Construction of the neural interface (neural microfiber bundle) by using the regenerative medicine

• Project/Area Number: 26630088
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Intelligent mechanics/Mechanical systems
• Research Institution: The University of Tokyo
• Principal Investigator: Negishi Midori 東京大学, 生産技術研究所, 研究員 (30300750)
• Co-Investigator(Kenkyū-buntansha): Hiroaki Onoe 慶應義塾大学, 理工学部, 講師 (30548681)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: マイクロ・ナノデバイス / マイクロマシン / 再生医療 / 神経移植 / 脳・神経 / 細胞・組織 / 神経科学

Outline of Final Research Achievements

In this research, we tried to make a neural interface which is formed from a neurons /neural stem cells and a biocompatible material for medical transplantation. We first established a stable construction method of the neural microfibers. Neural microfibers had the structure of the meters length and 100-200 μm diameter. Then, the bundles of 48 neural microfibers were made with collagen solution (collagen bundle), a combination of Na-alginate and amphiphilic chitosan solution (chitosan bundle), or fibrin sealant (fibrin bundle), cultured for 6 days after microfiber formation, and transplanted into the transected mouse spinal cord. The survival rate of the neural stem cells were monitored by in vivo bioluminescence imaging for 6 weeks after transplantation. Immunohistochemistry analysis demonstrated that the transplanted neural stem cells survived and migrated into the host spinal cord. The surviving neural stem cells differentiated into neurons, astrocytes, and oligodendrocytes.

Research Products

• [Journal Article] Differentiation Induction of Mouse Neural Stem Cells in Hydrogel Tubular Microenvironments with Controlled Tube Dimensions (2016)
  • Author(s): Hiroaki Onoe, Midori Kato-Negishi, Akane Itou and Shoji Takeuchi
  • Journal Title: Advanced Healthcare Materials Volume: online versione Issue: 9 Pages: 2192-2659
  • DOI: 10.1002/adhm.201500903
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Neural stem/progenitor cell-laden microfibers promote transplant survival in a mouse transected spinal cord injury model (2015)
  • Author(s): Keiko Sugai, Soraya Nishimura, Midori Kato-Negishi, Hiroaki Onoe, Shintaroh Iwanaga, Yoshiaki Toyama, Morio Matsumoto, Shoji Takeuchi, Hideyuki Okano and Masaya Nakamura
  • Journal Title: Journal of Neuroscience Research Volume: 93 Issue: 12 Pages: 1826-1838
  • DOI: 10.1002/jnr.23636
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Formation of complex 3D neural network by neural microfiber (2014)
  • Author(s): M. Kato-negishi, H. Onoe, S. Takeuchi
  • Organizer: Society for Neuroscience 2014
  • Place of Presentation: ワシントンD.C.、アメリカ
  • Year and Date: 2014-11-15
• [Presentation] Neural stem/progenitor cells-laden microfibers promote survival of transplants in mouse transected spinal cord injury model (2014)
  • Author(s): K. Hori, S. Nishimura, M. Kato-Negishi, H. Onoe, Y. Kobayashi, G. Itakura, H. Iwai, S. Takeuchi, H. Okano, Y. Toyama, M. Nakamura
  • Organizer: The 53rd ISCoS Annual Scientific Meeting
  • Place of Presentation: Maastricht, The Netherlands
  • Year and Date: 2014-09-02 – 2014-09-04
• [Presentation] Survival of neural stem/progenitor cells is promoted when cells are loaded in artificial microfibers in mouse complete spinal cord injury model (2014)
  • Author(s): K. Hori, S. Nishimura, M. Kato-Negishi, H. Onoe, Y. Kobayashi, G. Itakura, H. Iwai, S. Takeuchi, H. Okano, Y. Toyama, M. Nakamura
  • Organizer: ISSCR (International Society for Stem Cell Research) 12th Annual Meeting
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2014-06-18 – 2014-06-24