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Development of hybrit mouse with humanized liver using superfreezing preserved human small hepatocytes.

Research Project

Project/Area Number 20591615
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

MIZUGUCHI Toru  Sapporo Medical University, 医学部, 准教授 (30347174)

Co-Investigator(Kenkyū-buntansha) HIRATA Koichi  札幌医科大学, 医学部, 教授 (50136959)
MITAKA Toshihiro  札幌医科大学, 医学部, 教授 (50231618)
NAGAYAMA Minoru  札幌医科大学, 医学部, 助教 (40398326)
MEGURO Makoto  札幌医科大学, 医学部, 助教 (50448601)
SHIBATA Toshihito  札幌医科大学, 医学部, 研究員 (80404622)
KAJI Shinsuke  札幌医科大学, 医学部, 研究員 (90404623)
KAWAMOTO Masaki  札幌医科大学, 医学部, 助教 (70404605)
NAKAMURA Yukio  札幌医科大学, 医学部, 研究員 (50516648)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords自己組織化 / 生体機能利用 / 移植・再生医療 / 応用動物 / 再生医学
Research Abstract

It is very important to perform surgical operation to obtain cell donation for cell transplantation therapy. Conventional hepatectomy has been considered to be difficult to decrease high mobidity with mortlity. A saline-linked electiric cautery was very effective to achieve vessel sealing and decrease bleeding. In addition, recovery of postoperative Apo-B in this group was much faster than conventional hepatectomy (Hepatogastroenterology 2008 ; 55 : 2188-2192.). Gene transduction of Pdx-1 could transform small hepatocyte into insulin, glucagon, and somatostatine producing cells. Furthermore, small hepatocytes tend to be trans-differentiated into beta cells and mature hepatocytes tend to be trans-differentiated into alpha cells after transduction of Pdx-1 gene (J Hepatobiliary Pancreat Surg 2008 ; 15 : 403-409.). On the other hand, urinary trypsin inhibitor (UTI) is one of the proteins which the liver could produce by itself exclusively. The liver regeneration has been impaired in UTI deficient animals (Liver Int 2009 ; 29 : 979-987.). The gene expression could be depending on host conditions and human races. So, we compared gene expressions using micro DNA array analysis among Japanese patients and Finn patients (Genes Chromosomes Cancer 2010; 49: 28-39.). We proved all above research results and presented the data in both national and international congresses. We also discuss each other to promote further collaboration in future.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (34 results)

All 2011 2010 2009 2008 Other

All Journal Article (17 results) (of which Peer Reviewed: 16 results) Presentation (13 results) Book (2 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Laparoscophepatectomy : a systematic review, meta-analysis and power analysis.2011

    • Author(s)
      Mizuguchi T, Kawamoto M, Meguro M, Shibata T, Nakamura Y, Sonoda T, Hirata K.
    • Journal Title

      Surg Today 41

      Pages: 39-47

    • NAID

      10027818558

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Laparoscopic hepatectomy : a systematic review, meta-analysis, and power analysis.2011

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

      Surg Today

      Volume: 41 Pages: 39-47

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Karjalainen-Lindsberg ML, Puolakkainen P, Monni O. Gene expression analysis identifies over-expression of CXCL1, SPARC, SPP1, and SULF1 in gastric cancer.2010

    • Author(s)
      Junnila S, Kokkola A, Mizuguchi T, Hirata K,
    • Journal Title

      Genes Chromosomes Cancer 49

      Pages: 28-39

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Gene expression analysis identifies over-expression of CXCL1, SPARC, SPP1, and SULF1 in gastric cancer2010

    • Author(s)
      Junnila S, Kokkola A, Mizuguchi T, et al.
    • Journal Title

      Genes Chromosomes Cancer. 49

      Pages: 28-39

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical compliance with an oral uracil/tegafur (UFT) plus leucovorin (LV) regimen as adjuvant chemotherapy in Japanese colorectal cancer patients.2009

    • Author(s)
      Meguro M, Furuhata T, Okita K, Nishidate T, Mizuguchi T, Hirata K.
    • Journal Title

      Int J Clin Oncol 14

      Pages: 402-407

    • NAID

      10027200833

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Impaired liver regeneration with humoral and genetic disturbances in urinary trypsin inhibitor-deficient mice.2009

    • Author(s)
      Nobuoka T, Mizuguchi T, Oshima H, Shibata T, Kaji S, Nagayama M, Meguro M, Mitaka T, Hirata K.
    • Journal Title

      Liver Int 29

      Pages: 979-987

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic impact of surgical complications and preoperative serum hepatocyte growth factor in hepatocellular carcinoma patients after initial hepatectomy.2009

    • Author(s)
      Mizuguchi T, Nagayama M, Meguro M, Shibata T, Kaji S, Nobuoka T, Kimura Y, Furuhata T, Hirata K.
    • Journal Title

      J Gastrointest Surg 13

      Pages: 325-333

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Impaired liver regeneration with humoral and genetic disturbances in urinary trypsin inhibitor-deficient mice2009

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

      Liver Int. 29

      Pages: 979-987

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic impact of surgical complications and preoperative serum hepatocyte growth factor in hepatocellular carcinoma patients after initial hepatectomy.2009

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

      J Gastrointest Surg. 13(2)

      Pages: 325-333

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Laminin alpha 5 mediates ectopic adhesion of hepatocellular carcinoma through integrins and/or Lutheran/basal cell adhesion molecule.2008

    • Author(s)
      Kikkawa Y, Sudo R, Kon J, Mizuguchi T, Nomizu M, Hirata K, Mitaka T.
    • Journal Title

      Exp Cell Res 314

      Pages: 2579-2590

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Efficient transformation of small hepatocytes into insulin-expressing cells by forced expression of Pdx1.2008

    • Author(s)
      Kawasaki H, Mizuguchi T, Oshima H, Nobuoka T, Shibata T, Kaji S, Kokai Y, Katsuramaki T, Mitaka T, Hirata K.
    • Journal Title

      J Hepatobiliary Pancreat Surg 15

      Pages: 403-409

    • NAID

      10021948664

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] In vitro transformation of adult rat hepatic progenitor cells into pancreatic endocrine hormone.producing cells.2008

    • Author(s)
      Kawasaki H, Mizuguchi T, Kikkawa Y, Oshima H, Sasaki Y, Tokino T, Kokai Y, Miyazaki J, Katsuramaki T, Mitaka M, Hirata K.
    • Journal Title

      J Hepatobiliary Pancreat Surg 15

      Pages: 310-317

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Rapid recovery of postoperative liver function after major hepatectomy using saline-linked cautery.2008

    • Author(s)
      Mizuguchi T, Katsuramaki T, Nagayama M, Meguro M, Shibata T, Kaji S, Hirata K.
    • Journal Title

      Hepatogastroenterology 55

      Pages: 2188-2192

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Proliferation of hepatocyte progenitor cells isolated from adult human livers in serum-free medium.2008

    • Author(s)
      Sasaki K, Kon J, Mizuguchi T, Chen Q, Ooe H, Oshima H, Hirata K, Mitaka T.
    • Journal Title

      Cell Transplant 17

      Pages: 1221-1230

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Rapid recovery of postoperative liver function after major hepatectomy using saline-linked electric cautery.2008

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

      Hepatosastroenterology 55(88)

      Pages: 2188-2192

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic impact of preoperative branched-chain amino acids to the tyrosine ratio level in hepatocellular carcinoma patients after initial hepatectomy.

    • Author(s)
      Mizuguchi T, Kawamoto M, Meguro M, Nakamura Y, Hirata K.
    • Journal Title

      J Gastroint Surg in press

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Serum antithrombin III level is well correlated with multiple indicators for assessment of liver function and diagnostic accuracy for predicting postoperative liver failure in hepatocellular caccinoma patients.

    • Author(s)
      Mizuguchi T, Kawamoto M, Son S, Meguro M, Shibata T, Nakamura Y, Harada K, Furuhata T, Hirata K.
    • Journal Title

      Hepatogastroenterology in pres

    • Related Report
      2010 Final Research Report
  • [Presentation] Hirata KCluster analysis of liver functional indicators and ALB-BTR classification to predict postoperative prognosis in 165 HCC patients.2011

    • Author(s)
      Mizuguchi T, Kawamoto K, Meguro M, Nakamura Y, Harada K, Nobuoka T
    • Organizer
      6th Annual Academic Surgical Congress, Full oral presentation
    • Place of Presentation
      Huntington Beach, CA, USA
    • Related Report
      2010 Final Research Report
  • [Presentation] Cluster analysis of liver functional indicators and ALB-BTR classification to predict postoperative prognosis in 165 HCC patients.2011

    • Author(s)
      T.Mizuguchi, et al.
    • Organizer
      6^<th> Annual Academic Surgical Congress
    • Place of Presentation
      Huntington Beach, CA, USA
    • Related Report
      2010 Annual Research Report
  • [Presentation] 最善の肝切除術を目指した基本技術と新しい工夫2010

    • Author(s)
      水口徹, 川本雅樹、目黒誠、今村将史、信岡隆幸、平田公一
    • Organizer
      (主題関連演題)第72回日本臨床外科学会総会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report
  • [Presentation] 腹腔鏡下肝切除術は低侵襲と言えるのか-検出力解析からの検証2010

    • Author(s)
      水口徹, 川本雅樹、目黒誠、中村幸雄、西舘敏彦、沖田憲司、木村康利、古畑智久、平田公一
    • Organizer
      (ワークショップ)第23回日本内視鏡外科学会総会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report
  • [Presentation] 肝不全予測因子の多変量解析とクラスター解析による分類2010

    • Author(s)
      水口徹, 川本雅樹、目黒誠、今村将史、永山稔、木村康利、信岡隆幸、平田公一
    • Organizer
      (ミニシンポジウム)第22回日本肝胆膵外科学会・学術集会
    • Place of Presentation
      仙台
    • Related Report
      2010 Final Research Report
  • [Presentation] Easy techniques and procedures for laparoscopic hybrid liver resection : the introduction reading to complete laparoscopic hepatectomy.2009

    • Author(s)
      水口徹, 平田公一, 目黒誠, 川本雅樹, 永山稔, 今村将史, 木村康利, 古畑智久
    • Organizer
      The 43th World Congress of the International society of Surgery
    • Place of Presentation
      Video oral presentation, Adelade
    • Related Report
      2010 Final Research Report
  • [Presentation] 肝細胞癌初回肝切除時の肝予備能評価としてのATIIIおよびHGFの合併症予測因子および予後因子としての有用性に関する検討2009

    • Author(s)
      水口徹, 目黒誠, 孫誠一、川本雅樹、永山稔, 今村将史、木村康利, 信岡隆幸, 平田公一
    • Organizer
      (ワークショップ)第21回日本肝胆膵外科学会
    • Place of Presentation
      名古屋
    • Related Report
      2010 Final Research Report
  • [Presentation] Evaluation of anti-thrombin III and hepatocyte growth factor level to predict postoperative complication and disease-free survival in the initial liver resection for viral HCC patients.2009

    • Author(s)
      水口徹, 平田公一, 目黒誠, 永山稔, 古畑智久, 信岡隆幸, 山口浩司
    • Organizer
      4th Annual academic surgical congress
    • Place of Presentation
      Fort Myers, FL, USA
    • Related Report
      2010 Final Research Report
  • [Presentation] Easy techniques and procedures for laparoscopic hybrid liver resection : the introduction reading to complete laparoscopic hepatectomy2009

    • Author(s)
      T.Mizuguchi, et al.
    • Organizer
      The 43th World Congress of the International society of Surgery
    • Place of Presentation
      Adelade, Australia
    • Related Report
      2009 Annual Research Report
  • [Presentation] Evaluation of anti-thrombin III and hepatocyte growth factor level to predict postoperative complication and disease-free survival in the initial liver resection for viral HCC patients.2009

    • Author(s)
      Mizuguchi T, et al.
    • Organizer
      4^<th> Annual Academic Surgical Congress
    • Place of Presentation
      Fort Myers, Florida
    • Related Report
      2008 Annual Research Report
  • [Presentation] 腹腔鏡下肝切除術の安全性の確保と標準化への挑戦2008

    • Author(s)
      水口徹, 平田公一、目黒誠, 河野剛、永山稔, 信岡隆幸, 木村康利, 古畑智久、山口浩司
    • Organizer
      (スポンサードシンポジウム)第21回日本内視鏡外科学会総会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report
  • [Presentation] 組織幹細胞を用いた肝再生医療の可能性2008

    • Author(s)
      平田公一, 水口徹, 大島秀紀, 佐々木寿誉, 三高俊広
    • Organizer
      (後教育セミナー)第108回日本外科学会定期学術集会
    • Place of Presentation
      長崎
    • Related Report
      2010 Final Research Report
  • [Presentation] 肝再生機序の解明への挑戦. プロメテウス神話から臨床治療までの道2008

    • Author(s)
      水口徹, 平田公一、永山稔, 目黒誠, 川崎浩之、信岡隆幸, 木村康利, 山口浩司, 古畑智久, 三高俊広
    • Organizer
      (アカデミックマインドの涵養)第108回日本外科学会定期学術集会
    • Place of Presentation
      長崎
    • Related Report
      2010 Final Research Report
  • [Book] 多臓器損傷. 腹腔鏡下肝切除術(金子弘真、若林 剛編集)2010

    • Author(s)
      水口徹、平田公一
    • Publisher
      南山堂
    • Related Report
      2010 Final Research Report
  • [Book] 腹腔鏡下肝切除術2010

    • Author(s)
      水口徹、平田公一
    • Total Pages
      118
    • Publisher
      南山堂
    • Related Report
      2010 Annual Research Report
  • [Patent(Industrial Property Rights)] 結紮具および結紮方法2010

    • Inventor(s)
      水口徹、平田公一、川本雅樹、目黒誠
    • Industrial Property Rights Holder
      北海道公立大学法人 札幌医科大学
    • Industrial Property Number
      2010-226110
    • Filing Date
      2010-10-05
    • Related Report
      2010 Final Research Report
  • [Patent(Industrial Property Rights)] 結紮具および結紮方法2010

    • Inventor(s)
      水口徹, 他
    • Industrial Property Rights Holder
      札幌医科大学
    • Industrial Property Number
      2010-226110
    • Filing Date
      2010-10-05
    • Related Report
      2010 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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