Transplantation of human iPS cell derived neural cells on hemiplegic mice with experimental brain injury

• Project/Area Number: 26462172
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Wakisaka Sueshige 聖マリアンナ医科大学, 医学部, 講師 (80308527)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 再生医学 / 神経細胞移植 / Reelin / 片麻痺 / 運動神経 / 皮質運動野 / 一次運動神経 / ３次元組織 / 脳血管障害 / 皮質運動神経 / ヒトiPS細胞

Outline of Final Research Achievements

We have been conducting transplantation experiments on neural cells differentiated from human iPS cells to hemiplegic model mice.Reelin was identified as a protein that controls neuronal cell migration and layered structure formation of the motor cortex during development of humans.In our experimental system, inflammatory cells and transplanted cells in the brain both produced Reelin.The transplanted neural cells expressed receptors of Reelin. After binding of Reelin to its receptors they migrated to the injured cortex where the neural network was then reconstructed. The grafted neural stem / progenitor cells that migrated to the injured cortex were accompanied by their differentiation into the cortical motor neurons during the migration. In the neural cell transplantation to hemiplegic model animal, Reelin was shown to be important for histological repair and function recovery.

Research Products

• [Journal Article] Cellular and Molecular Mechanisms Governing Functional Recovery of Dementia Mice after Neuronal cell Transplantation. (2018)
  • Author(s): Suzuki N, Shimizu J, Takai K, Arimitsu N, Suzuki T, Fujiwara N.
  • Journal Title: Journal of Neuroscience and Neurosurgery. Volume: 1 Pages: 1-8
  • Peer Reviewed
• [Journal Article] Neuronal cell sheets of cortical motor neuron phenotype derived from human iPS cells. (2017)
  • Author(s): Suzuki N, Arimitsu N, Shimizu J, Takai K, Hirotsu C, Ueda Y, Wakisaka S, Fujiwara N, Suzuki T.
  • Journal Title: Cell Transplant. Volume: 26 Issue: 8 Pages: 1355-1364
  • DOI: 10.1177/0963689717720280
  • Peer Reviewed / Open Access
• [Journal Article] Generation of Retinal Progenitor Cell Sheets which Differentiate into Rhodopsin Positive Photoreceptors from Mouse iPS Cell Derived Retinal Progenitor Cell Clones. (2015)
  • Author(s): Noboru Suzuki, Jun Shimizu, Chieko Hirotsu, Erika Takada, Nagisa Arimitsu, Yuji Ueda, Naruyoshi Fujiwara, Tomoko Suzuki, Kenji Takai.
  • Journal Title: International Journal of Ophthalmology and Clinical Research Volume: 2 Pages: 1-5
  • Peer Reviewed / Open Access
• [Journal Article] Pax7 Gene Induction Rapidly Regulates Myocyte Homeostasis in Human Induced Pluripotent Stem (iPS) Cells. (2014)
  • Author(s): Misawa H, Saito A, Shimizu J, Iinuma M, Shiratsuchi T, Fujiwara N, Takai K, Arimitsu N, Ueda Y, Wakisaka S, Suzuki T, Beppu M, Suzuki N.
  • Journal Title: St. Marianna Medical Journal. Volume: 5 Pages: 59-67
  • Peer Reviewed
• [Presentation] Reelin Signal Activation is Associated With Motor Function Recovery in the Neuron Transplantation of Hemiplegic Mice. (2018)
  • Author(s): Nagisa Arimitsu, Jun Shimizu, Kenji Takai, Fujiwara Naruyoshi, Chieko Hirotsu, Yoko Okada , and Noboru Suzuki.
  • Organizer: the 51st Winter Conference on Brain Research (WCBR) .
  • Int'l Joint Research
• [Presentation] RESTORATION OF REELIN/APOER2 INTERACTION RESTORE COGNITIVE DYSFUNCTION OF DEMENTIA MODER MICE AFTER TRANSPLANTATIOB OF HUMAN IPS CELL-DERIVED NEURAL STEM/PRECURSOR CELLS. (2017)
  • Author(s): Fujiwara Naruyoshi, Takai Kenji, Shimizu Jun and Suzuki Noboru
  • Organizer: International society for stem cell research 13th annual meeting
  • Int'l Joint Research