Intraventricular pulsatile injection of trophic factors in mice model of ALS

• Project/Area Number: 16K09719
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Tottori University
• Principal Investigator: WATANABE Yasuhiro 鳥取大学, 医学部, 講師 (20335540)
• Research Collaborator: HONDA Naoto ; TOKUOKA Yuta
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 筋萎縮性側索硬化症 / 神経栄養因子 / 細胞移植 / 細胞シート / 筋萎縮性側索症 / 神経細胞死 / 神経成長因子

Outline of Final Research Achievements

1.Sustained delivery of neurotrophic factors to mice brain.　We developed HAC-MSCs which highly expressed neurotrophic factors. Transplanting this cells as a monolayer sheet structure, we confirmed this method is so far the most promising way to deliver the trophic factors to mice brain. Howerver, the HAC-MSC sheet eliminated from host tissue in a quite short term after the transplantation. We considered controlling this immune-rejection is necessary for further improvement of the efficacy of transplantation.
2.Establishing the method to detect cell survival signals efficiently.　We observed that the host microglial cells are numerously infiltrating into transplanted cell sheet structure. We also confirmed these infiltrating microglias are both cytoprotective (M2) and cytotoxic (M1) populations. By selectively eliminate the host microglias, we are examining this procedure improve the survival of the transplanted cell sheet.

Academic Significance and Societal Importance of the Research Achievements

現在有効な治療法のない筋萎縮性側索硬化症の基礎的な研究を行った．本検討が即座に疾患の治療に繋がるわけではないが，細胞治療の可能性と方向性を拡げるものである．実際の臨床応用に関して，さらに安全性と有効性の評価を進める必要があると考え，それを実践している．

Research Products

• [Journal Article] Tetanus toxin fragments and Bcl-2 fusion proteins: cytoprotection and retrograde axonal migration. (2018)
  • Author(s): Watanabe Y, Matsuba T, Nakanishi M, Une M, Hanajima R, Nakashima K.
  • Journal Title: BMC Biotechnol. Volume: 18 Issue: 1 Pages: 39-39
  • DOI: 10.1186/s12896-018-0452-z
  • Peer Reviewed / Open Access
• [Journal Article] Cowden Syndrome with a Novel <i>PTEN</i> Mutation Presenting with Partial Epilepsy Related to Focal Cortical Dysplasia (2018)
  • Author(s): Adachi T, Takigawa H, Nomura T, Watanabe Y, Kowa H
  • Journal Title: Internal Medicine Volume: 57 Issue: 1 Pages: 97-99
  • DOI: 10.2169/internalmedicine.9052-17
  • NAID: 130006301270
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 下肢筋力低下で発症しSOD1L126S変異を認めた家族性筋萎縮性側索硬化症の3例 (2017)
  • Author(s): 種田健太，足立正，足立芳樹，渡辺保裕，花島律子
  • Journal Title: 神経内科 Volume: 87 Pages: 545-549
  • Peer Reviewed
• [Journal Article] Structural basis of Cu, Zn-superoxide dismutase amyloid fibril formation involves interaction of multiple peptide core regions (2016)
  • Author(s): Ida, M. Ando, M. Adachi, M. Tanaka, A. Machida, K. Hongo, K. Mizobata, T. Yamakawa, M. Y. Watanabe, Y. Nakashima, K. Kawata, Y.
  • Journal Title: Journal of Biochemistry Volume: 159 Issue: 2 Pages: 247-260
  • DOI: 10.1093/jb/mvv091
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Anthocyanin suppresses the toxicity of Abeta deposits through diversion of molecular forms in in vitro and in vivo models of Alzheimer's disease (2016)
  • Author(s): Yamakawa, M. Y. Uchino, K. Watanabe, Y. Adachi, T. Nakanishi, M. Ichino, H. Hongo, K. Mizobata, T. Kobayashi, S. Nakashima, K. Kawata, Y.
  • Journal Title: Nutritional Neuroscience Volume: 19 Issue: 1 Pages: 32-42
  • DOI: 10.1179/1476830515y.0000000042
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Japanese version of the ALS-FTD-Questionnaire (ALS-FTD-Q-J). (2016)
  • Author(s): Watanabe Y, et al.
  • Journal Title: J Neurol Sci Volume: 367 Pages: 51-55
  • DOI: 10.1016/j.jns.2016.05.036
• [Presentation] 細胞シート状態で大脳へ移植した間葉系幹細胞の生着に関与する因子の検討． (2019)
  • Author(s): 本多直人，渡辺保裕，花島 律子，寺嶋智也
  • Organizer: 第18回日本再生医療学会総会
• [Presentation] The ability of retrograde axonal migration and neuroprotection of tetanus toxin fragments and Bcl2 fusion proteins (2017)
  • Author(s): Watanabe Y, Nakanishi M, Une M, Nakashima K
  • Organizer: 23rd World Congress of Neurology
  • Int'l Joint Research
• [Presentation] Efficacy of long-term engraftment of modified MSCs in a mouse model of ALS - use of cell-sheet technology (2017)
  • Author(s): Nakanisi M, Une M, Watanabe Y Nakashima K, Hanajima R
  • Organizer: 28th International Symposium on ASL/MND
  • Int'l Joint Research
• [Presentation] Identification of protein-interacting Cu/Zn superoxide dismutase (SOD1): participation of the SOD1 aggregation core and the protein degradation system (2017)
  • Author(s): Une M, Yamakawa M, Nakanishi M, Kawata Y, Watanabe Y, Nakashima K, Hanajima R
  • Organizer: 28th International Symposium on ASL/MND
  • Int'l Joint Research
• [Presentation] Rretrograde axonal migration and neuroprotection of tetanus toxin fragments and Bcl2 fusion proteins (2017)
  • Author(s): Watanabe Y, Matsuba T, Nkanishi M, Une M, Hnajima R
  • Organizer: 28th International Symposium on ASL/MND
  • Int'l Joint Research