In vitro model tissue of interregional cortical connections

• Project/Area Number: 18K19903
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 90:Biomedical engineering and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Ikeuchi Yoshiho 東京大学, 生産技術研究所, 准教授 (30740097)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2018: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• Keywords: 神経 / 脳 / iPS細胞 / オルガノイド / 軸索 / 脳組織 / ヒトiPS細胞 / 分化 / 組織工学 / 回路 / 大脳

Outline of Final Research Achievements

This research project successfully developed a method to connect two or more cerebral organoids through axon bundles spontaneously extended from them and assembled. We confirmed that neuronal actives are exchanged between the organoids. This method could open up new studies to model neuronal circuits in the brain because the tissue bears both local and distant neuronal connections.

Academic Significance and Societal Importance of the Research Achievements

大脳は領域(領野)ごとに機能が異なる局所構造（回路）をもち、それらが互いに巨視的に繋がり合うことで機能することができる。本研究ではこの基本の回路構造を模倣することを目指した。本研究で開発した方法によって、局所的な神経回路と巨視的な神経回路の両方を同時に持たせた人工組織内を作ることができるようになった。今後さらに発展させることによって脳に似た神経回路を構築し、機能解析などを行うために活用されることが期待される。

Research Products

• [Int'l Joint Research] ボルドー大学(フランス)
• [Journal Article] A light-inducible Hedgehog signaling activator modulates proliferation and differentiation of neural cells. (2020)
  • Author(s): Ryuji Misawa, Tsuyoshi Minami, Akimitsu Okamoto, Yoshiho Ikeuchi.
  • Journal Title: ACS Chemical Biology Volume: - Issue: 6 Pages: 1595-1603
  • DOI: 10.1021/acschembio.0c00195
  • Peer Reviewed / Open Access
• [Journal Article] A Human Induced Pluripotent Stem Cell-Derived Tissue Model of a Cerebral Tract Connecting Two Cortical Regions. (2019)
  • Author(s): Kirihara T, Luo Z, Chow SYA, Misawa R, Kawada J, Shibata S, Khoyratee F, Vollette CA, Volz V, Levi T, Fujii T, Ikeuchi Y
  • Journal Title: iScience Volume: 14 Pages: 301-311
  • DOI: 10.1016/j.isci.2019.03.012
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] A three-dimensional in vitro model of interconnected cerebral regions (2018)
  • Author(s): Takaaki Kirihara, Jiro Kawada, Zhongyue Luo, Angela Chow, Ryuji Misawa, Farad Khoyratee, Timothee Levi, Teruo Fujii, Yoshiho Ikeuchi
  • Organizer: 第37回 化学とマイクロ・ナノシステム学会