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Reconstruction of human liver sheet for preclinical study of liver regenerative medicine

Research Project

Project/Area Number 23591868
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General surgery
Research InstitutionNagasaki University

Principal Investigator

EGUCHI Susumu  長崎大学, 医歯薬学総合研究科(医学系), 教授 (80404218)

Co-Investigator(Kenkyū-buntansha) KANEMATSU Takashi  長崎大学, 医歯薬学総合研究科(医学系), 名誉教授 (40128004)
Research Collaborator SAKAI Yusuke  長崎大学, 医歯薬学総合研究科(医学系), 助教 (10608904)
Project Period (FY) 2011-04-28 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords再生医療 / 肝臓 / 細胞シート / ヒト / 移植 / 肝細胞
Outline of Final Research Achievements

The liver regenerative medicine is extremely-difficult to establish, and the further research is looked forward to. In this study, we describe a novel liver regenerative medicine technology using reconstructed human liver sheet.
Human primary hepatocytes with more than 80 % of viability were isolated from surgical liver segment. Hepatocyte-only sheets were constructed by culturing it in suitable cell density. The engineered hepatocytes/fibroblast sheets (EHFSs) were constructed by culturing hepatocytes or HepaRG cells (well-differentiated hepatic cells derived from a human liver tumor) on a fibroblast. The EHFSs showed superior expression levels of vascularization-associated growth factors (VEGF, TGFb1, and HGF) in vitro. In addition, the EHFSs formed vascularized subcutaneous human liver tissues in mice. This technology could be expected as novel liver regenerative medicine technology.

Report

(5 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (42 results)

All 2015 2014 2013 2012 2011 Other

All Journal Article (15 results) (of which Peer Reviewed: 14 results,  Open Access: 1 results) Presentation (26 results) Book (1 results)

  • [Journal Article] Rapid fabrication of engineered liver tissue using novel fibroblast system2014

    • Author(s)
      Yusuke Sakai, Makiko Koike, Hideko Hasegawa, Kosho Yamanouchi, Akihiko Soyama, Masaaki Hidaka, Mitsuhisa Takatsuki, Tamotsu Kuroki, Teruo Okano, and Susumu Eguchi
    • Journal Title

      ALTEX Proceedings

      Volume: 3 Pages: 44-44

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 細胞シート工学2014

    • Author(s)
      小林慎一朗, 岡野光夫, 江口晋
    • Journal Title

      消化器外科

      Volume: 37 Pages: 1321-1332

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Construction of Liver Tissue in vivo with Preparative Partial Hepatic Irradiation and Growth Stimulus: Investigations of Less Invasive Techniques and Progenitor Cells2013

    • Author(s)
      Kensuke Miyazaki, Kosho Yamanouchi, Yusuke Sakai, Izumi Yamaguchi, Mitsuhisa Takatsuki, Tamotsu Kuroki, Chandan Guha, and Susumu Eguchi
    • Journal Title

      Journal of Surgical Research

      Volume: 185 (2) Issue: 2 Pages: 889-895

    • DOI

      10.1016/j.jss.2013.06.016

    • NAID

      120006986772

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Rapid fabricating technique for multi-layered human hepatic cell sheets by forceful contraction of the fibroblast monolayer2013

    • Author(s)
      Yusuke Sakai, Makiko Koike, Hideko Hasegawa, Kosho Yamanouchi, Akihiko Soyama, Mitsuhisa Takatsuki, Tamotsu Kuroki, Kazuo Ohashi, Teruo Okano, and Susumu Eguchi
    • Journal Title

      PLoS One

      Volume: 8 (7) Issue: 7 Pages: e70970-e70970

    • DOI

      10.1371/journal.pone.0070970

    • NAID

      120006986139

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Transplanted Fibroblast Cell Sheets Promote Migration of Hepatic Progenitor Cells in the Incised Host Liver in Allogeneic Rat Model2012

    • Author(s)
      Izumi Muraoka, et al.
    • Journal Title

      Journal of Tissue Engineering and Regenerative Medicine

      Volume: 172 Issue: 2 Pages: 206-206

    • DOI

      10.1016/j.jss.2011.11.283

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Recurrence-free survival more than 10 years after liver resection for hepatocellular carcinoma.2011

    • Author(s)
      Eguchi S, Kanematsu T, Arii S, Omata M, Kudo M, Sakamoto M, Takayasu K, Makuuchi M, Matsuyama Y, Monden M .
    • Journal Title

      Br J Surg

      Volume: 98(4) Issue: 4 Pages: 552-557

    • DOI

      10.1002/bjs.7393

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Elective living donor liver transplantation by hybrid hand-assisted laparoscopic surgery and short upper midline laparotomy.2011

    • Author(s)
      Eguchi S, Takatsuki M, Soyama A, Hidaka M, Tomonaga T, Muraoka I, Kanematsu T.
    • Journal Title

      Surgery

      Volume: 150 Issue: 5 Pages: 1002-1005

    • DOI

      10.1016/j.surg.2011.06.021

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Liver transplantation for patients with human immunodeficiency virus and hepatitis C virus coinfection with special reference to hemophiliac recipients in Japan.2011

    • Author(s)
      Eguchi S, Soyama A, Hidaka M, Takatsuki M, Muraoka I, Tomonaga T, Kanematsu T.
    • Journal Title

      Surg Today

      Volume: 41(10) Issue: 10 Pages: 1325-31

    • DOI

      10.1007/s00595-010-4556-x

    • NAID

      10030228509

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lack of grafted liver rejuvenation in adult-to-pediatric liver transplantation.2011

    • Author(s)
      Eguchi S, Takatsuki M, Hidaka M, Soyama A, Muraoka I, Tomonaga T, Shimokawa I, Kanematsu T.
    • Journal Title

      Dig Dis Sci

      Volume: 56(8) Issue: 5 Pages: 1542-7

    • DOI

      10.1007/s10620-010-1445-5

    • NAID

      120006984915

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Perioperative symbiotic treatment to prevent infectious.2011

    • Author(s)
      Eguchi S, Takatsuki M, Hidaka M, Soyama A, Ichikawa T, Kanematsu T.
    • Journal Title

      Am J surg

      Volume: 201 Issue: 4 Pages: 498-502

    • DOI

      10.1016/j.amjsurg.2010.02.013

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Honoring the contract with our patients: outcome after repeated re-transplantation of the liver.2011

    • Author(s)
      Eguchi S, Soyama A, Mergental H, van den Berg AP, Scheenstra R, Porte RJ, Slooff MJH.
    • Journal Title

      Clin Transplant

      Volume: 25 Issue: 2

    • DOI

      10.1111/j.1399-0012.2010.01389.x

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Living donor liver transplantation2011

    • Author(s)
      Soyama A, Eguchi S, Yanaga K, Takatsuki M, Hidaka M, Kanematsu T
    • Journal Title

      Surg Today

      Volume: 41 Issue: 7 Pages: 1026-1028

    • DOI

      10.1007/s00595-010-4376-z

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Technical refinements of bile duct division in living donor liver surgery.2011

    • Author(s)
      Takatsuki M, Eguchi S, Yamanouchi K, Hidaka M, Soyama A, Kanematsu T.
    • Journal Title

      J Hepatobiliary Pancreat Sci

      Volume: 18 Issue: 2 Pages: 170-5

    • DOI

      10.1007/s00534-010-0322-0

    • NAID

      10029286157

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Use ofstepwise versus straightforward clamping of biliary drainage tubes after iving-donor liver transplantation: a prospective, randomized trial.2011

    • Author(s)
      Eguchi S, Takatsuki M, Soyama A, Hidaka M, Muraoka I, Kanematsu T.
    • Journal Title

      J Hepatobiliary Pancreat Sci

      Volume: Epub ahead of print Issue: 4 Pages: 379-381

    • DOI

      10.1007/s00534-011-0424-3

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Is Preservation of Middle Hepatic Vein Tributaries during Right Hemi-Hepatectomy Beneficial for Live Donor Liver Transplantation?2011

    • Author(s)
      Eguchi S, Takatsuki M, Soyama A, Hidaka M, Muraoka I, Kanematsu T
    • Journal Title

      Hepatogastroenterology

      Volume: 59 Pages: 115-116

    • NAID

      120006985475

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 細胞シート工学を利用した血管誘導ヒト肝組織の迅速な自己構築2015

    • Author(s)
      堺裕輔、小池真章子、長谷川英子、山之内孝彰、曽山明彦、日高匡章、高槻光寿、黒木保、江口晋
    • Organizer
      第115回日本外科学会定期学術集会
    • Place of Presentation
      名古屋国際会議場(名古屋)
    • Year and Date
      2015-04-16 – 2015-04-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] Rapid fabrication of engineered liver tissue using novel fibroblast system2014

    • Author(s)
      Yusuke Sakai, Makiko Koike, Hideko Hasegawa, Kosho Yamanouchi, Akihiko Soyama, Masaaki Hidaka, Mitsuhisa Takatsuki, Tamotsu Kuroki, Teruo Okano, and Susumu Eguchi
    • Organizer
      9th World Congress on Alternatives and Animal Use in the Life Sciences (WC9)
    • Place of Presentation
      Prague, Czech Republic
    • Year and Date
      2014-08-24 – 2014-08-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] Reconstruction of Vascularized Subcutaneous Liver Tissue for Minimally Invasive Cell Therapy2014

    • Author(s)
      Yusuke Sakai, Makiko Koike, Kosho Yamanouchi, Akihiko Soyama, Masaaki Hidaka, Mitsuhisa Takatsuki, Tamotsu Kuroki, and Susumu Eguchi
    • Organizer
      ASGCT 18th Annual Meeting
    • Place of Presentation
      New Orleans, LA, USA
    • Year and Date
      2014-05-13 – 2014-05-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] Reversibly-assembled microfluidic device consists of microwells and microchannels for stable perfusion culture of spheroid array2012

    • Author(s)
      Yusuke Sakai, Koji Hattori, Shinji Sugiura, Toshiyuki Kanamori, and Kohji Nakazawa
    • Organizer
      2012 IEEE EMBS Micro and Nanotechnology in Medicine Conference, Hawaii, USA
    • Place of Presentation
      アメリカ
    • Related Report
      2012 Research-status Report
  • [Presentation] Elective living donor liver transplantation with splenectomy by hybrid hand-assisted laparoscopic surgery and small upper midline laparotomy.2011

    • Author(s)
      Eguchi S, Takatsuki M, Soyama A, Hidaka M, Muraoka I, Kanematsu T.
    • Organizer
      97th Annual College of Surgeons Clinical Congress
    • Place of Presentation
      SF, USA
    • Related Report
      2011 Research-status Report
  • [Presentation] The outcome of ABO-incompatible living donor liver transplantation : A single center experience in Japan.2011

    • Author(s)
      Takatsuki M, Eguchi S, Hidaka M, Soyama A, Muraoka I, Kuroki T, Adachi T, Kanetaka K, Kanematsu T.
    • Organizer
      97th Annual College of Surgeons Clinical Congress
    • Place of Presentation
      SF, USA
    • Related Report
      2011 Research-status Report
  • [Presentation] Standardized less invasive living donor hemihepatectomy by the hybrid method through short upper midline incision.2011

    • Author(s)
      Soyama A, Takatsuki M, Muraoka I,Ohno S, Adachi T, Kuroki T, Eguchi S.
    • Organizer
      12th CAST
    • Place of Presentation
      Seoul, Korea
    • Related Report
      2011 Research-status Report
  • [Presentation] Long-term outcome of endoscopic stent placement for bilary stricture after living donor liver transplantation.2011

    • Author(s)
      Takatsuki M,Soyama A, Hidaka M, Muraoka I, Kuroki T, Ichikawa T, Nakao K, Eguchi S
    • Organizer
      12th CAST
    • Place of Presentation
      Seoul, Korea
    • Related Report
      2011 Research-status Report
  • [Presentation] Impact of peripheral blood CD4+ adenosine triphosphate activity in long-term living donor liver transplantation under weaning of immunosuppresion.2011

    • Author(s)
      Takatsuki M,, Eguchi S, Hidaka M, Soyama A, Tomonaga T, Muraoka I, Kanematsu T.
    • Organizer
      17th ILTS
    • Place of Presentation
      Valencia, Spain
    • Related Report
      2011 Research-status Report
  • [Presentation] Elective living donor liver transplantation by hybrid hand-assisted laparoscopic surgery and short upper midline laparotomy.2011

    • Author(s)
      Eguchi S, Takatsuki M, Soyama A, Hara T, Muraoka I.
    • Organizer
      12th CAST
    • Place of Presentation
      Seoul, Korea
    • Related Report
      2011 Research-status Report
  • [Presentation] Expression of E-cadherin in hepatocellular carcinoma with previously local therapies in the explanted cirrhotic liver for liver transplantation.2011

    • Author(s)
      Hidaka M, Takatsuki M, Soyama A, Okudaira S, Muraoka I, Adachi T, Kuroki T, Kanematsu T, Eguchi S.
    • Organizer
      5th ILCA
    • Place of Presentation
      Hong Kong, China
    • Related Report
      2011 Research-status Report
  • [Presentation] Induction of hepatic progenitor cells by transplanted rat dermal fibroblast allograft sheet on an incised rat liver.2011

    • Author(s)
      Muraoka I, Soyama A, Takatsuki M, Tomonaga T, Hidaka M, Kanematsu T,Hishikawa Y, Koji T, Utoh R, Ohashi K, Eguchi S.
    • Organizer
      62nd AASLD
    • Place of Presentation
      SF, USA
    • Related Report
      2011 Research-status Report
  • [Presentation] 腹腔鏡補助での新しい取り組み:上腹部正中切開でのハイブリッド生体肝移植ドナー&レシピエント手術2011

    • Author(s)
      江口 晋、高槻光寿、日高匡章、曽山明彦、村岡いづみ、足立智彦、黒木 保、兼松隆之
    • Organizer
      第23回 日本肝胆膵外科学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2011 Research-status Report
  • [Presentation] ハイブリッド手技を用いた生体ドナー、レシピエント肝移植手術2011

    • Author(s)
      江口 晋、高槻光寿、曽山明彦、日高匡章、木下綾華、原 貴信、村岡いづみ、足立智彦、黒木 保、兼松隆之
    • Organizer
      第47回 日本移植学会総会
    • Place of Presentation
      仙台
    • Related Report
      2011 Research-status Report
  • [Presentation] 異所性肝組織構築のための再生医療デバイスの創成

    • Author(s)
      堺裕輔、小池真章子、山之内孝彰、曽山明彦、高槻光寿、黒木保、鵜頭理恵、大橋一夫、岡野光夫、江口晋
    • Organizer
      第68回日本消化器外科学会総会
    • Place of Presentation
      宮崎(シーガイアコンベンションセンター)
    • Related Report
      2013 Research-status Report
  • [Presentation] ヒト初代肝細胞/線維芽細胞複合シートが創造する第二の肝臓

    • Author(s)
      堺裕輔、高槻光寿、江口晋
    • Organizer
      JDDW2013
    • Place of Presentation
      東京(グランドプリンスホテル新高輪)
    • Related Report
      2013 Research-status Report
  • [Presentation] 肝移植の代替または再生補助療法としてのヒト肝細胞シートを用いた再生医療デバイスの開発

    • Author(s)
      高槻光寿、堺裕輔、江口晋
    • Organizer
      第40回日本肝臓学会西部会
    • Place of Presentation
      岐阜(長良川国際会議場)
    • Related Report
      2013 Research-status Report
  • [Presentation] ヒト初代肝細胞複合シート移植における支持細胞の種類の効果

    • Author(s)
      堺裕輔、小池真章子、長谷川英子、山之内孝彰、日高匡章、曽山明彦、高槻光寿、黒木保、岡野光夫、江口晋
    • Organizer
      第13回日本再生医療学会総会
    • Place of Presentation
      京都(国立京都国際会館)
    • Related Report
      2013 Research-status Report
  • [Presentation] 肝細胞/各種支持細胞共培養シートの構造と機能発現の評価

    • Author(s)
      小池真章子、堺裕輔、黒木保、江口晋
    • Organizer
      第13回日本再生医療学会総会
    • Place of Presentation
      京都(国立京都国際会館)
    • Related Report
      2013 Research-status Report
  • [Presentation] ヒト肝細胞シートによる肝再生を目指して ~ヒト肝細胞シート作製技術の確立~

    • Author(s)
      堺裕輔、高槻光寿、山之内孝彰、曽山明彦、村岡いづみ、大橋一夫、江口晋
    • Organizer
      第48回日本肝臓学会総会
    • Place of Presentation
      石川
    • Related Report
      2012 Research-status Report
  • [Presentation] 共培養技術に基づく重層化肝細胞シートの開発

    • Author(s)
      堺裕輔、高槻光寿、山之内孝彰、曽山明彦、村岡いづみ、田中貴之、山口泉、木下綾華、原貴信、鵜頭理恵、大橋一夫、岡野光夫、黒木保、江口晋
    • Organizer
      第11回日本再生医療学会総会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] 線維芽細胞/肝細胞重層化シートの開発およびin vivo肝特異機能発現

    • Author(s)
      堺裕輔、高槻光寿、山之内孝彰、曽山明彦、鵜頭理恵、大橋一夫、岡野光夫、黒木保、江口晋
    • Organizer
      第19回肝細胞研究会
    • Place of Presentation
      北海道
    • Related Report
      2012 Research-status Report
  • [Presentation] Development of a multilayered fibroblast/hepatocyte sheet for regenerative medicine

    • Author(s)
      Yusuke Sakai, Mitsuhisa Takatsuki, Kosho Yamanouchi, Akihiko Soyama, Izumi Muraoka, Rie Utoh, Kazuo Ohashi, Teruo Okano, Tamotsu Kuroki, and Susumu Eguchi
    • Organizer
      3rd TERMIS World Congress in Vienna
    • Place of Presentation
      オーストリア
    • Related Report
      2012 Research-status Report
  • [Presentation] 再生医療のための肝細胞組織工学

    • Author(s)
      堺裕輔、小池真章子、山之内孝彰、曽山明彦、高槻光寿、黒木保、江口晋
    • Organizer
      第27回長崎DDS・再生医療研究会
    • Place of Presentation
      長崎
    • Related Report
      2012 Research-status Report
  • [Presentation] ヒト初代肝細胞/線維芽細胞複合シートによる異所性肝組織構築

    • Author(s)
      堺裕輔、小池真章子、長谷川英子、山之内孝彰、曽山明彦、高槻光寿、黒木保、鵜頭理恵、大橋一夫、岡野光夫、江口晋
    • Organizer
      第12回日本再生医療学会総会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] 共培養型肝細胞シートにおける支持細胞の効果

    • Author(s)
      小池真章子、堺裕輔、高槻光寿、曽山明彦、虎島泰洋、藤田文彦、金高賢悟、黒木保、江口晋
    • Organizer
      第12回日本再生医療学会総会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Book] 再生医療用語ハンドブック: 7 消化器②2015

    • Author(s)
      江口晋 共著
    • Total Pages
      5
    • Publisher
      株式会社メディカルトリビューン
    • Related Report
      2014 Annual Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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