Integrated in vit-roin vivo organization of liver tissues having a functional bile duct network

• Project/Area Number: 22650108
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Biomedical engineering/Biological material science
• Research Institution: The University of Tokyo
• Principal Investigator: SAKAI Yasuyuki 東京大学, 生産技術研究所, 教授 (00235128)
• Co-Investigator(Kenkyū-buntansha): OCHIYA Takahiro 国立がん研究センター, 研究所, 分子細胞治療研究分野長 (60192530)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,440,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥540,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,100,000 (Direct Cost: ¥1,100,000)
• Keywords: 細胞・組織工学 / マクロ組織極性 / 移植・再生医療 / 再生医学 / 細胞・組織 / 生物・生体工学 / 肝細胞 / 胆管上皮細胞 / 球状凝集体 / 胆管 / 組織工学 / 極性 / スフェロイド / 胆管ネットワーク

Research Abstract

To organize implantable liver tissues having a functional bile duct network, first, we made spherical cellular aggregates constituted of fetal rat liver cells and mature bile duct epithelial cells isolated from rats. Aggregates having a continuous and functional bile duct network over the entire aggregates were successfully formed in the aggregates containing a three times larger number of mature bile duct cells over fetal liver cells. When such aggregates were immobilized in poly-L-lactic acid scaffolds with Matrigel and were implanted into the mesentery of immune-deficient mice, bile duct networks were well maintained in the case of aggregates having mature bile duct cells, whereas they were not formed in the case of pure fetal liver cell aggregates. These results showed that mature bile duct cells are necessary in forming functional bile duct networks over organized liver tissues.

Research Products

• [Journal Article] Biliaryepithelial cells play an essential role inthe reconstruction of hepatic tissue witha functional bile ductular network (2013)
  • Author(s): Takeshi Katsuda, N. Kojima, TakahiroOchiya, and Yasuyuki Sakai.
  • Journal Title: TissueEng. A Volume: in press.
  • Peer Reviewed
• [Journal Article] Hypoxiaefficiently induces differentiation ofmouse embryonic stem cells into endodermaland hepatic progenitor cells (2013)
  • Author(s): Takeshi Katsuda, Takumi Teratani,Mohammad,Mahfuz Chowdhury, TakahiroOchiya, Yasuyuki Sakai
  • Journal Title: Biochemical Engineering Journal Volume: 74 Pages: 95-101
  • Peer Reviewed
• [Journal Article] Hypoxia efficiently induces differentiation of mouse embryonic stem cells into endodermal and hepatic progenitor cells (2013)
  • Author(s): Takeshi Katsuda, Takumi Teratani, Mohammad Mahfuz Chowdhury, Takahiro Ochiya, Yasuyuki Sakai
  • Journal Title: Biochemical Engineering Journal Volume: 74 Pages: 95-101
  • DOI: 10.1016/j.bej.2013.02.012
  • Peer Reviewed
• [Journal Article] 脂肪由来幹細胞による細胞治療の可能性 (2011)
  • Author(s): 勝田 毅、酒井 康行、落谷 孝広
  • Journal Title: 実験医学 Volume: 29 Pages: 3102-3108
• [Journal Article] Transplantation of fetal livercell-loaded hyaluronic acid sponge ontothe mesentery recovers a Wilson' sdisease model rat (2010)
  • Author(s): Katsuda T, Teratani T, Ochiya T, SakaiY
  • Journal Title: J Biochem Volume: 148 Pages: 281-288
  • Peer Reviewed
• [Journal Article] 異所性体内埋め込み型人工肝臓開発の現状と展望 (2010)
  • Author(s): 勝田 毅、小森 喜久夫、寺谷 工、落谷孝広、酒井 康行
  • Journal Title: 生産研究 Volume: 62 Pages: 213-217
  • NAID: 130000342799
• [Journal Article] 間葉系幹細胞を用いた細胞治療の可能性 (2010)
  • Author(s): 勝田 毅、酒井 康行、落谷 孝広
  • Journal Title: 医工学治療 Volume: 22 Pages: 204-210
• [Journal Article] 1Yansplantation of a fetal liver ce11-loaded hyaluronic acid spongeonto the mesentery recovers a Wilson's disease model rat (2010)
  • Author(s): Katsuda T, Teratani T, OchiyaT, Sakai Y
  • Journal Title: J Biochem. Volume: 148 Pages: 281-288
  • Peer Reviewed
• [Journal Article] 異所性体内埋め込み型人工肝暇開発の現状と展望 (2010)
  • Author(s): 勝田毅, 小森喜久夫, 寺谷工, 落谷孝広, 酒井康行
  • Journal Title: 生産研究 Volume: 62 Pages: 213-217
• [Presentation] 胆管ネットワーク構造を配備した肝臓様組織のin vitro再構築 (2011)
  • Author(s): Katsuda T,Kojima N,Ochiya T,Sakai Y
  • Organizer: 第84回生化学会大会,
  • Place of Presentation: 京都.
  • Year and Date: 2011-09-21
• [Presentation] 胆管ネットワーク構造を配備した肝臓様組織のin vitro再構築 (2011)
  • Author(s): Katsuda T, Kojima N, Ochiya T, Sakai Y
  • Organizer: 第84回生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-21
• [Presentation] In vitro reconstruction of a liver-liketissue possessing a bile transport system,T (2011)
  • Author(s): Katsuda T,Kojima N,Ochiya T,Sakai Y,
  • Organizer: ERMIS-EU meeting
  • Place of Presentation: Granada,Spain
  • Year and Date: 2011-06-09
• [Presentation] In vitro reconstruction of a liver-like tissue possessing a bile transport system (2011)
  • Author(s): Katsuda T, Kojima N, Ochiya T, Sakai Y
  • Organizer: TERMIS-EU meeting
  • Place of Presentation: Granada, Spain
  • Year and Date: 2011-06-09
• [Presentation] 胆汁輸送機構を配備した肝臓様組織のin vitro再構築 (2011)
  • Author(s): 勝田 毅、小島 伸彦、落谷 孝広、酒井康行
  • Organizer: 第10回日本再生医療学会
  • Place of Presentation: 東京
  • Year and Date: 2011-03-02
• [Presentation] 胆汁輸送機構を配備した肝暇様組織のin vitro再構築 (2011)
  • Author(s): 勝田毅, 小島伸彦, 落谷孝広, 酒井康行
  • Organizer: 第10回日本再生医療学会
  • Place of Presentation: 東京
  • Year and Date: 2011-03-02
• [Book] Springer-Verlag UK,221 (2013)
  • Author(s): Y. Sakai, J. Jiang, S. Hanada, H. Huang,T.Katsuda, N. Kojima, T. Teratani, A.Miyajima, T.Ochiya
  • Total Pages: 221
  • Publisher: Fetal TissueTransplantation in Fetal TissueTransplantation
• [Book] Fetal Tissue Transplantation in Fetal Tissue Transplantation（分担執筆）, (2013)
  • Author(s): Y. Sakai1, J. Jiang, S. Hanada, H. Huang, T. Katsuda, N. Kojima, T. Teratani, A. Miyajima, T. Ochiya
  • Total Pages: 221
  • Publisher: Springer-Verlag UK
• [Book] in"Liver StemCells"etd. by T. Ochiya, Hamana Press (2011)
  • Author(s): Y.Sakai, M.Nishikawa, F.Evenou, M.Hamon,H.Huang, K.P.Montagne, N.Kojima, T.Fujiiand T.Niino
  • Total Pages: 236
  • Publisher: Engineering of implantableliver tissues
• [Book] "Engineering of implantable liver tissues", in "Liver Stem Cells"(etd.by T.Ochiya) (2011)
  • Author(s): Y.Sakai, M.Nishikawa, F.Evenou, M.Hamon, H.Huang, K.P.Montagne, N.Kojima, T.Fujii, T.Niino
  • Publisher: Hamana Press
• [Remarks]
  • URL: http://envchem.iis.u-tokyo.ac.jp/sakai/index.php?lang=ja&page=research&category=6