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Fabrication of human liver with mimicking hepatic lobule structures by alternately-arranged human hepatocyte/endotherial cell tissue transplantation

Research Project

Project/Area Number 16H05908
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionNagasaki University

Principal Investigator

SAKAI Yusuke  長崎大学, 医歯薬学総合研究科(医学系), 助教 (10608904)

Research Collaborator EGUCHI Susumu  
NAKAZAWA Kohji  
KOIKE Makiko  
YAMANOUCHI Kosho  
SOYAMA Akihiko  
HIDAKA Masaaki  
TAKATSUKI Mitsuhisa  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥25,480,000 (Direct Cost: ¥19,600,000、Indirect Cost: ¥5,880,000)
Fiscal Year 2018: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2017: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2016: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000)
Keywords肝細胞 / 内皮細胞 / 肝臓 / アレイ化 / 再生医療 / 管腔 / 細胞シート / 血管新生
Outline of Final Research Achievements

Alternately-arranged human hepatocyte/ endothelial cell tissue (AHET) could contribute to oxygen supply, survival, three-dimensional organization, and maintenance of liver-specific functions. In this study, we aimed to fabricate AHET by using micropatterning technology and cell sheet engineering.
Multi-pored silicone film (MPSF) were prepared using microchannels. Human primary hepatocytes adhered to the perforated region of MPSF. The hepatocytes densely aggregated and were patterned. The hepatocytes were cocultured with HUVEC, and alternately-arranged human hepatocyte/ endothelial cell was generated. hADSC supported the formation of the luminal-like structure of HUVEC. AHET could be harvested and was an implantable tissue.

Academic Significance and Societal Importance of the Research Achievements

これまでに、規則的な血管網を持つ細胞だけで構成された移植用組織体の作製は困難であった。本研究では、肝小葉構造に基づき規則的に内皮細胞を配置すると共に、細胞のみで管腔構造を形成させる技術を確立した。ヒト初代肝細胞-内皮細胞索状組織(AHET)は、移植用の組織体として新しい移植医療に応用し得る可能性を秘めている。さらに、本技術を基盤として、他の機能性細胞(膵島細胞等)への迅速な応用が考え得る。これらのことから、次世代の移植再生医療技術として波及効果は多大である。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (29 results)

All 2019 2018 2017 2016

All Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 2 results) Presentation (16 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] An engineered cell sheet composed of human islets and human fibroblast, bone marrow?derived mesenchymal stem cells, or adipose?derived mesenchymal stem cells: An in vitro comparison study2018

    • Author(s)
      Imamura Hajime、Adachi Tomohiko、Kin Tatsuya、Ono Shinichiro、Sakai Yusuke、Adachi Toshiyuki、Soyama Akihiko、Hidaka Masaaki、Takatsuki Mitsuhisa、Shapiro A.M. James、Eguchi Susumu
    • Journal Title

      Islets

      Volume: 10 Issue: 3 Pages: e1445948-e1445948

    • DOI

      10.1080/19382014.2018.1445948

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Time‐dependent structural and functional characterization of subcutaneous human liver tissue2018

    • Author(s)
      Sakai Yusuke、Koike Makiko、Yamanouchi Kosho、Soyama Akihiko、Hidaka Masaaki、Kuroki Tamotsu、Eguchi Susumu
    • Journal Title

      Journal of Tissue Engineering and Regenerative Medicine

      Volume: 12 Issue: 12 Pages: 2287-2298

    • DOI

      10.1002/term.2761

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Spontaneous hepatocyte migration towards an endothelial cell tube network2018

    • Author(s)
      Baimakhanov Zhassulan、Sakai Yusuke、Yamanouchi Kosho、Hidaka Masaaki、Soyama Akihiko、Takatsuki Mitsuhisa、Eguchi Susumu
    • Journal Title

      Journal of Tissue Engineering and Regenerative Medicine

      Volume: 12 Issue: 3

    • DOI

      10.1002/term.2577

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Controlled cell morphology and liver-specific function of engineered primary hepatocytes by fibroblast layer cell densities2018

    • Author(s)
      Sakai Yusuke、Koike Makiko、Kawahara Daisuke、Hasegawa Hideko、Murai Tomomi、Yamanouchi Kosho、Soyama Akihiko、Hidaka Masaaki、Takatsuki Mitsuhisa、Fujita Fumihiko、Kuroki Tamotsu、Eguchi Susumu
    • Journal Title

      Journal of Bioscience and Bioengineering

      Volume: 印刷中 Issue: 2 Pages: 249-257

    • DOI

      10.1016/j.jbiosc.2018.02.006

    • NAID

      40021645454

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tissue Repair Promotion and Functional Tissue Fabrication of Digestive Organ by Cell Sheets2018

    • Author(s)
      堺 裕輔、江口 晋
    • Journal Title

      MEMBRANE

      Volume: 43 Issue: 2 Pages: 34-39

    • DOI

      10.5360/membrane.43.34

    • NAID

      130006638816

    • ISSN
      0385-1036, 1884-6440
    • Related Report
      2017 Annual Research Report
  • [Journal Article] In vivo construction of liver tissue by implantation of a hepatic non-parenchymal/adipose-derived stem cell sheet2017

    • Author(s)
      Mio Fujii, Kosho Yamanouchi, Yusuke Sakai, Zhassulan Baimakhanov, Izumi Yamaguchi, Akihiko Soyama, Masaaki Hidaka, Mitsuhisa Takatsuki, Tamotsu Kuroki, Susumu Eguchi
    • Journal Title

      Journal of Tissue Engineering and Regenerative Medicine

      Volume: 印刷中 Issue: 1 Pages: e287-e295

    • DOI

      10.1002/term.2424

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 細胞を用いた肝再生医療の最前線2017

    • Author(s)
      岡田 尚子、堺 裕輔、江口 晋
    • Journal Title

      PHARMSTAGE

      Volume: 17 Pages: 10-16

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Toyocamycin attenuates free fatty acid-induced hepatic steatosis and apoptosis in cultured hepatocytes and ameliorates nonalcoholic fatty liver disease in mice2017

    • Author(s)
      Ikuko Takahara, Yuko Akazawa, Maiko Tabuchi, Katsuya Matsuda, Hisamitsu Miyaaki, Youko Kido, Yasuko Kanda, Naota Taura, Ken Ohnita, Fuminao Takeshima, Yusuke Sakai, Susumu Egushi, Masahiro Nakashima, Kazuhiko Nakao
    • Journal Title

      PLoS One

      Volume: 12 Issue: 3 Pages: e0170591-e0170591

    • DOI

      10.1371/journal.pone.0170591

    • NAID

      120006987538

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Equal distribution of MSCs after hepatic ischemia reperfusion injury2016

    • Author(s)
      Askhat Isbambetov, Zhassulan Baimakhanov, Akihiko Soyama, Masaaki Hidaka, Yusuke Sakai, Mitsuhisa Takatsuki, Tamotsu Kuroki, Susumu Eguchi
    • Journal Title

      Journal of Surgical Research

      Volume: 203 Issue: 2 Pages: 360-367

    • DOI

      10.1016/j.jss.2016.03.057

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Up-regulated extracellular matrix components and inflammatory chemokines may impair the regeneration of cholestatic liver2016

    • Author(s)
      Shuai Zhang, Tao-Sheng Li, Akihiko Soyama, Takayuki Tanaka, Chen Yan, Yusuke Sakai, Masaaki Hidaka, Ayaka Kinoshita, Koji Natsuda, Mio Fujii, Tota Kugiyama, Zhassulan Baimakhanov, Tamotsu Kuroki, Weili Gu, Susumu Eguchi
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 26540-26540

    • DOI

      10.1038/srep26540

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 血管誘導を伴う皮下性ヒト肝組織構築2019

    • Author(s)
      堺裕輔、日髙匡章、高槻光寿、江口晋
    • Organizer
      第38回長崎障害者支援再生医療研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 管腔構造を有するヒト肝細胞/内皮細胞索状組織作製技術の確立2019

    • Author(s)
      堺裕輔、中澤浩二、日高匡章、高槻光寿、江口晋
    • Organizer
      第16回日本再生医療学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Spontaneous formation of three-dimensional cell cysts from chemically-induced liver progenitors2019

    • Author(s)
      Yu Huang, Yusuke Sakai, Takanobu Hara, Takeshi Katsuda, Takahiro Ochiya, Susumu Eguchi
    • Organizer
      第16回日本再生医療学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 血管誘導を伴う皮下性ヒト肝組織構築での遺伝子発現解析2019

    • Author(s)
      堺裕輔、高槻光寿、江口晋
    • Organizer
      第119回日本外科学会定期学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 抗原性を消失させた肝細胞/肝癌細胞シート作製の試み2019

    • Author(s)
      岡田怜美、高槻光寿、堺裕輔、日髙匡章、足立智彦、大野慎一郎、夏田孔史、濵田隆志、前川恭一郎、池田裕明、江口晋
    • Organizer
      第119回日本外科学会定期学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 胆汁うっ滞肝モデルにおける肝切除後の肝内リンパ管新生の影響2019

    • Author(s)
      濵田隆史、日髙匡章、堺裕輔、夏田孔史、足立智彦、大野慎一郎、前川恭一郎、三好敬之、黄宇、飛永修一、田渕聡、高槻光寿、江口晋
    • Organizer
      第119回日本外科学会定期学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒト肝分離における患者背景の検討2019

    • Author(s)
      三好敬之、堺裕輔、濵田隆史、前川恭一郎、夏田孔史、大野慎一郎、足立智彦、日髙匡章、高槻光寿、江口晋
    • Organizer
      第119回日本外科学会定期学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Time-dependent liver-specific gene expressions of vascularized subcutaneous human liver tissue2018

    • Author(s)
      Yusuke Sakai, Akihiko Soyama, Masaaki Hidaka, Mitsuhisa Takatsuki, Susumu Eguchi
    • Organizer
      5th TERMIS World Congress
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Rapid fabrication of engineered human primary hepatocyte/fibroblast sheets for prevention of postoperative hepatic insufficiency2018

    • Author(s)
      Yu Huang, Yusuke Sakai, Akihiko Soyama, Masaaki Hidaka, Mitsuhisa Takatsuki, Susumu Eguchi
    • Organizer
      5th TERMIS World Congress
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 効率的・移植可能な肝胆膵領域での再生医療2018

    • Author(s)
      江口晋、黄宇、堺裕輔
    • Organizer
      第17回日本再生医療学会総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Unique cell morphologies and liver-specific gene expressions of chemically-induced liver progenitors2018

    • Author(s)
      Yu Huang、Yusuke Sakai、Takanobu Hara、Takeshi Katsuda、Takahiro Ochiya、Susumu Eguchi
    • Organizer
      第17回日本再生医療学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 術後急性肝不全予防のための迅速な肝細胞複合シート作製2017

    • Author(s)
      堺裕輔、小池真章子、曽山明彦、日高匡章、高槻光寿、江口晋
    • Organizer
      第16回日本再生医療学会総会
    • Place of Presentation
      仙台国際センター(宮城県、仙台市)
    • Year and Date
      2017-03-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] 細胞シート工学を利用した血管網を有する皮下培養型ヒト肝組織作製2017

    • Author(s)
      堺裕輔、高槻光寿、江口晋
    • Organizer
      第103回日本消化器病学会総会
    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
  • [Presentation] 孔貫通型シリコーンフィルムを利用した肝類似パターニング2017

    • Author(s)
      久賀千尋、堺裕輔、中澤浩二、江口晋
    • Organizer
      第54回化学関連支部合同九州大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 肝特異的な特徴を有するヒト肝組織の皮下構築と機能発現解析2016

    • 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、江口晋
    • Organizer
      第23回肝細胞研究会
    • Place of Presentation
      大阪大学中之島センター(大阪府、大阪市)
    • Year and Date
      2016-07-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] 安定した肝細胞複合シート作製のための線維芽細胞培養条件の検討2016

    • Author(s)
      小池真章子、堺裕輔、川原大輔、高槻光寿、江口晋
    • Organizer
      第23回肝細胞研究会
    • Place of Presentation
      大阪大学中之島センター(大阪府、大阪市)
    • Year and Date
      2016-07-07
    • Related Report
      2016 Annual Research Report
  • [Patent(Industrial Property Rights)] 培養組織及びその製造方法2019

    • Inventor(s)
      堺裕輔、江口晋、足立智彦、黄宇
    • Industrial Property Rights Holder
      堺裕輔、江口晋、足立智彦、黄宇
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] 肝前駆細胞を含む細胞集団を製造する方法2019

    • Inventor(s)
      堺裕輔、江口晋
    • Industrial Property Rights Holder
      堺裕輔、江口晋
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] シート状物貼付デバイス2018

    • Inventor(s)
      堺裕輔、江口晋、丸屋安広、大橋文哉、鮫島正
    • Industrial Property Rights Holder
      堺裕輔、江口晋、丸屋安広、大橋文哉、鮫島正
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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