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Development of liver-target therapy based on cellular modification technology

Research Project

Project/Area Number 21300180
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomedical engineering/Biological material science
Research InstitutionTokyo Women's Medical University

Principal Investigator

OHASHI Ohashi  東京女子医科大学, 医学部, 准教授 (40364062)

Co-Investigator(Kenkyū-buntansha) NAKAYAMA Masamichi  東京女子医科大学, 医学部, 講師 (00338980)
TATSUMI Kohei  東京女子医科大学, 医学部, 助教 (70555432)
Co-Investigator(Renkei-kenkyūsha) IWATA Hiroo  京都大学, 再生医科学研究所, 教授 (30160120)
MIZUGUCHI Hiroyuki  大阪大学, 薬学研究科, 教授 (50311387)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2011: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2010: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2009: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Keywords細胞・組織工学 / 再生医療 / 細胞治療 / 遺伝子治療 / 細胞表面修飾 / 免疫隔離
Research Abstract

The present study was conducted to establish two different approaches for modifying hepatocytes. First, HGF gene transduction was conducted to isolated hepatoytes in suspension. The study showed that transplantation of HGF-transduced hepatocytes in vivo resulted in significant higher engraftment due to protection from apoptotis that occur after being transplanted in vivo. Second, hepatocyte surface modification technology was established using PEG-lipids. This modification allows hepatocytes to being coated ultra-thin polymer complexes.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (63 results)

All 2012 2011 2010 2009

All Journal Article (28 results) (of which Peer Reviewed: 22 results) Presentation (28 results) Book (5 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Preserved liver-specific functions of hepatocytes in 3D co-culture with endothelial cell sheets2012

    • Author(s)
      Kim K, Ohashi K, Utoh R, 他2名
    • Journal Title

      Biomaterials

      Volume: 33 Pages: 1406-1413

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The non-invasive cell surface modification of hepatocytes with PEG-lipid derivatives2012

    • Author(s)
      Tatsumi K, Ohashi K, Teramura Y, 他7名
    • Journal Title

      Biomaterials

      Volume: 33 Pages: 821-828

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Liver tissue engineering utilizing hepatocyte propagated in mouse livers in vivo2012

    • Author(s)
      Ohashi K, et al
    • Journal Title

      Cell Transplantation

      Volume: 21(in press) Issue: 2-3 Pages: 429-436

    • DOI

      10.3727/096368911x605330

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cell shape regulation based on hepatocyte sheet engineering technologies2012

    • Author(s)
      Takagi S, Ohno M, Ohashi K, et al
    • Journal Title

      Cell Transplantation

      Volume: 21(in press) Issue: 2-3 Pages: 411-420

    • DOI

      10.3727/096368911x605312

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 肝疾患再生医療-肝細胞シートを用いた組織工学2012

    • Author(s)
      大橋一夫
    • Journal Title

      GI Research

      Volume: 20 Pages: 57-63

    • Related Report
      2011 Annual Research Report
  • [Journal Article] ナノテクノロジーを基盤とした代謝系臓器の再生医療開発2012

    • Author(s)
      大橋一夫、岡野光夫
    • Journal Title

      遺伝子医学MOOK

      Volume: 20 Pages: 197-203

    • Related Report
      2011 Annual Research Report
  • [Journal Article] Production of islet cell sheet using cryopreserved islet cells2011

    • Author(s)
      Ohashi K, Mukobata S, Utoh R, 他4名
    • Journal Title

      Transplantation Proc

      Volume: 43 Pages: 3188-3191

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Reversal of diabetes by the creation of neo-islet tissues into a subcutaneous site using islet cell sheets2011

    • Author(s)
      Saito T, Ohashi K, Utoh R, 他6名
    • Journal Title

      Transplantation

      Volume: 92 Pages: 1231-1236

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Preserved liver-specific functions of hepatocytes in 3D co-culture with endothelial cell sheets2011

    • Author(s)
      Kim K, Ohashi K, et al
    • Journal Title

      Biomaterials

      Volume: 33 Issue: 5 Pages: 1406-1413

    • DOI

      10.1016/j.biomaterials.2011.10.084

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The non-invasive cell surface modification of hepatocytes with PEG-lipid derivatives2011

    • Author(s)
      Tatsumi K, Ohashi K, et al
    • Journal Title

      Biomaterials

      Volume: 33 Issue: 3 Pages: 821-828

    • DOI

      10.1016/j.biomaterials.2011.10.016

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Production of islet cell sheet using cryopreserved islet cells2011

    • Author(s)
      Ohashi K, et al
    • Journal Title

      Transplantation Proceedings

      Volume: 43 Issue: 9 Pages: 3188-3191

    • DOI

      10.1016/j.transproceed.2011.10.027

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hepatocyte transplantation through the hepatic vein.A new route of cell transplantation to the liver2011

    • Author(s)
      Goto Y, Ohashi K, et al
    • Journal Title

      Cell Transplantation

      Volume: 20 Issue: 8 Pages: 1259-1270

    • DOI

      10.3727/096368910x547417

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of coagulation factors from murine iPS-derived cells2011

    • Author(s)
      Kasuda S, Ohashi K, et al.
    • Journal Title

      Blood Coagulation and Fibrinolysis

      Volume: (in press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human hepatocyte propagation system in the mouse livers : functional maintenance of the production of_coagulation and anti-coagulation factors2011

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

      Cell Transplantation

      Volume: (in press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Engineering liver tissues under the kidney capsule site provides therapeutic effects to hemophilia B mice2010

    • Author(s)
      Ohashi K, Tatsumi K, Utoh R, 他3名
    • Journal Title

      Cell Transplantation

      Volume: 19 Pages: 807-813

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Engineering liver tissues under the kidney capsule sites provides therapeutic effects on hemophilia B2010

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

      Cell Transplantation

      Volume: 19 Pages: 807-813

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional life-long maintenance of engineered liver tissue in mice foliowing transplantation under the kidney capsule2010

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

      J Tissue Eng Reg Med

      Volume: 4 Pages: 141-148

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The homeobox gene HEX regulates hepatocyte differentiation from ES cell-derived endoderm.2010

    • Author(s)
      Kubo A, Ohashi K, et al.
    • Journal Title

      Hepatology

      Volume: 51 Pages: 533-541

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Engineering liver tissues under the kidney capsule sites provides therapeutic effects on hemophilia B2010

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

      Cell Transplantation (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Liver tissue engineering utilizing hepatocytes propagated in mouse livers in vivo2010

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

      Cell Transplantation (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human hepatocyte propagation system in the mouse livers : Functional maintenance of the production of coagulation and anti-coagulation factors2010

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

      Cell Transplantation (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cell shape regulation based on hepatocyte sheet engineering technologies2010

    • Author(s)
      Takagi S, Ohno M, Ohashi K, et al.
    • Journal Title

      Cell Transplantation (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 肝ティッシュエンジニアリングへのアプローチ:腎被膜下組織作製法とシート工学を用いた皮下肝組織作製法2010

    • Author(s)
      小山文一、大橋一夫, 他
    • Journal Title

      分子細胞フロンティア (In press)

    • Related Report
      2009 Annual Research Report
  • [Journal Article] 肝細胞移植と肝組織工学2010

    • Author(s)
      大橋一夫
    • Journal Title

      日本再生医療学会雑誌 9

      Pages: 53-59

    • Related Report
      2009 Annual Research Report
  • [Journal Article] 肝組織工学の開発と血友病治療への応用展開2010

    • Author(s)
      大橋一夫
    • Journal Title

      日本血栓止血学会雑誌 21

      Pages: 45-51

    • NAID

      10026118566

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Effects on coagulation factor production following primary hepatomitogen-induced direct hyperplasia2009

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

      World Journal of Gastroenterology 15

      Pages: 5307-5315

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bioengineering of a functional sheet of islet cells for the treatment of diabetes mellitus2009

    • Author(s)
      Shimizu H, Ohashi K, et al.
    • Journal Title

      Biomaterials 15

      Pages: 5943-5949

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 肝細胞を用いた再生医療の現状と展望2009

    • Author(s)
      大橋一夫
    • Journal Title

      次世代医療機器評価指標作製事業 再生医療(細胞シート)審査WG報告書

      Pages: 49-57

    • Related Report
      2009 Annual Research Report
  • [Presentation] In-animal propagation of hemophilic hepatocytes toward gene transduction and cell therapy2012

    • Author(s)
      Ohashi K
    • Organizer
      Workshop for novel therapies and gene transducti on for hemophilia
    • Place of Presentation
      Philadelphra, USA(招待講演)
    • Year and Date
      2012-03-01
    • Related Report
      2011 Annual Research Report
  • [Presentation] Engineering of liver tissues containing liver-specific non-parenchymal cells at the ectopic site2011

    • Author(s)
      Utoh R, Ohashi K, Okano T
    • Organizer
      Joint Congress of Cell Transplant Society and International Xenotransplantation Society
    • Place of Presentation
      Miami(USA)
    • Year and Date
      2011-10-25
    • Related Report
      2011 Final Research Report
  • [Presentation] In vivo propagation and genetic modification of hepatocytes toward gene and cell therapy2011

    • Author(s)
      Tatsumi K, Ohashi K, Tateno C, 他5名
    • Organizer
      Joint Congress of Cell Transplant Society and International Xenotransplantation Society
    • Place of Presentation
      Miami(USA)
    • Year and Date
      2011-10-25
    • Related Report
      2011 Final Research Report
  • [Presentation] Engineering of liver tissues containing various liver-specific non-parenchymal cells at ectopic site2011

    • Author(s)
      Utoh R, Ohashi K, et al
    • Organizer
      Cell Transplantation Society 2011 Annual Meeting
    • Place of Presentation
      Miami, USA
    • Year and Date
      2011-10-24
    • Related Report
      2011 Annual Research Report
  • [Presentation] Therapeutic islet tissue engineering in subcutaneous site with scaffold-free approaches2011

    • Author(s)
      Ohashi K, Saito T, Utoh R, 他5名
    • Organizer
      71th Scientific Sessions of American Diabetes Association
    • Place of Presentation
      San Diego(USA)
    • Year and Date
      2011-06-26
    • Related Report
      2011 Final Research Report
  • [Presentation] Fabrication of monolayered islet cell sheets from cryopreserved and dispersed islet cells2011

    • Author(s)
      Ohashi K, et al
    • Organizer
      International Pancreas and Islet Transplantation Association 2011 Meeting
    • Place of Presentation
      Praha, Czech
    • Year and Date
      2011-06-02
    • Related Report
      2011 Annual Research Report
  • [Presentation] Gene and cell therapy for hemophilia B using adipose tissue-derived stem/stromal cells transduced with a self-inactivating SIV lentivirus vector2011

    • Author(s)
      Watanabe N, Ohashi K, et al
    • Organizer
      2011 Annual Meeting, American Society of Gene and Cell Therapy
    • Place of Presentation
      Seattle, USA
    • Year and Date
      2011-05-21
    • Related Report
      2011 Annual Research Report
  • [Presentation] Construction of Liver-like Tissues Containing Hepatic Parenchymal And Non-parenchymal Cells in Mice with Chronic Liver Injury2010

    • Author(s)
      Utoh R, Ohashi K, et al.
    • Organizer
      61th Annual Meeting of the American Association for the Study of Liver Diseases
    • Place of Presentation
      Boston, USA
    • Year and Date
      2010-11-02
    • Related Report
      2010 Annual Research Report
  • [Presentation] Novel Approach for Cell and Gene Therapy of Hemophlia B Based on a Creation of Alter Ego2010

    • Author(s)
      辰巳公平、大橋一夫, 他
    • Organizer
      第72回日本血液学会学術集会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2010-09-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] Hepatocyte surface modification for liver regenerative medicine2010

    • Author(s)
      Tatsumi K, Ohashi K, Utoh R, 他3名
    • Organizer
      Tissue Engineering & Regenerative Medicine International Society 2010 Asia Pacific Meeting
    • Place of Presentation
      Sydey(Australia)
    • Year and Date
      2010-09-16
    • Related Report
      2011 Final Research Report
  • [Presentation] Cell sheet engineering toward bioengineering of functional neo-islets2010

    • Author(s)
      Ohashi K, Utoh R, Saito T, 他6名
    • Organizer
      Tissue Engineering & Regenerative Medicine International Society 2010 Asia Pacific Meeting
    • Place of Presentation
      Sydey(Australia)
    • Year and Date
      2010-09-16
    • Related Report
      2011 Final Research Report
  • [Presentation] Hepatocyte Surface Modification for Liver Regenerative Medicine2010

    • Author(s)
      Tatsumi K, Ohashi K, et al.
    • Organizer
      TERIS 201 Asia Pacific Meeting
    • Place of Presentation
      Sydney, Australia
    • Year and Date
      2010-09-16
    • Related Report
      2010 Annual Research Report
  • [Presentation] Cell Sheet Engineering Toward Bioengineering of Functional Neo-islets2010

    • Author(s)
      Ohashi K, et al.
    • Organizer
      TERIS 201 Asia Pacific Meeting
    • Place of Presentation
      Sydney, Australia
    • Year and Date
      2010-09-15
    • Related Report
      2010 Annual Research Report
  • [Presentation] Intelligent Surfaces for Cell Sheet Engineering2010

    • Author(s)
      Ohashi K, Teruo O
    • Organizer
      The 5^<th> GCOE International Symposium
    • Place of Presentation
      東京工業大学(招待講演)
    • Year and Date
      2010-09-10
    • Related Report
      2010 Annual Research Report
  • [Presentation] Hepatocyte Trnasplantation Through the Hepatic Vein : A New Route of Cell Transplantation to the Liver2010

    • Author(s)
      Goto Y, Ohashi K, et al.
    • Organizer
      XXIII International Congress of The Transplantation Society
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2010-08-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] Liver Tissue Engineering Using HGF-Transduced Hepatocytes Provides Therapeutic Effects on Lethal Liver Failure in Mice2010

    • Author(s)
      Ohashi K, et al.
    • Organizer
      XXIII International Congress of The Transplantation Society
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2010-08-16
    • Related Report
      2010 Annual Research Report
  • [Presentation] 肝病態下における肝細胞の増殖特性と再生医療への応用2010

    • Author(s)
      大橋一夫
    • Organizer
      第17回日本肝細胞研究会
    • Place of Presentation
      秋田アトリオン(招待講演)
    • Year and Date
      2010-06-19
    • Related Report
      2010 Annual Research Report
  • [Presentation] 肝細胞を基盤とした治療法-細胞移植から肝組織構築への展開2010

    • Author(s)
      大橋一夫
    • Organizer
      日本急性肝不全研究会
    • Place of Presentation
      山形テルサ(招待講演)
    • Year and Date
      2010-05-26
    • Related Report
      2010 Annual Research Report
  • [Presentation] 分離肝細胞の増殖制御と再生医療2010

    • Author(s)
      大橋一夫
    • Organizer
      日本再生医療学会
    • Place of Presentation
      広島県
    • Year and Date
      2010-03-19
    • Related Report
      2009 Annual Research Report
  • [Presentation] 分身化マウスの作製と細胞遺伝子治療への展開2010

    • Author(s)
      大橋一夫, 他
    • Organizer
      日本再生医療学会
    • Place of Presentation
      広島県
    • Year and Date
      2010-03-18
    • Related Report
      2009 Annual Research Report
  • [Presentation] ラット肝細胞シートを用いた同所性・異所性移植の検討2010

    • Author(s)
      朝長哲生、大橋一夫, 他
    • Organizer
      日本再生医療学会
    • Place of Presentation
      広島県
    • Year and Date
      2010-03-18
    • Related Report
      2009 Annual Research Report
  • [Presentation] 肝障害下における作製肝組織3次元化構築過程の解析2010

    • Author(s)
      鵜頭理恵、大橋一夫, 他
    • Organizer
      日本再生医療学会
    • Place of Presentation
      広島県
    • Year and Date
      2010-03-18
    • Related Report
      2009 Annual Research Report
  • [Presentation] Cell Sheet Engineering for Next Generation Regenerative Medicine2009

    • Author(s)
      Ohashi K
    • Organizer
      1^<st> International Conference Regenerative Surgery
    • Place of Presentation
      Rome, Italy
    • Year and Date
      2009-12-10
    • Related Report
      2009 Annual Research Report
  • [Presentation] Liver tissue engineering using HGF-transduced hepatocytes provides the rapeutic effects on lethal liver failure in mice2009

    • Author(s)
      Ohashi K, et al.
    • Organizer
      American Association for the Study of the Liver Disease 2009
    • Place of Presentation
      Boston, USA
    • Year and Date
      2009-11-02
    • Related Report
      2009 Annual Research Report
  • [Presentation] Hepatocyte engineering and tissue engineering for hemophilia2009

    • Author(s)
      Ohashi K
    • Organizer
      East Asia Hemophilia Forum
    • Place of Presentation
      Fukuoka, Japan
    • Year and Date
      2009-06-07
    • Related Report
      2009 Annual Research Report
  • [Presentation] Potential of HGF-transduced hepatocytes as a cell source for liver tissue engineering2009

    • Author(s)
      Ohashi K, et al.
    • Organizer
      American Society of Gene Therapy 12^<th> Annual Meeting
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2009-05-28
    • Related Report
      2009 Annual Research Report
  • [Presentation] A novel approach for autologous hepatocyte-based liver tissue engineering2009

    • Author(s)
      Ohashi K, et al.
    • Organizer
      International Conference of the Cell Transplantation Society
    • Place of Presentation
      Okayama, Japan
    • Year and Date
      2009-04-21
    • Related Report
      2009 Annual Research Report
  • [Presentation] Cell shape regulation based on hepatocyte sheet engineering technologies2009

    • Author(s)
      Takagi S, Ohashi K, et al.
    • Organizer
      International Conference of the Cell Transplantation Society
    • Place of Presentation
      Okayama, Japan
    • Year and Date
      2009-04-20
    • Related Report
      2009 Annual Research Report
  • [Book] 肝細胞の再生増殖と肝組織構築(治療)2010

    • Author(s)
      大橋一夫
    • Related Report
      2011 Final Research Report
  • [Book] 肝ティッシュエンジニアリングへのアプローチー腎被膜下組織作製法とシート工学を用いた皮下肝組織作製法分子細胞フロンティア2010

    • Author(s)
      小山文一、大橋一夫、岡野光夫, 他1名
    • Publisher
      外科分子細胞治療学会
    • Related Report
      2011 Final Research Report
  • [Book] 肝ティッシュエンジニアリング(みんなに役立つ血友病の基礎と臨床)2009

    • Author(s)
      大橋一夫
    • Publisher
      医薬ジャーナル社
    • Related Report
      2011 Final Research Report
  • [Book] 皮下に第二の肝臓を創る(治療学)2009

    • Author(s)
      大橋一夫
    • Related Report
      2011 Final Research Report
  • [Book] 肝細胞移植と肝組織工学の現状(医学のあゆみ)2009

    • Author(s)
      大橋一夫
    • Related Report
      2011 Final Research Report
  • [Patent(Industrial Property Rights)] 療用移植材料及びその利用方法2011

    • Inventor(s)
      大橋一夫, 他
    • Industrial Property Rights Holder
      東京女子医科大学
    • Filing Date
      2011-03-14
    • Related Report
      2010 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 治療用移植材料及びその利用方法2010

    • Inventor(s)
      大橋一夫、他
    • Industrial Property Rights Holder
      東京女子医科大学
    • Industrial Property Number
      2010-009542
    • Filing Date
      2010-03-31
    • Related Report
      2009 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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