The therapeutic potential of embryonic stem cell-derived neural progenitor cells for neonatal hypoxic-ischemic brain injury

• Project/Area Number: 24791504
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cerebral neurosurgery
• Research Institution: Yamaguchi University
• Principal Investigator: SHINOYAMA Mizuya 山口大学, 医学部, 特別医学研究員 (70467794)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 移植・再生医療 / 低酸素脳虚血 / 再生医学 / 神経科学 / 脳性麻痺 / 発生・分化

Research Abstract

In this study, I evaluated the ability of embryonic stem cell-derived neural progenitor cells (ES-NPCs) to become cortical deep layer neurons, to restore the neural network, and to repair brain damage in an HIE mouse model.
Forty-hours after the induction of HIE, animals were grafted with ES-NPCs targeting the deep layer of the motor cortex in the ischemic brain. Motor function was evaluated 3 weeks after transplantation.
As a result, The graft showed good survival and an appropriate innervation pattern via axonal sprouting from engrafted cells in the ischemic brain. The motor functions of the transplanted HIE mice also improved significantly compared to the sham-transplanted group. These findings suggest that cortical region specific engraftment of preconditioned cortical precursor cells could support motor functional recovery in the HIE model.

Research Products

• [Journal Article] Cortical region-specific engraftment of embryonic stem cell-derived neural progenitor cells restores axonal sprouting to a subcortical target and achieves motor functional recovery in a mouse model of neonatal hypoxic-ischemic brain injury. (2013)
  • Author(s): Mizuya Shinoyama, Makoto Ideguchi, Hiroyuki Kida, Koji Kajiwara, Yoshiteru Kagawa, Yoshihiko Maeda, Sadahiro Nomura, Michiyasu Suzuki
  • Journal Title: Frontiers in Cellular Neuroscience Volume: 7 Pages: 128-128
  • DOI: 10.3389/fncel.2013.00128
  • Peer Reviewed
• [Journal Article] The effect of hypothermia therapy in neonatal mice on the cortical laminar disruption following ischemic injury in neonatal mice. (2013)
  • Author(s): Kida, H., Nomura, S., Shinoyama, M., Ideguchi, M., Owada, Y. and Suzuki, M.
  • Journal Title: PLos One Volume: 8 Issue: 7 Pages: e68877-e68877
  • DOI: 10.1371/journal.pone.0068877
  • Peer Reviewed
• [Journal Article] The Effect of Hypothermia Therapy on Cortical Laminar Disruption following Ischemic Injury in Neonatal Mice. (2013)
  • Author(s): Hiroyuki Kida, Sadahiro Nomura, Mizuya Shinoyama, Makoto Ideguchi, Yuji Owada, Michiyasu Suzuki
  • Journal Title: PLoS ONE Volume: 8
  • Peer Reviewed
• [Journal Article] Fulminant Tuberculous Meningitis (2012)
  • Author(s): Mizuya Shinoyama, Michiyasu Suzuki, Sadahiro Nomura
  • Journal Title: Neurologia medico-chirurgica Volume: 52 Issue: 10 Pages: 761-764
  • DOI: 10.2176/nmc.52.761
  • NAID: 10030873536
  • ISSN: 0470-8105, 1349-8029
  • Peer Reviewed
• [Presentation] 低酸素性虚血マウスに対する胚性幹細胞由来神経前駆細胞移植 (2012)
  • Author(s): 篠山瑞也, 出口誠, 野村貞宏, 鈴木倫保
  • Organizer: 日本脳神経外科学会第71回学術総会
  • Place of Presentation: 大阪(大阪国際会議場)
  • Year and Date: 2012-10-17
• [Presentation] 低酸素性虚血マウスに対する胚性幹細胞由来神経前駆細胞移植 (2012)
  • Author(s): 篠山瑞也、出口 誠、野村貞宏、鈴木倫保
  • Organizer: 日本脳神経外科学会 第71回学術総会
  • Place of Presentation: 大阪国際会議場、大阪