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Preclinical study in hapatocyte transplantation and regeneration of liver tissue

Research Project

Project/Area Number 18390351
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionNara Medical University

Principal Investigator

NAKAJIMA Yoshiyuki  Nara Medical University, 医学部, 教授 (00142381)

Co-Investigator(Kenkyū-buntansha) OHASHI Kazuo  奈良県立医科大学, 医学部, 助教 (40364062)
SHIBATA Masaru  奈良県立医科大学, 医学部, 助教 (50405388)
Project Period (FY) 2006 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥17,480,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥2,280,000)
Fiscal Year 2008: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2007: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2006: ¥7,600,000 (Direct Cost: ¥7,600,000)
Keywords移植外科学 / 肝不全 / 肝細胞 / 血友病 / 肝細胞移植 / 組織工学 / 細胞治療 / 前臨床実験 / 再生医療
Research Abstract

肝不全治療としての肝臓移植に代わる治療として, 肝細胞移植に関する研究を行い, 肝臓外への肝組織構築の実現化に向けた研究を行った. 特に新たな組織工学的手法を用いて, culture dishの上で2次元, 3次元肝細胞シートを作成し, マウス皮下に「場」を確保し, 移植した. その結果, 皮下からの血管新生が促進され, 細胞が安定して肝細胞としての機能を保持したままで, マウスの皮下に長期間生着させることに世界で初めて成功した. 組織学的あるいは血清中のアルブミンや血液凝固因子の解析から肝機能が維持される事を明らかとした. 同時に再生能力を有する事も明らかとなった. この効果は200日以上にわたり, 維持される事が判明し, これまでに報告のない研究成果となった. 肝臓が作るタンパク質等の物質のうち, 比較的少量でも人体に十分である血友病などにおいては, その臨床効果は十分にあると予想される.

Report

(4 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (16 results)

All 2008 2007 2006

All Journal Article (14 results) (of which Peer Reviewed: 4 results) Presentation (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Therapeutic effects of hepatocyte transplantation on hemophilia B2008

    • Author(s)
      Tatsumi K, Ohashi K, Shima M, Nakajima Y, Okano T, Yoshioka A
    • Journal Title

      Transplantation 86(1)

      Pages: 167-70

    • Related Report
      2008 Final Research Report
  • [Journal Article] Establishment of embryonic stem cells secreting human factor VIII for cell-based treatment of hemophilia A2008

    • Author(s)
      Kasuda S, Kubo A, Sakurai Y, Irion S, Ohashi K, Tatsumi K, Nakajima Y, Saito Y, Hatake K, Pipe SW, Shima M, Yoshioka A
    • Journal Title

      J Thromb Haemost 6(8)

      Pages: 1352-9

    • Related Report
      2008 Final Research Report
  • [Journal Article] Successful in vivo propagation of factor IX-producing hepatocytes in mice : potential for cell-based therapy in haemophilia B2008

    • Author(s)
      Tatsumi K, Ohashi K, Kataoka M, Tateno C, Shibata M, Naka H, Shima M, Hisanaga M, Kanehiro H, Okano T, Yoshizato K, Nakajima Y, Yoshioka A
    • Journal Title

      Thromb Haemost 99(5)

      Pages: 883-91

    • Related Report
      2008 Final Research Report
  • [Journal Article] Therapeutic effects of hepatocyte transplantation on hemophilia B2008

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

      Transplantation 86

      Pages: 167-170

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Establishment of embryonic stem cells secreting human factor VIII for cell-based treatment of hemophilia A.2008

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

      J Thromb Haemost. 6

      Pages: 1352-1359

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Successful in vivo propagation of factor IX-producing hepatocytes in mice : potential for cell-based therapy in haemophilia B.2008

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

      Thromb Haemost 99

      Pages: 883-891

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Y. Engineering functional two- and three-dimensional liver systems in vivo using hepatic tissue sheets2007

    • Author(s)
      Ohashi K, Yokoyama T, Yamato M, Kuge H, Kanehiro H, Tsutsumi M, Amanuma T, Iwata H, Yang J, Okano T, Nakajima Y
    • Journal Title

      Nat Med 13(7)

      Pages: 880-5

    • Related Report
      2008 Final Research Report
  • [Journal Article] Engineering functional two-and three-dimensional liver systems in vivo using hepatic tissue sheets2007

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

      Nat Med 13

      Pages: 880-885

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Engineering functional two- and three-dimensional liver systems in vivo using hepatic tissue sheets2007

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

      Nature Medicine (In press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 肝細胞シートを用いた肝組織工学の新展開2007

    • Author(s)
      大橋一夫, 中島祥介
    • Journal Title

      医学のあゆみ 220/7

      Pages: 581-586

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Genetic modification of hepatocytes towards hepatocyte transplantation and liver tissue engineering.2006

    • Author(s)
      Kuge H, Ohashi K, Nakajima Y, et al.
    • Journal Title

      Cell Transplantation 15/1

      Pages: 1-12

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Survival of microencapsulated islets at 400 days posttransplantation in the omental pouch of NOD mice.2006

    • Author(s)
      Kobayashi T, Nakajima Y, et al.
    • Journal Title

      Cell Transplantation 15/4

      Pages: 359-364

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 肝再生医療-局所環境制御と細胞環境制御に重点をおいた新たなアプローチ2006

    • Author(s)
      大橋一夫, 他
    • Journal Title

      医学のあゆみ 218/2

      Pages: 149-154

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 肝ティッシュエンジニアリングにおける新展開-シート工学を応用した新規肝再生治療2006

    • Author(s)
      大橋一夫
    • Journal Title

      東京女子医科大学雑誌 76/1

      Pages: 36-41

    • Related Report
      2006 Annual Research Report
  • [Presentation] MRIからみた肝ティッシュエンジニアリングの機能的・構造的有用性2008

    • Author(s)
      大橋 一夫
    • Organizer
      第7回 日本再生医療学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2008-03-13
    • Related Report
      2007 Annual Research Report
  • [Patent(Industrial Property Rights)] 血友病B治療剤及びその製造方法2006

    • Inventor(s)
      大橋一夫, 他3名
    • Industrial Property Rights Holder
      広島県産業科学技術研究所, 他
    • Filing Date
      2006-08-17
    • Related Report
      2006 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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