Development of combination strategies with selective cell therapyand multineurotrophin for spinal cord injury at chronic phase

• Project/Area Number: 19890068
• Research Category: Grant-in-Aid for Young Scientists (Start-up)
• Allocation Type: Single-year Grants
• Research Field: Orthopaedic surgery
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: ENOMOTO Mitsuhiro Tokyo Medical and Dental University, 大学院・医歯学総合研究科, 寄附講座講師 (90451971)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥2,947,000 (Direct Cost: ¥2,560,000、Indirect Cost: ¥387,000); Fiscal Year 2008: ¥1,677,000 (Direct Cost: ¥1,290,000、Indirect Cost: ¥387,000); Fiscal Year 2007: ¥1,270,000 (Direct Cost: ¥1,270,000)
• Keywords: 脊髄損傷 / 細胞移植 / 神経栄養因子 / 神経再生

Research Abstract

成ラット胸髄に血管クリップを用いた圧挫損傷モデルを作製し、損傷6週で損傷脊髄部分に培養したFGF2反応性神経前駆細胞の移植を行った。その結果、GFP遺伝子導入の細胞移植群(対照群)より、NT3とBDNFの作用を持った改変NT3をさらにp75受容体に結合しにくい構造に改変した神経栄養因子遺伝子を導入した細胞移植群のほうが後肢運動機能の改善を認めた。移植細胞の生着は、対照群と比較して栄養因子導入細胞で1.8倍高く残存ミエリンも多かった。脊髄損傷慢性期での細胞移植は、細胞単独では機能回復に不十分であり本研究のように神経栄養因子を組み合わせた治療が必要なことが明らかとなった。

Research Products

• [Journal Article] The axonal regeneration across a honeycomb collagen sponge applied to the transected spinal cord (2008)
  • Author(s): Fukushima K, Enomoto M, Tomizawa S, Takahashi M, Wakabayashi Y, Itoh S, Kuboki Y and Shinomiya K
  • Journal Title: J Med Dent Sci 55 Pages: 71-79
  • NAID: 120006409954
• [Journal Article] Co-overexpression of GDNF and GFRα1 induces neural differentiation in neural progenitor cells in comparison to bone marrow stromal cells (2008)
  • Author(s): Nojiri Y, Takeda S, Enomoto M, Nishitsuji H, Masuda T, Sotome S and Shinomiya K
  • Journal Title: J Med Dent Sci 55 Pages: 121-128
  • NAID: 120006409959
• [Journal Article] The Axonal Regeneration Across a Honeycomb Collagen Sponge Applied to the Transected Spinal Cord (2008)
  • Author(s): Fukushima K, Enomoto M
  • Journal Title: J Med Dent Sci 55 Pages: 71-79
  • NAID: 120006409954
  • Peer Reviewed
• [Journal Article] Co-overexpression of GDNF and GFRα1 induces neural differentiation in neural progenitor cells in comparison to bone marrow stromal cells (2008)
  • Author(s): Nojiri Y, Takeda S, Enomoto M
  • Journal Title: J Med Dent Sci 55 Pages: 121-128
  • NAID: 120006409959
  • Peer Reviewed
• [Presentation] Schwann cells improve survival of embryonic neurons transplanted into theaxotomized eibial nerve and promote muscle reinnervation (2008)
  • Author(s): Enomoto M, Grumbles RM, Almeida VW, Tsoulfas P, Casella GTB, Wang Y, Wood PM and Thomas CK
  • Organizer: The 38th annual meeting of the Society for Neuroscience
  • Year and Date: 2008-11-18
• [Presentation] Schwann cells improve survival of embryonic neurons transplanted into the axotomized tibial nerve and promote muscle reinnervation (2008)
  • Author(s): 榎本光裕
  • Organizer: 北米神経科学大会
  • Place of Presentation: 米国
  • Year and Date: 2008-11-18
• [Presentation] Clip compressionによるラット胸髄損傷の運動機能回復と組織学的評価 (2008)
  • Author(s): 草野和生, 榎本光裕, 早乙女進一, 四宮謙一
  • Organizer: 第23回日本整形外科学会基礎学術集会
  • Year and Date: 2008-10-24
• [Presentation] Clip compressionによるラット胸髄損傷の運動機能回復と組織学的評価 (2008)
  • Author(s): 草野和生, 榎本光裕
  • Organizer: 第23回日本整形外科学会基礎学術集会
  • Place of Presentation: 京都
  • Year and Date: 2008-10-24
• [Presentation] A multifunctionalneurotrophin missing the p75NGFR activity, enhances Schwann cell survival and axon growthafter spinal cord injury (2007)
  • Author(s): Enomoto M and Tsoulfas P
  • Organizer: The 37th annual meeting of the Society for Neuroscience
  • Year and Date: 2007-11-06
• [Presentation] A multifunctional neurotrophin missing the p75NGFR activity, enhances Schwann cell survival and axon growth after spinal cord injury (2007)
  • Author(s): 榎本光裕
  • Organizer: 北米神経科学大会
  • Place of Presentation: 米国
  • Year and Date: 2007-11-06
• [Presentation] 損傷脊髄に対するシュワン細胞移植と異なるレセプター結合能をもつNT-3の効果 (2007)
  • Author(s): 榎本光裕, 四宮謙一, PantelisTsoulfas
  • Organizer: 第22回日本整形外科学会基礎学術集会
  • Year and Date: 2007-10-25
• [Presentation] 損傷脊髄に対するシュワン細胞移植と異なるレセプター結合能をもつNT-3の効果 (2007)
  • Author(s): 榎本光裕
  • Organizer: 第22回日本整形外科学会基礎学術集会
  • Place of Presentation: 浜松
  • Year and Date: 2007-10-25