整形外科教室

  • ごあいさつ
  • 組織
  • 脊椎・脊髄グループ
  • 上肢グループ
  • 下肢グループ
  • 骨・軟部腫瘍グループ
  • スポーツグループ
  • 基礎研究グループ
    • 脊髄再生
    • 運動器科学
    • バイオメカニクス
    • 筋生物
    • 軟骨椎間板
  • 実績
  • 沿革
  • 学生教育・大学院
  • 留学
  • 医局風景・イベント
  • 関連リンク・関連学会
  • 学会・研究会
  • 臨床研究

ENGLISH

基礎研究グループ

脊髄再生

研究室主任 中村 雅也
概要

神経解剖学者Ramon y Cajalが「成体哺乳類の中枢神経系は一度損傷を受けると再生しない」と述べて以来、中枢神経である脊髄の損傷は治らないと信じられてきました。脊髄損傷は広範な知覚・運動・自律神経系のダメージをもたらし、医学が目覚ましい進歩を遂げた現在でも、有効な治療方法は確立されていません。我々は脊髄損傷に対する再生医療の戦略として神経幹細胞やiPS細胞 (induced pluripotent stem cells)を用いた細胞移植療法を中心にその有効性を報告してきました。さらに、詳細な画像診断ツールの開発やリハビリテーションとの併用など、脊髄再生を目指して様々な面から包括的な研究を試みています。

実績紹介

臨床における脊髄損傷の現状

従来の手術療法では脊髄の再生は困難であった。

サル損傷脊髄に対するヒト神経幹細胞移植

移植により神経再生と運動機能回復が認められた。

iPS細胞由来神経幹細胞による治療

iPS細胞から神経幹細胞への誘導に成功。移植による有効性を確認。

損傷脊髄の画像評価の進歩

損傷脊髄の神経回路を可視化。治療効果の判定に応用。

正常脊髄(上段)と脊髄半切モデル(下段)での神経投射路選択的DTT

脊髄損傷の再生を促すリハビリ

リハビリテーションによる機能回復のメカニズム解明。

業績(カッコ内はインパクトファクター)

Itakura G, Kobayashi Y, Nishimura S, Iwai H, Takano M, Iwanami A, Toyama Y, Okano H, Nakamura M. Control of the survival and growth of human glioblastoma grafted into the spinal cord of mice by taking advantage of immunorejection. Cell Transplantation 10(2): 116413, 2015

Itakura G, Kobayashi Y, Nishimura S, Iwai H, Takano M, Iwanami A, Toyama Y, Okano H, Nakamura M. Controlling immune rejection is a fail-safe system against potential tumorigenicity after human iPSC-derived neural stem cell transplantation. PLoS ONE 10(2): 116413, 2015

Sugai K, Nishimura S, Kato-Negishi M, Onoe H, Iwanaga S, Toyama Y, Matsumoto M, Takeuchi S, Okano H, Nakamura M. Neural stem/progenitor cell-laden microfibers promote transplant survival in a mouse transected spinal cord injury model. Journal of Neuroscience Research 93: 1826-1838, 2015

Nori S, Okada Y, Nishimura S, Sasaki T, Itakura G, Kobayashi Y, Renault-Mihara F, Shimizu A, Koya I, Yoshida R, Kudoh J, Koike M, Uchiyama Y, Ikeda E, Toyama Y, Nakamura M, Okano H. Long-Term Safety Issues of iPSC-Based Cell Therapy in a Spinal Cord Injury Model: Oncogenic Transformation with Epithelial-Mesenchymal Transition. Stem Cell Reports 4: 360-373, 2015

Iwai H, Nori S, Nishimura S, Yasuda A, Takano M, Tsuji O, Fujiyoshi K, Toyama Y, Okano H, Nakamura M. Transplantation of neural stem/progenitor cells at different locations in mice with spinal cord injury. Cell Transplant. 23, 11: 1451-1464, 2014. (3.570)

Nishimura S, Sasaki T, Shimizu A, Yoshida K, Iwai H, Koya I, Kobayashi Y, Itakura G, Shibata S, Ebise H, Horiuchi K, Kudoh J, Toyama Y, Anderson AJ, Okano H, Nakamura M. Global gene expression analysis following spinal cord injury in non-human primates. Experimental Neurology. 261: 171-179, 2014. (4.617)

Takano M, Kawabata S, Komaki Y, Shibata S, Hikishima K, Toyama Y, Okano H, Nakamura M. Inflammatory cascades mediate synapse elimination in spinal cord compression. Journal of Neuroinflammation. 4: 11-40, 2014. (4.902)

Iida T, Nakamura M, Tsuji O, Iwanami A, Mikami S, Toyama Y, Chiba K, Matsumoto M. Dumbbell mesenchymal chondrosarcoma: report of a rare case. J Orthop Sci. 19: 190-193, 2014 Jan. (1.008)

Shinozaki M, Nakamura M, Konomi T, Kobayashi Y, Takano M, Saito N, Toyama Y, Okano H. Distinct roles of endogenous vascular endothelial factor receptor 1 and 2 in neural protection after spinal cord injury. Neurosci Res. 78: 55-64, 2014 Jan. (2.145)

Zhang L, Kaneko S, Kikuchi K, Sano A, Maeda M, Kishino A, Shibata S, Mukaino M, Toyama Y, Liu M, Kimura T, Okano H, Nakamura M. Rewiring of regenerated axons by combining treadmill training with semaphorin3A inhibition. Mol Brain. 7: 14, 2014 Mar. (4.345)

Nakamura M, Nishiwaki Y, Ushida T, Toyama Y. Prevalence and chracteristics of chronic muscloskeletal pain in Japan: A second survery of people with or without chronic pain. J Orthop Sci. 19: 339-350, 2014 Mar. (1.008)

Sumitani M, Yasunaga H, Uchida K, Horiguchi H, Nakamura M, Ohe K, Fushima K, Matsuda S, Yamada Y. Perioperative factors affecting the occurrence of acute complex regional pain syndrome following limb bone fracture surgery: Data from the Japanese Diagnosis Procedure Combination database. Rheumatology. 53: 1186-1193, 2014 Jul. (4.435)

Nagoshi N, Iwanami A, Toyama Y, Nakamura M. Factors contributing to improvement of syringomyelia after foramen magnum decompression for Chiari type I malNakamura M, Nishiwaki Y, Ushida T, Toyama Y. Prevalence and characteristics of chronic musculoskeletal pain in Japan: a second survey of people with or without chronic pain. J Orthop Sci. 19: 339-350, 2014 Mar. (1.008)formation. J Orthop Sci. 19: 418-423, 2014 May. (1.008)

Nakamura M, Nishiwaki Y, Ushida T, Toyama Y. Prevalence and characteristics of chronic musculoskeletal pain in Japan: a second survey of people with or without chronic pain. J Orthop Sci. 19: 339-350, 2014 Mar. (1.008)

Nakamura M, Nishiwaki Y, Sumitani M, Ushida T, Yamashita T, Konno S, Taguchi T, Toyama Y. Investigation of chronic musculoskeletal pain (third report): with special reference to the importance of neuropathic pain and psychogenic pain. J Orthop Sci. 19: 667-675, 2014 Jul. (1.008)

Shirasawa H, Ishii K, Iwanami A, Mikami S, Toyama Y, Matsumoto M, Nakamura M. Pediatric myxopapillary ependymoma treated with subtotal resection and radiation therapy: a case report and review of the literature. Spinal Cord. 52 Suppl 2: S18-20, 2014 Aug. (1.699)

Kondo T, Funayama M, Tsukita K, Hotta A, Yasuda A, Nori S, Kaneko S, Nakamura M, Takahashi R, Okano H, Yamanaka S, Inoue H. Focal transplantation of human iPSC-derived glial-rich neural progenitors improves lifespan of ALS mice. Stem Cell Reports. 12: 242-249, 2014 Aug.

Wu Z, Iwanami A, Yasuda A, Mikami S, Toyama Y, Nakamura M. Intramedullary cervicothoracic subependymoma: report of three cases and review of the literature. J Orthop Sci. epub, 2014 May. (1.008)

Sumitani M, Kogure T, Nakamura M, Shibata M, Yozu A, Otake Y, Yamada Y. Classification of the pain nature of CRPS type 1, based on patient complaints, into neuropathic pain and nociceptive/inflammatory pain, using the McGill Pain Questionnaire. J Anesthesia. in press 2014. (1.117)

Okada E, Nakamura M, Koshida Y, Mukai K, Toyama Y, Matsumoto M. Breast carcinoma metastasis to meningioma in the thoracic spine: A case report and review of the literature. J Spinal Cord Med. epub, 2014 Mar. (1.878)

Tashiro S, Shinozaki M, Mukaino M, Renault-Mihara F, Toyama Y, Liu M, Nakamura M, Okano H. BDNF Induced by Treadmill Training Contributes to theSuppression of Spasticity and Allodynia After Spinal Cord Injury via Upregulationof KCC2. Neurorehabil Neural Repair. epub, 2014 Dec. (4.617)

Nagoshi N, Suda K, Morita T, Matsumoto S, Iimoto S, Yasui K, Komatsu M, Kobayashi Y, Minami A, Toyama Y, Matsumoto M, Nakamura M. C1 posterior arch screw as an auxiliary anchor in posterior reconstruction for atlantoaxial dislocation associated with type II odontoid fracture: a case report and review of the literature. Springerplus. Epub, 2014 Nov.

Itakura G, Kobayashi Y, Nishimura S, Iwai H, Takano M, Iwanami A, Toyama Y, Okano H, Nakamura M. Control of the survival and growth of human glioblastoma grafted into the spinal cord of mice by taking advantage of immunorejection. Cell transplantation. epub, 2014 May. (3.570)

Nakamura M, Ushida T, Toyama Y. Reply to letter to the editor by Toda. J Orthop Sci. epub, 2014 Nov. (1.008)

Nishikawa R, Hotta R, Shimojima N, Shibata S, Nagoshi N, Nakamura M, Matsuzaki Y, Okano HJ, Kuroda T, Okano H, Morikawa Y. Migration and differentiation of transplanted enteric neural crest-derived cells in murine model of Hirschsprung's disease. Cytotechnology. epub, 2014 Sep. (1.449)

Iwanami A, Kobayashi Y, Takano M, Mikami S, Toyama Y, Nakamura M. Invasive dumbbell spinal meningiomas: report of four cases and a review of the literature. J Orthop Sci. epub, 2014 Sep. (1.008)

Kobayashi Y, Iwanami A, Tsuji O, Takano M, Kimura T, Toyama Y, Nakamura M. Extramedullary non-myxopapillary ependymoma of the cauda equina; a case report and review of the literature. J Spine & Neurosurg. in press 2014.

Itakura G, Kobayashi Y, Nishimura S, Iwai H, Takano M, Iwanami A, Toyama Y, Okano H, Nakamura M. Controlling immune rejection is a fail-safe system against potential tumorigenicity after human iPSC-derived neural stem cell transplantation. PLoS One. in press 2014. (3.534)

Nori S, Okada Y, Nishimura S, Sasaki T, Itakura G, Kobayashi Y, Renault-Mihara F, Shimizu A, Koya I, Yoshida R, Kudoh J, Koike M, Uchiyama Y, Ikeda E, Toyama Y, Nakamura M, Okano H. Long-term safety issues of iPSC-based cell therapy in a spinal cord injury model: oncogenic transformation with epithelial- mesenchymal transition. Stem Cell Reports. in press 2014.

Matsui T, Akamatsu W, Nakamura M, Okano H. Regeneration of the damaged central nervous system through reprogramming technology: basic concepts and potential application for cell replacement therapy. Exp Neurol. 260: 12-18, 2014 Oct. (4.617)

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