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Creation of iPS-derived Hepatocyte-based Therapeutic Modality Using Liver Micro-organoids

Research Project

Project/Area Number 26670587
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field General surgery
Research InstitutionOsaka University

Principal Investigator

OHASHI KAZUO  大阪大学, 薬学研究科(研究院), 教授 (40364062)

Co-Investigator(Renkei-kenkyūsha) MIZUGUCHI Hiroyuki  大阪大学, 薬学研究科, 教授 (50311387)
YAMADA Masumi  千葉大学, 工学研究科, 准教授 (30546784)
Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords人工臓器学 / 細胞療法 / 組織工学 / 再生医療 / 肝細胞 / iPS細胞 / 薬物代謝
Outline of Final Research Achievements

The aim of this project was to create several fundamental technologies that allow us to create cell-loaded transplantable devices that could be used for cell-based therapies toward liver diseases. The fundamental concept is that cells will be localized after transplantation, instead of scattering the cells after conventional cell infusion-based transplantation procedures.
Hepatocytes are loaded into ultra-thin (<200micrometer in diameter) alginate micro-fibers using micro-fluidic devices and microfluidic technologies for creating liver micro-organoids. We have confirmed liver functions at considerable levels of the liver micro-organoids made of HepG2 cells or iPS-derived hepatocytes with non-parenchymal cells. We have also confirmed that the liver micro-organoids were durable for transplantation procedures on a mouse transplantation experiments.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (22 results)

All 2016 2015 2014

All Journal Article (9 results) (of which Peer Reviewed: 8 results,  Open Access: 4 results,  Acknowledgement Compliant: 6 results) Presentation (11 results) (of which Int'l Joint Research: 3 results,  Invited: 5 results) Book (2 results)

  • [Journal Article] Transplantation of a human iPSC-derived hepatocyte sheet increases survival in mice with acute liver failure.2016

    • Author(s)
      Nagamoto Y., Takayama K., Ohashi K., Okamoto R., Sakurai F., Tachibana M., Kawabata K., Mizuguchi H.
    • Journal Title

      Jpurnal of Hepatology

      Volume: 64 Issue: 5 Pages: 1068-1075

    • DOI

      10.1016/j.jhep.2016.01.004

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] アルコール性高ホモシステイン血症に対する核内受容体SHP欠損による抑制作用2016

    • Author(s)
      土谷博之、大橋一夫
    • Journal Title

      日本アルコール・薬物医学会雑誌

      Volume: in press

    • NAID

      40021022500

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Efficient gene transduction of dispersed islet cells in culture using fiber-modified adenoviral vectors.2015

    • Author(s)
      Hanayama H, Ohashi K, Utoh R, Shimizu H, Ise K, Sakurai F, MIzuguchi H, Tsuchiya H, Okano T, Gotoh M.
    • Journal Title

      Cell Medicine

      Volume: 8 Issue: 1-2 Pages: 31-38

    • DOI

      10.3727/215517915x689083

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Human laminin isotype coating for creating islet cell sheets.2015

    • Author(s)
      Yahashita S, Ohashi K, Utoh R, Okano T, Yamamoto M.
    • Journal Title

      Cell Medicine

      Volume: 8 Issue: 1-2 Pages: 39-46

    • DOI

      10.3727/215517915x689029

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Vascularized subcutaneous human liver tissue from engineered hepatocyte/fibroblast sheets in mice2015

    • Author(s)
      Yusuke Sakai, Kosho Yamanouchi, Kazuo Ohashi, Makiko Koike, Rie Utoh, Hideko Hasegawa, Izumi Muraoka, Takashi Suematsu, Akihiko Soyama, Masaaki Hidaka, Mitsuhisa Takatsuki, Tamotsu Kuroki, Susumu Eguchi
    • Journal Title

      Biomaterials

      Volume: 65 Pages: 66-75

    • DOI

      10.1016/j.biomaterials.2015.06.046

    • NAID

      120006986875

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Evaluation of transduction properties of an adenovirus vector in neonatal mice.2015

    • Author(s)
      Iizuka S, Sakurai F, Shimizu K, Ohashi K, Nakamura S-I, Tachibana M, Mizuguchi H.
    • Journal Title

      BioMed Research International

      Volume: 685374 Pages: 1-10

    • DOI

      10.1155/2015/685374

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adenovirus-mediated Bcl-Xl gene therapy combined with pronase treatment protects the small intestine from radiation-induced enteritis in mouse model.2015

    • Author(s)
      Koyama F, Uchimoto K, Fujii H, Hamada H, Ohashi K, Nomi T, Nakagawa T, Nakamura S, Ueda T, Nakajima Y
    • Journal Title

      J Genet Synd Gene Ther

      Volume: 5 Issue: 05

    • DOI

      10.4172/2157-7412.1000239

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Efficient Gene Transduction to Dispersed Islet Cells in Culture Using Fiber-modified Adenoviral Vectors2015

    • Author(s)
      Hanayama H, Ohashi K, Utoh R, Shimizu H, Ise K, Sakurai F, Mizuguchi H, Tsuchiya H, Okano T, Gotoh M.
    • Journal Title

      Cell Medicine

      Volume: in press

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] CCAAT/enhancer binding protein-mediated regulat ion of TGF β receptor 2 expression determine the hepatoblast fate decision2014

    • Author(s)
      Takayama K., Kawabata K., Nagamoto Y., Inamura M., Ohashi K., Okuno H., Yamaguchi T., Tashiro K., Sakurai F., Hayakawa T., Okano T., Furue MK., Mizuguchi H.
    • Journal Title

      Development

      Volume: 141 Issue: 1 Pages: 91-100

    • DOI

      10.1242/dev.103168

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] Hepatocyte, a cell source for liver repopulation and organogenesis2015

    • Author(s)
      Kazuo Ohashi
    • Organizer
      Cell Transplantation Society 2015 Meeting
    • Place of Presentation
      メルボルン
    • Year and Date
      2015-11-15 – 2015-11-19
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Hepatocyte Transplantation for the Assessment of Hepatocyte Proliferation and Their Streaming2015

    • Author(s)
      Ohashi K, Yamashita S, Utoh R, Tsuchiya H, Yamamoto M
    • Organizer
      2015 IPITA-CTS-IXA Joint Meeting
    • Place of Presentation
      Melbourne Convention Center
    • Year and Date
      2015-11-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Therapeutic Effects of Ectopic Liver Tissue Engineering on Lethal Acute Liver Failure in Mice2015

    • Author(s)
      Ohashi K, Kuge H, Kosai K-I, Tsuchiya H
    • Organizer
      2015 IPITA-CTS-IXA Joint Meeting
    • Place of Presentation
      Melbourne Convention Center
    • Year and Date
      2015-11-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Hepatocyte: A Cell Source for Liver Regeneration and Liver Organogenesis2015

    • Author(s)
      Ohashi K
    • Organizer
      2015 IPITA-CTS-IXA Joint Meeting
    • Place of Presentation
      Melbourne Convention Center
    • Year and Date
      2015-11-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 肝臓における核内受容体SHPの新たな生理機能の解明2015

    • Author(s)
      土谷博之、大橋一夫、Li Wang
    • Organizer
      第11回広島肝臓プロジェクト研究センターシンポジウム
    • Place of Presentation
      広島
    • Year and Date
      2015-07-04
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 次世代治療としての生体内肝組織構築(肝組織工学)開発の現状と展望2015

    • Author(s)
      大橋一夫
    • Organizer
      第22回肝細胞研究会
    • Place of Presentation
      米子コンベンションセンター
    • Year and Date
      2015-06-04 – 2015-06-05
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 次世代治療としての生体内肝組織構築(肝組織工学)開発の現状と展望2015

    • Author(s)
      大橋一夫
    • Organizer
      第22回肝細胞研究会 レビュー
    • Place of Presentation
      米子
    • Year and Date
      2015-06-04
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 転写因子によるホモシステイン代謝制御機構の解明2015

    • Author(s)
      土谷博之、大橋一夫、Li Wang
    • Organizer
      第22回肝細胞研究会
    • Place of Presentation
      米子
    • Year and Date
      2015-06-04
    • Related Report
      2015 Annual Research Report
  • [Presentation] 第51回肝細胞単層組織からの臓器創生―臓器創生幹細胞としての肝細胞の働き2015

    • Author(s)
      大橋一夫
    • Organizer
      日本肝臓学会
    • Place of Presentation
      熊本日航ホテル
    • Year and Date
      2015-05-21 – 2015-05-22
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 膵島組織工学を目指した単離膵島細胞への ファイバー改変アデノウイルスベクターによる 遺伝子導入2014

    • Author(s)
      花山寛之、大橋一夫、鵜頭理恵、伊勢一哉、櫻井文教、水口裕之、岡野光夫、後藤満一
    • Organizer
      第41回日本臓器保存生物医学会総会
    • Place of Presentation
      千里ライフサイエンスセンター
    • Year and Date
      2014-11-28 – 2014-11-29
    • Related Report
      2014 Research-status Report
  • [Presentation] ラミニンを介した単離膵島細胞の単層組織化2014

    • Author(s)
      山下信吾、鵜頭理恵、Tatsuya Kin、A M James Shapiro、後藤満一、岡野光夫、大橋一夫
    • Organizer
      第41回日本臓器保存生物医学会総会
    • Place of Presentation
      千里ライフサイエンスセンター
    • Year and Date
      2014-11-28 – 2014-11-29
    • Related Report
      2014 Research-status Report
  • [Book] 医学大辞典 肝細胞移植・人工肝臓2015

    • Author(s)
      大橋一夫
    • Total Pages
      3100
    • Publisher
      南山堂
    • Related Report
      2015 Annual Research Report
  • [Book] 医学大事典第20版2015

    • Author(s)
      大橋一夫
    • Total Pages
      3101
    • Publisher
      南山堂
    • Related Report
      2014 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2017-05-10  

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