Establishment of a combination therapy with cell transplantation and rehabilitation at chronic phase after spinal cord injury

• Project/Area Number: 24592188
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: ENOMOTO Mitsuhiro 東京医科歯科大学, 医学部附属病院, 講師 (90451971)
• Co-Investigator(Kenkyū-buntansha): WAKABAYASHI Yoshiaki 東京医科歯大学, 大学院医歯学総合研究科, 講師 (00431916) ; SOTOME Shinichi 東京医科歯大学, 大学院医歯学総合研究科・寄付講座, 准教授 (20401391) ; OKAWA Atsushi 東京医科歯大学, 大学院医歯学総合研究科, 教授 (30251507)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 脊髄損傷 / 細胞移植 / 人工担体 / リハビリテーション

Outline of Final Research Achievements

We believe that a combination therapy with cell transplantation and rehabilitation is best because the cells can work directly to repair the injured environment and the rehabilitation can activate neural plasticity. The rehabilitative effects of treadmill running (TM) and swimming (SW) during the chronic phase in rats with a SCI were evaluated. Six weeks after the contusion injury at the thoracic level, the TM group showed improved hind limb coordination, and gait length in the TM group was longer than that of the control group. In both TM and SW group, the mRNA levels of NT-3 and PSD95 were increased compared to the control group. Even long after a SCI, the spinal cord has a high capacity for neural plasticity. However, behavioral recovery was not sufficient after BMSC transplantation with scaffold at six weeks after SCI. The further tissue damage occurred by the direct implantation. Further analysis is needed to obtain successful recovery at the chronic phase after SCI.

Research Products

• [Journal Article] Bone marrow stromal cells combined with a honeycomb collagen sponge facilitate neurite elongation in vitro and neural restoration in the hemisected rat spinal cord (2014)
  • Author(s): Ukegawa M, Bhatt K, Hirai T, Kaburagi H, Sotome S, Wakabayashi Y, Ichinose S, Shinomiya K, Okawa A, Enomoto M
  • Journal Title: Cell Transplant Volume: 6
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Intrathecal AAV Serotype 9-mediated Delivery of shRNA Against TRPV1 Attenuates Thermal Hyperalgesia in a Mouse Model of Peripheral Nerve Injury. (2014)
  • Author(s): Hirai T, Enomoto M, Kaburagi H, Sotome S, Yoshida-Tanaka K, Ukegawa M, Kuwahara H, Yamamoto M, Tajiri M, Miyata H, Hirai Y, Tominaga M, Shinomiya K, Mizusawa H, Okawa A, Yokota T
  • Journal Title: Mol Ther Volume: 22 Issue: 2 Pages: 409-19
  • DOI: 10.1038/mt.2013.247
  • Peer Reviewed
• [Journal Article] Dynamic changes in spinal cord compression by cervical ossification of the posterior longitudinal ligament evaluated by kinematic computed tomography myelography (2014)
  • Author(s): Yoshii T, Yamada T, Hirai T, Taniyama T, Kato T, Enomoto M, Inose H, Sumiya S, Kawabata S, Shinomiya K, Okawa A.
  • Journal Title: Spine Volume: 39 Issue: 2 Pages: 113-9
  • DOI: 10.1097/brs.0000000000000086
  • NAID: 40020700037
  • Peer Reviewed
• [Journal Article] Efficacy of biphasic transcranial electric stimulation in intraoperative motor evoked potential monitoring for cervical compression myelopathy. (2014)
  • Author(s): Ukegawa D, Kawabata S, Sakaki K, Ishii S, Tomizawa S, Inose H, Yoshii T, Kato T, Enomoto M, Okawa A.
  • Journal Title: Spine Volume: 39 Issue: 3 Pages: E159-E165
  • DOI: 10.1097/brs.0000000000000082
  • Peer Reviewed
• [Journal Article] A multifunctional neurotrophin with reduced affinity to p75NTR enhances transplanted Schwann cell survival and axon growth after spinal cord injury. (2013)
  • Author(s): Enomoto M, Bunge MB, Tsoulfas P.
  • Journal Title: Exp Neurol. Volume: 248 Pages: 170-82
  • DOI: 10.1016/j.expneurol.2013.06.013
  • Peer Reviewed
• [Journal Article] Sema3A regulates bone-mass accrual through sensory innervations (2013)
  • Author(s): Fukuda T, Takeda S, Xu R, Ochi H, Sunamura S, Sato T, Shibata S, Yoshida Y, Gu Z, Kimura A, Ma C, Xu C, Bando W, Fujita K, Shinomiya K, Hirai T, Asou Y, Enomoto M, Okano H, Okawa A, Itoh H
  • Journal Title: Nature. Volume: 497 Issue: 7450 Pages: 490-493
  • DOI: 10.1038/nature12115
  • Peer Reviewed
• [Journal Article] Porous/dense composite hydroxyapatite for anterior cervical discectomy and fusion (2013)
  • Author(s): Yoshii T, Yuasa M, Sotome S, Yamada T, Sakaki K, Hirai T, Taniyama T, Inose H, Kato T, Arai Y, Kawabata S, Tomizawa S, Enomoto M, Shinomiya K, Okawa A
  • Journal Title: Spine (Phila Pa 1976) Volume: 38(10) Issue: 10 Pages: 833-40
  • DOI: 10.1097/brs.0b013e3182801390
  • Peer Reviewed
• [Journal Article] Modified K-line in magnetic resonance imaging predicts insufficient decompression of cervical laminoplasty. (2013)
  • Author(s): Taniyama T
  • Journal Title: Spine Volume: 2013 Mar 15;38(6) Issue: 6 Pages: 496-501
  • DOI: 10.1097/brs.0b013e318273a4f7
  • Peer Reviewed
• [Journal Article] Intrathecal shRNA-AAV9 inhibits target protein expression in the spinal cord and dorsal root ganglia of adult mice. (2012)
  • Author(s): Hirai T, Enomoto M, Machida A, Yamamoto M, Kuwahara H, Tajiri M, Hirai Y, Sotome S, Mizusawa H, Shinomiya K, Okawa A, Yokota T.
  • Journal Title: Hum Gene Ther Methods Volume: 23 Issue: 2 Pages: 119-27
  • DOI: 10.1089/hgtb.2012.035
  • Peer Reviewed
• [Journal Article] Increase in paravertebral muscle activity in lumbar kyphosis patients by surface electromyography compared with lumbar spinal canal stenosis patients and healthy volunteers. (2012)
  • Author(s): Enomoto M, Ukegawa D, Sakaki K, Tomizawa S, Arai Y, Kawabata S, Kato T, Yoshii T, Shinomiya K, Okawa A.
  • Journal Title: J Spinal Disord Tech Volume: 25 Issue: 6 Pages: 167-73
  • DOI: 10.1097/bsd.0b013e31825d63c4
  • Peer Reviewed
• [Presentation] An EGFR inhibitor induces Schwann cell proliferation and promotes functional recovery with remyelination in injured proneal nerve after end-to-side neurorrhaphy. (2014)
  • Author(s): M. Enomoto, M. Ukegawa, H. Kaburagi, T. Hirai, K. Yagishita, A. Okawa, Y. Wakabayashi
  • Organizer: The 44th annual meeting of the Society for Neuroscience
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2014-10-19
• [Presentation] 脊磁図による頸椎椎間孔の神経活動の可視化 (2014)
  • Author(s): 角谷 智, 川端 茂徳, 牛尾 修太, 請川 大, 猪瀬 弘之, 吉井 俊貴, 加藤 剛, 榎本 光裕, 大川 淳
  • Organizer: 第29回日本整形外科学会基礎学術集会
  • Place of Presentation: 鹿児島
  • Year and Date: 2014-10-10
• [Presentation] TRPV1を標的としたshRNA-AAV9くも膜下腔投与は神経障害性疼痛マウスの熱刺激過敏を有意に抑制する (2014)
  • Author(s): 平井 高志, 榎本 光裕, 鏑木 秀俊, 早乙女 進一, 四宮 謙一, 横田 隆徳, 大川 淳
  • Organizer: 第29回日本整形外科学会基礎学術集会
  • Place of Presentation: 鹿児島
  • Year and Date: 2014-10-10
• [Presentation] 腰椎変性疾患を有する高齢者の腰背筋活動と多裂筋変性との関係 (2014)
  • Author(s): 榎本 光裕, 請川 大, 加藤 剛, 吉井 俊貴, 猪瀬 弘之, 小柳津 卓哉, 川端 茂徳, 大川 淳
  • Organizer: 第43回日本脊椎脊髄病学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2014-04-18
• [Presentation] Expression patterns of glial cell-derived neurotrophic factor, vascular endothelial growth factor and their receptors after rat spinal cord injury (2013)
  • Author(s): M. Enomoto, R. Yamashita, M. Ukegawa, H. Kaburagi, T. Hirai, K. Yagishita, A. Okawa
  • Organizer: The 43th annual meeting of the Society for Neuroscience
  • Place of Presentation: サンディエゴ、USA
• [Presentation] Intrathecal AAV serotype 9-mediated delivery of shRNA against TRPV1 attenuates thermal hyperalgesia in a mouse model of peripheral nerve injury (2013)
  • Author(s): T. Hirai, M. Enomoto, H. Kaburagi, S. Sotome, K. Shinomiya, A. Okawa, T. Yokota
  • Organizer: The 43th annual meeting of the Society for Neuroscience
  • Place of Presentation: サンディエゴ、USA
• [Presentation] 脊髄損傷慢性期における移植骨髄間葉系細胞の役割 (2013)
  • Author(s): 山下 理子, 榎本 光裕, 請川 円, 鏑木 秀俊, 早乙女 進一, 大川 淳
  • Organizer: 第28回日本整形外科学会基礎学術集会
  • Place of Presentation: 千葉県千葉市、幕張メッセ
• [Presentation] ラット脊髄損傷慢性期に対する運動療法の効果 (2012)
  • Author(s): 島田皓子, 請川円, 平井高志, 堀江正樹, 柳下和慶, 大川淳, 榎本光裕
  • Organizer: 第27回 日本整形外科学会基礎学術集会
  • Place of Presentation: 名古屋
• [Presentation] ラット脊髄損傷慢性期におけるトレッドミル運動効果が脊髄での神経栄養因子とシナプス関連タンパクに与える影響 (2012)
  • Author(s): 請川円 平井高志 鏑木秀俊 大川淳 榎本光裕
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋
• [Presentation] Both treadmill exercise and swimming induce increase of neurotrophic factors and synaptic proteins at the chronic phase after spinal cord injury (2012)
  • Author(s): M. ENOMOTO， A. SHIMADA, M. UKEGAWA, T. HIRAI, Y. WAKABAYASHI, M. HORIE, A. OKAWA, K. YAGISHITA
  • Organizer: The 42th annual meeting of the Society for Neuroscience
  • Place of Presentation: ニューオリンズ 米国
• [Book] Neuroprotection and Regeneration of the Spinal Cord (2014)
  • Author(s): Mitsuhiro Enomoto, Madoka Ukegawa, Kazuyuki Fukushima, Kush Bhatt, Yoshiaki Wakabayashi, Atsushi Okawa
  • Total Pages: 419
  • Publisher: Springer
• [Book] PAIN MANAGEMENT FOLLOWING SPINAL CORD INJURY: CLINICAL AND BASIC SCIENCE PERSPECTIVES (2012)
  • Author(s): Mitsuhiro Enomoto and Aldric T. Hama
  • Total Pages: 39
  • Publisher: Nova Science Publishers, Inc
• [Remarks] 東京医科歯科大学整形外科
  • URL: http://www.tmd.ac.jp/med/orth/
• [Remarks] 東京医科歯科大学整形外科
  • URL: http://www.tmd.ac.jp/med/orth/
• [Remarks] 東京医科歯科大学整形外科
  • URL: http://www.tmd.ac.jp/med/orth/