46-52

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Tumor necrosis factor-a and IL-6 reduce bile canalicular contractions of rat hepatocytes2003

    • Author(s)
      Ikeda S, et al.
    • Journal Title

      Surgery 133(1)

      Pages: 101-109

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] In Vitroにおける肝組織形成2003

    • Author(s)
      三高 俊広, 他
    • Journal Title

      最新医学 58(3)

      Pages: 708-718

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 肝幹細胞研究の現状〜小型肝細胞〜2003

    • Author(s)
      杉本 真一, 他
    • Journal Title

      肝胆膵 46(3)

      Pages: 327-333

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of laminin chains by central neurons : analysis with gene and protein trapping techniques2003

    • Author(s)
      Yin Y, et al.
    • Journal Title

      Genesis 36(2)

      Pages: 114-127

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Opposing roles of integrin alpha6beta1 and dystroglycan in laminin-medated extracellular signal-regulated kinase activation2003

    • Author(s)
      Ferletta M, et al.
    • Journal Title

      Molecular and Biological Cell 14(5)

      Pages: 2088-2103

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mesangial cells organize the glomerular capillaries by adhering to the G domain of laminin alpha5 in the glomerular basement membrane2003

    • Author(s)
      Kikkawa Y, et al.
    • Journal Title

      Journal of Cell Biology 161(1)

      Pages: 187-196

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Rapid formation of hepatic organoid in collagen sponge by rat small hepatocytes and hepatic nonparenchymal cells2003

    • Author(s)
      Harada K, Mitaka T, Miyamoto S, Sugimoto S, Takeda H, Mochizuki Y, Hirata K.
    • Journal Title

      J Hepatology 39(5)

      Pages: 716-723

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Apotosis and necrosis after warm ischemia-reperfusion injury of the pig liver and their inhibition by ONO-17142003

    • Author(s)
      Meguro M, Katsuramaki T, Kimura H, Isobe M, Nagayama M, Kukita K, Nui A, Hirata K.
    • Journal Title

      Transplantation 75

      Pages: 703-710

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Preoperative Estimation of Risk in Hepatectomy Using Technetium-99m-Galactosyl Human Serum Albumin Receptor Amount by Nonlinear 3-Compartment Model2003

    • Author(s)
      Katsuramaki T, Fujimori K, Furuhata T, Kimura Y, Meguro M, Nagayama M, Honma H, Mukaiya M, Hareyama M, Hirata K.
    • Journal Title

      Hepato-Gastroenterology 50

      Pages: 174-177

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The role of inducible nitric oxide synthase in pig liver transplantation2003

    • Author(s)
      Kimura H, Katsuramaki T, Isobe M, Nagayama N, Meguro M, Kukita K, Nui A, Hirata K.
    • Journal Title

      J Surg Res 111

      Pages: 28-37

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of laminin chains by central neurons: analysis with gene and protein trapping techniques2003

    • Author(s)
      Yin Y, Kikkawa Y, Mudd JL, Skarnes WC, Sanes JR, Miner JH.
    • Journal Title

      Genesis 36(2)

      Pages: 114-27

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Opposing roles of integrin alpha6Abetal and dystroglycan in laminin-mediated extracellular signal-regulated kinase activation2003

    • Author(s)
      Ferletta M, Kikkawa Y, Yu H, Talts JF, Durbeej M, Sonnenberg A, Timpl R, Campbell KP, Ekblom P, Genersch E.
    • Journal Title

      Mol Biol Cell 14(5)

      Pages: 2088-103

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mesangial cells organize the glomerular capillaries by adhering to the G domain of laminin alphas in the glomerular basement membrane2003

    • Author(s)
      Kikkawa Y, Virtanen I, Miner JH.
    • Journal Title

      J Cell Biol 161(1)

      Pages: 187-96

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Successful ex vivo normothermic liver perfusion with purely artificial products using artificial blood2003

    • Author(s)
      Nui A, Katsuramaki T, Nagayama M, Meguro M, Kimura H, Isobe M, Hir to K.
    • Journal Title

      Int J Artif Organs 26

      Pages: 46-52

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Tumor necrosis factor-a and IL-6 reduce bile canalicular contractions of rat hepatocytes2003

    • Author(s)
      Ikeda S, Mitaka T, Harada K, Sato F, Mochizuki Y, Hirata K.
    • Journal Title

      Surgery 133(1)

      Pages: 101-109

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Morphological changes induced by extracellular matrix are correlated with maturation of rat small hepatocytes2002

    • Author(s)
      Sugimoto S, et al.
    • Journal Title

      J Cell Biochem 87(1)

      Pages: 16-28

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Prediction of graft viability from non-heart-beating donor pigs using hepatic microdialysate hypoxanthine levels.2002

    • Author(s)
      Nagayama M, et al.
    • Journal Title

      J Surg Res 107

      Pages: 210-218

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Proliferation of rat small hepatocytes after long-term cryopreservation.2002

    • Author(s)
      Ikeda S, et al.
    • Journal Title

      J.Hepatology 37(1)

      Pages: 7-14

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Immediate early genes and p21 regulation in liver of rats with acute hepatic failure2002

    • Author(s)
      Hui TT, et al.
    • Journal Title

      Am J Surg 183

      Pages: 457-463

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A novel inhibitor of inducible nitric oxid synthase (ONO-1714) prevents critical warm ischemia-reperfusion injury in the pig liver2002

    • Author(s)
      Meguro M, et al.
    • Journal Title

      Transplantation 73

      Pages: 1439-1446

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Long-Term Culture of Primary Human Hepatocytes with Preservation of Proliferative Capacity and Differentiated Functions2002

    • Author(s)
      Katsura N, et al.
    • Journal Title

      J Surg Res 106(1)

      Pages: 115-123

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Glycerol Suppresses Proliferation of Rat Hepatocytes and Human HepG2 Cells2002

    • Author(s)
      Sugiyama N, et al.
    • Journal Title

      J Surg Res 103

      Pages: 236-242

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Changes in the serum levels of apolipoprotein A-1 as an indicator of protein metabolism after hepatectomy2002

    • Author(s)
      Katsuramaki T, et al.
    • Journal Title

      Wound Rep Reg 10

      Pages: 77-82

    • NAID

      10010847167

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of bone marrow stromal cells on the structural and functional polarity of primary rat heptocytes2002

    • Author(s)
      Mizuguchi T, et al.
    • Journal Title

      In Vitro Cell Dev Biol 38(2)

      Pages: 62-65

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Morphological changes induced by extracellular matrix are correlated with maturation of rat small hepatocytes2002

    • Author(s)
      Sugimoto S, Mitaka T, Ikeda S, Harada K, Ikai I, Yamaoka Y, Mochizuki Y.
    • Journal Title

      J Cell Biochem 87(1)

      Pages: 16-28

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A novel inhibitor of inducible nitric oxid synthase (ONO-1714) prevents critical warm ischemia-reperfusion injury in the pig liver2002

    • Author(s)
      Meguro M, Katsuramaki T, Nagayama, M Kimura H, Isobe M, Kimura Y, Matsuno T, Nui A, Hirata H.
    • Journal Title

      Transplantation 73

      Pages: 1439-1446

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Long-Term Culture of Primary Human Hepatocytes with Preservation of Proliferative Capacity and Differentiated Functions2002

    • Author(s)
      Katsura N, Ikai I, Mitaka T, Shiotani T, Matsushita T, Yamanokuchi S, Sugimoto S, Kanazawa A, Terajima H, Mochizuki Y, Yamaoka Y.
    • Journal Title

      J Surg Res 106(1)

      Pages: 115-123

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Glycerol Suppresses Proliferation of Rat Hepatocytes and Human HepG2 Cells2002

    • Author(s)
      Sugiyama N, Mizuguchi T, Aoki T, Hui T, Inderbitzin D, Demetriou AA, Rozga J.
    • Journal Title

      J Surg Res 103

      Pages: 236-242

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Changes in the serum levels of apolipoprotein A-1 as an indicator of protein metabolism after hepatectomy2002

    • Author(s)
      Katsuramaki T, Hirata K, Kimura Y, Nagayama M, Meguro M, Kimura H, Honma T, Furuhata T, Ura H, Hata F, Mukaiya M.
    • Journal Title

      Wound Rep Reg 10

      Pages: 77-82

    • NAID

      10010847167

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of bone marrow stromal cells on the structural and functional polarity of primary rat heptocytes2002

    • Author(s)
      Mizuguchi T, Palm K, Hui T, Aoki T, Mochizuki Y, Mitaka T, Demetriou AA, Rozga J.
    • Journal Title

      In Vitro Cell Dev Biol 38(2)

      Pages: 62-65

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Prediction of graft viability from non-heart-beating donor pigs using hepatic microdialysate hypoxanthine levels2002

    • Author(s)
      Nagayama M, Katsuramaki T, Kimura H, Isobe M, Meguro M, Matsuno T, Nui A, Hirata K.
    • Journal Title

      J Surg Res 107

      Pages: 210-218

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Proliferation of rat small hepatocytes after long-term cryopreservation2002

    • Author(s)
      Ikeda S, Mi aka T, Sugimoto S, Harada K, Mochizuki Y.
    • Journal Title

      Hepatology 37(1)

      Pages: 7-14

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Demetriou AA. Immediate early genes and p21 regulation in liver of rats with acute hepatic failure2002

    • Author(s)
      Hui TT, Mizuguchi T, Sugiyama N, Avital I, Rozga J
    • Journal Title

      Am J Surg 183

      Pages: 457-463

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Reconstruction of hepatic organoid by hepatic stem cells2002

    • Author(s)
      Mitaka T.
    • Journal Title

      J Hepatobiliary Pancreat Surg 9(6)

      Pages: 697-703

    • NAID

      10015744344

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 消化器外科学レビュー20042004

    • Author(s)
      桂巻正, 他
    • Publisher
      総合医学社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] ヒアルロン酸を用いた小型肝細胞の選択的培養法及び分離法2004

    • Inventor(s)
      三高 俊広
    • Industrial Property Rights Holder
      科学技術振興機構
    • Industrial Property Number
      2004-191477
    • Filing Date
      2004-06-29
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 特異的抗体を用いる小型肝細胞の分離法2004

    • Inventor(s)
      三高 俊広
    • Industrial Property Rights Holder
      科学技術振興機構
    • Industrial Property Number
      2004-191476
    • Filing Date
      2004-06-29
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 細胞培養用坦体2004

    • Inventor(s)
      三高 俊広
    • Industrial Property Rights Holder
      科学技術振興機構
    • Industrial Property Number
      2004-133006
    • Filing Date
      2004-04-28
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 細胞培養法、細胞の三次元培養法、三次元組織及び人工臓器2003

    • Inventor(s)
      須藤 亮
    • Industrial Property Rights Holder
      慶應大学
    • Industrial Property Number
      2003-038567
    • Filing Date
      2003-11-14
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 繊維化抑制剤2003

    • Inventor(s)
      平田 公一, 桂巻 正
    • Industrial Property Rights Holder
      平田 公一, 桂巻 正
    • Industrial Property Number
      2003-279360
    • Filing Date
      2003
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 肝組織誘導に適した小型肝細胞高含有コロニー、その調整2002

    • Inventor(s)
      三高 俊広, 他
    • Industrial Property Rights Holder
      北海道TLO
    • Filing Date
      2002-04-12
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Shinichiro Ikeda, et al.: "Tumor necrosis factor-α and IL-6 reduce bile canalicular contractions of rat hepatocytes"Surgery. 133(1). 101-109 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Atsushi Takamura, et al.: "Accumulation of Hsp70/Hsc70 molecular chaperone regulator BAG-1 on COPI-coated structures in gastric epithelial cells"International Journal of Oncology. 23(5). 1301-1308 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Keisuke Harada, et al.: "Rapid formation of hepatic organoid in collagen sponge by rat small hepatocytes and hepatic nonparenchymal cells"Journal of Hepatology. 39(11). 716-723 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 三高 俊広, 他: "In Vitroにおける肝組織形成"最新医学. 58(3). 708-718 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 杉本 真一, 他: "肝幹細胞研究の現状〜小型肝細胞〜"肝胆膵. 46(3). 327-333 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yin Y, et al.: "Expression of laminin chains by central neurons : analysis with gene and protein trapping techniques"Genesis. 36(2). 114-127 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ferletta M, et al.: "Opposing roles of integrin alpha6betal and dystroglycan in laminin-mediated extracellular signal-regulated kinase activation"Molecular and Biological Cell. 14(5). 2088-2103 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamato Kikkawa, et al.: "Mesangial cells organize the glomerular capillaries by adhering to the G domain of laminin alpha5 in the glomerular basement membrane"Journal of Cell Biology. 161(1). 187-196 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yasutoshi Kimura, et al.: "Frequent beta-catenin alteration in gallbladder carcinomas"Journal of Experimental Clinical Cancer Research. 22(2). 321-328 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] H.Tanaka, et al.: "Differential gene expression screening between parental and highly metastatic pancreatic cancer variants using a DNA microarray"Journal of Experimental Clinical Cancer Research. 22(2). 307-313 (2003)

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      2003 Annual Research Report
  • [Publications] Masayo Kawakami, et al.: "Expression analysis of vascular endothelial growth factors and their relationships to lymph node metastasis in human colorectal cancer"Journal of Experimental Clinical Cancer Research. 22(2). 229-237 (2003)

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      2003 Annual Research Report
  • [Publications] Hitoshi Kimura, et al.: "Role of inducible nitric oxide synthase in pig liver transplantation"Journal of Surgical Research. 111(1). 28-37 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Masayo Kawakami, et al.: "Quantification of vascular endothelial growth factor-C and its receptor-3 messenger RNA with real-time quantitative polymerase chain reaction as a predictor of lymph node metastasis in human colorectal cance"Surgery. 133(3). 300-308 (2003)

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      2003 Annual Research Report
  • [Publications] Hiroomi Tatsuumi, et al.: "Surgical influence on TH1/TH2 balance and monocyte surface antigen expression and its relation to infectious complications"World Journal of Surgery. 27(5). 522-528 (2003)

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      2003 Annual Research Report
  • [Publications] Makoto Meguro, et al.: "Apoptosis and necrosis after warm ischemia-reperfusion injury of the pig liver and their inhibition by ONO-1714"Transplantation. 75(5). 703-710 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yasutoshi Kimura, et al.: "Traumatic transection of the pancreas head : report of a case with santorini duct injury treated by damage-control surgery"Pancreas. 26(2). 205-207 (2003)

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  • [Publications] Akihiro Nui, et al.: "Successful ex vivo normothermic liver perfusion with purely artificial products using artificial blood"International Journal of Artificial Organ. 26(1). 46-52 (2003)

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  • [Publications] Tomohisa.Furuhata, et al.: "Efficacy of SPIO-MR imaging in the diagnosis of liver metastases from colorectal carcinomas"Diagnostic Surgery. 20(4). 321-325 (2003)

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  • [Publications] Tadashi Katsuramaki, et al.: "Preoperative estimation of risk in hepatectomy using technetium-99m-galactosyl human serum albumin receptor amount by nonlinear 3-compartment model"Hepatogastroenterology. 50(49). 174-177 (2003)

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  • [Publications] 原田 啓介, 他: "肝臓の再生医学"顕微鏡. (印刷中). (2004)

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  • [Publications] Ryo Sudo, et al.: "Bile canalicular formation in hepatic organoid reconstructed by rat small hepatocytes and hepatic nonparenchymal cells"Journal of Cellular Physiology. (in press). (2004)

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  • [Publications] 三高 俊広: "動き出した再生医療の臨床 〜肝臓〜"分子細胞治療. 1(1). 78-85 (2002)

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  • [Publications] Mizuguchi T, 他7名: "Effects of bone marrow stromal cells on the structural and functional polarity of primary rat heptocytes"In Vitro Cellular & Developmental Biology. 38(2). 62-65 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Katsura N, 他9名: "Long Term Culture of Primary Human Hepatocytes with Preservation of Proliferative Capacity and Differentiated Functions"Journal of Surgical Research. 106(1). 115-123 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ikeda S, 他4名: "Proliferation of rat small hepatocytes after long-term cryopreservation"Journal of Hepatology. 37(1). 7-14 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Manase K, 他8名: "The significance of membrane type 1 metalloproteinase in structural involution of human corpora lutea"Molecular Human Reproduction. 8(8). 742-749 (2002)

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  • [Publications] Sugimoto S, 他6名: "Morphological changes induced by extracellular matrix are correlated with maturation of rat small hepatocytes"Journal of Cellular Biochemistry. 87(1). 16-28 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nagayama M, 他7名: "Prediction of graft viability from non-heart-beating donor pigs using hepatic microdialysate hypoxanthine levels"Journal of Surgical Research. 107(2). 210-218 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Meguro M, 他8名: "A novel inhibitor of inducible nitric oxid synthase (ONO-1714) prevents critical warm ischemia-reperfusion injury in the pig"Transpiantation. 73(9). 1439-1446 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Katsuramaki T, 他9名: "Changes in the serum levels of apolipoprotein A-1 as an indicator of protein metabolism after hepatectomy"Wound Repair Regen. 10(1). 77-82 (2002)

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  • [Publications] 平田公一, 他2名: "肝左葉切除"消化器外科. 25. 1069-1078 (2002)

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  • [Publications] Nui A, 他8名: "Successful ex vivo normothermic liver perfusion with purely artificial products using artificial blood"International Journal of Artificial Organs. 26(1). 46-52 (2002)

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  • [Publications] Araya J, 他7名: "The regulation of KGF and TGF-beta by an angiotensin II type 1 receptor antagonist in hepatic ischemia-reperfusion injury"Transplantation Proceedings. 35(1). 107-110 (2002)

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  • [Publications] Ikeda s, 他5名: "Tumor necrosis factor-a and IL-6 reduce bile canalicular contractions of rat hepatocytes"Surgery. 133(1). 101-109 (2003)

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      2002 Annual Research Report
  • [Publications] Mitaka T: "Reconstruction of hepatic organoid by hepatic stem cells"Journal of Hepatobiliary Pancreatic Surgery. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 三高俊広, 他2名: "In Vitroにおける肝組織形成"最新医学. 58(3)(印刷中). (2003)

    • Related Report
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  • [Publications] 杉本真一, 他2名: "肝幹細胞研究の現状 〜小型肝細胞〜"肝胆膵. 46(3)(印刷中). (2003)

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  • [Publications] 桂巻 正, 他2名: "専門医のための消化器外科学レビュー2002"虚血再灌流障害(NOとフルーラジカル). 72-77 (2002)

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Published: 2002-04-01   Modified: 2016-04-21  

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