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Development of cell therapy for severe CNS disease using cranial bone mesenchymal stem cells

Research Project

Project/Area Number 18K16561
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56010:Neurosurgery-related
Research InstitutionHiroshima University

Principal Investigator

Mitsuhara Takafumi  広島大学, 医系科学研究科(医), 助教 (80571801)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords神経再生 / 間葉系幹細胞 / 脳梗塞 / 脊髄損傷 / パラクライン効果 / 頭蓋骨由来間葉系幹細胞 / 頭蓋骨 / 移植 / 無血清 / 頭蓋骨間葉系幹細胞 / 微小重力
Outline of Final Research Achievements

We have established cranial bone-derived mesenchymal stem cells (CMSC) originate from neural crest. We have provided novel evidence showing that cell-based therapy using CMSC results in excellent functional recovery in cerebral infarction and spinal cord injury rat models. We have also shown that CMSC exert paracrine effects such as anti-apoptotic and anti-necroptotic effects, suggesting that CMSC may be a new therapeutic agent in cell-based therapy for CNS disease.

Academic Significance and Societal Importance of the Research Achievements

神経再生細胞療法の最適な細胞ソースの候補として、これまで我々は頭蓋骨由来間葉系幹細胞を樹立した.本研究では、頭蓋骨由来間葉系幹細胞の分子生物学的特徴を解析し,実際の神経再生治療への応用を見据えて脳梗塞及び脊髄損傷モデルラットを用いた研究を行い、優れた特性・効果を立証した.本研究を通し,頭蓋骨由来間葉系幹細胞を応用して今後期待される神経再生医療の細胞療法について、多面的な重要知見を得ることができた。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (44 results)

All 2022 2021 2020 2019 2018 Other

All Journal Article (25 results) (of which Peer Reviewed: 20 results,  Open Access: 3 results) Presentation (14 results) (of which Int'l Joint Research: 3 results) Book (3 results) Remarks (2 results)

  • [Journal Article] Transplantation of rat cranial bone-derived mesenchymal stem cells promotes functional recovery in rats with spinal cord injury2021

    • Author(s)
      Maeda Yuyo、Otsuka Takashi、Takeda Masaaki、Okazaki Takahito、Shimizu Kiyoharu、Kuwabara Masashi、Hosogai Masahiro、Yuge Louis、Mitsuhara Takafumi
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 21907-21907

    • DOI

      10.1038/s41598-021-01490-1

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A novel bone-thinning technique for transcranial stimulation motor-evoked potentials in rats2021

    • Author(s)
      Maeda Yuyo、Otsuka Takashi、Mitsuhara Takafumi、Okazaki Takahito、Yuge Louis、Takeda Masaaki
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 12496-12496

    • DOI

      10.1038/s41598-021-91780-5

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparisons of Neurotrophic Effects of Mesenchymal Stem Cells Derived from Different Tissues on Chronic Spinal Cord Injury Rats2021

    • Author(s)
      Otsuka Takashi、Maeda Yuyo、Kurose Tomoyuki、Nakagawa Kei、Mitsuhara Takafumi、Kawahara Yumi、Yuge Louis
    • Journal Title

      Stem Cells and Development

      Volume: 30 Issue: 17 Pages: 865-875

    • DOI

      10.1089/scd.2021.0070

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 頭蓋骨由来間葉系幹細胞を用いた神経再生医療とロボティクスリハビリテーション2021

    • Author(s)
      大塚貴志、光原崇文、中川慧、栗栖薫、 弓削類
    • Journal Title

      BIO Clinica

      Volume: 36 Pages: 372-376

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Effects of Preservation of the Semispinalis Cervicis Inserted into C2 on Craniocervical Alignment After Laminoplasty2021

    • Author(s)
      Shimizu Kiyoharu、Mitsuhara Takafumi、Takeda Masaaki、Kurisu Kaoru、Yamaguchi Satoshi
    • Journal Title

      World Neurosurgery

      Volume: 146 Pages: e1367-e1376

    • DOI

      10.1016/j.wneu.2020.12.017

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Neurosurgical versus endovascular treatment of spinal dural arteriovenous fistulas: a multicenter study of 195 patients2021

    • Author(s)
      Takai Keisuke、Nishimura Yusuke、Eguchi Kaoru、Takami Toshihiro、Watanabe Yusuke、Nishida Takeo、Hiramatsu Masafumi、Ohtonari Tatsuya、Yamaguchi Satoshi、Mitsuhara Takafumi、Matsui Seishi、Uchikado Hisaaki、Hattori Gohsuke、Yamahata Hitoshi、Taniguchi Makoto
    • Journal Title

      Journal of Neurosurgery: Spine

      Volume: 34 Issue: 3 Pages: 514-521

    • DOI

      10.3171/2020.6.spine20309

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Spinal arteriovenous fistula in the lipoma of the filum terminale: A report of two cases and literature review2021

    • Author(s)
      Shimizu Kiyoharu、Mitsuhara Takafumi、Takeda Masaaki、Yamaguchi Satoshi
    • Journal Title

      Surgical Neurology International

      Volume: 12 Pages: 103-103

    • DOI

      10.25259/sni_80_2021

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Integration of Neuro-regenerative Medicine and Robot Rehabilitation2021

    • Author(s)
      Yuge Louis、Mitsuhara Takafumi、Kurisu Kaoru
    • Journal Title

      Japanese Journal of Neurosurgery

      Volume: 30 Issue: 2 Pages: 128-136

    • DOI

      10.7887/jcns.30.128

    • NAID

      130007990818

    • ISSN
      0917-950X, 2187-3100
    • Related Report
      2020 Research-status Report
  • [Journal Article] 研究者の最新動向 頭蓋骨由来間葉系幹細胞を用いた神経再生細胞治療2020

    • Author(s)
      光原, 崇文 弓削, 類 栗栖, 薫
    • Journal Title

      Precision Medicine

      Volume: 3 Pages: 777-782

    • Related Report
      2020 Research-status Report
  • [Journal Article] Extensive solitary fibrous tumor centered on the temporal bone: A case report2020

    • Author(s)
      Sonoyama Toru、Ishino Takashi、Takumida Masaya、Ueda Tsutomu、Takeno Sachio、Mitsuhara Takafumi
    • Journal Title

      Otolaryngology Case Reports

      Volume: 17 Pages: 100239-100239

    • DOI

      10.1016/j.xocr.2020.100239

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Microsurgical versus endovascular treatment of spinal epidural arteriovenous fistulas with intradural venous drainage: a multicenter study of 81 patients2020

    • Author(s)
      Takai Keisuke、Nishimura Yusuke、Eguchi Kaoru、Takami Toshihiro、Watanabe Yusuke、Nishida Takeo、Hiramatsu Masafumi、Ohtonari Tatsuya、Yamaguchi Satoshi、Mitsuhara Takafumi、Matsui Seishi、Uchikado Hisaaki、Hattori Gohsuke、Horie Nobutaka、Yamahata Hitoshi、Taniguchi Makoto
    • Journal Title

      Journal of Neurosurgery: Spine

      Volume: 33 Issue: 3 Pages: 381-391

    • DOI

      10.3171/2020.2.spine191432

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Early Transplantation of Human Cranial Bone-derived Mesenchymal Stem Cells Enhances Functional Recovery in Ischemic Stroke Model Rats2020

    • Author(s)
      OSHITA Jumpei、OKAZAKI Takahito、MITSUHARA Takafumi、IMURA Takeshi、NAKAGAWA Kei、OTSUKA Takashi、KUROSE Tomoyuki、TAMURA Takayuki、ABIKO Masaru、TAKEDA Masaaki、KAWAHARA Yumi、YUGE Louis、KURISU Kaoru
    • Journal Title

      Neurologia medico-chirurgica

      Volume: 60 Issue: 2 Pages: 83-93

    • DOI

      10.2176/nmc.oa.2019-0186

    • NAID

      130007798580

    • ISSN
      0470-8105, 1349-8029
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transient Cerebral Vasospasm After Carotid Artery Stenting: A Case Report and Literature Review2020

    • Author(s)
      Kuwabara Masashi、Nakahara Toshinori、Mitsuhara Takafumi、Shimonaga Koji、Hosogai Masahiro、Kurisu Kaoru、Sakamoto Shigeyuki
    • Journal Title

      World Neurosurgery

      Volume: 135 Pages: 107-111

    • DOI

      10.1016/j.wneu.2019.11.151

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Asymptomatic spinal dural arteriovenous fistula: case series and systematic review2019

    • Author(s)
      Shimizu Kiyoharu、Takeda Masaaki、Mitsuhara Takafumi、Tanaka Shunichi、Nagano Yushi、Yamahata Hitoshi、Kurisu Kaoru、Yamaguchi Satoshi
    • Journal Title

      Journal of Neurosurgery: Spine

      Volume: 31 Issue: 5 Pages: 733-741

    • DOI

      10.3171/2019.5.spine181513

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cauda Equina Occupation Ratio as a New Imaging Parameter for the Evaluation of Spinal Dural Arteriovenous Fistulae2019

    • Author(s)
      Yamahata Hitoshi、Yamaguchi Satoshi、Osanai Toshiya、Takeda Masaaki、Mitsuhara Takafumi、Mori Masanao、Tanaka Shunichi、Yonenaga Masanori、Taguchi Akira、Watanabe Yosuke、Abiko Masaru、Seki Toshitaka、Sasamori Toru、Arita Kazunori、Yoshimoto Koji
    • Journal Title

      World Neurosurgery

      Volume: 130 Pages: e1020-e1027

    • DOI

      10.1016/j.wneu.2019.07.069

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] 頭蓋骨由来間葉系幹細胞の可能性2019

    • Author(s)
      光原 崇文、猪村剛史、弓削類、栗栖薫
    • Journal Title

      別冊BIO Clinica 慢性炎症と疾患

      Volume: 8 Pages: 114-119

    • Related Report
      2019 Research-status Report
  • [Journal Article] 神経再生医療における頭蓋骨由来間葉系幹細胞を用いた挑戦2019

    • Author(s)
      光原 崇文、猪村剛史、弓削類、栗栖薫
    • Journal Title

      BIO Clinica

      Volume: 34 Pages: 1367-1372

    • Related Report
      2019 Research-status Report
  • [Journal Article] 症例 バセドウ病に合併した類もやもや病術後過灌流症候群の1例2018

    • Author(s)
      下永皓司, 光原崇文, 細貝昌弘, 川住知弘
    • Journal Title

      Neurological Surgery 脳神経外科

      Volume: 46 Issue: 6 Pages: 501-508

    • DOI

      10.11477/mf.1436203759

    • ISSN
      0301-2603, 1882-1251
    • Year and Date
      2018-06-10
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Rat Cranial Bone-Derived Mesenchymal Stem Cell Transplantation Promotes Functional Recovery in Ischemic Stroke Model Rats2018

    • Author(s)
      Abiko, M. Mitsuhara, T. Okazaki, T. Imura, T. Nakagawa, K. Otsuka, T. Oshita, J. Takeda, M. Kawahara, Y. Yuge, L. Kurisu, K.
    • Journal Title

      Stem Cells Dev

      Volume: 27 Issue: 15 Pages: 1053-1061

    • DOI

      10.1089/scd.2018.0022

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ruptured dissecting aneurysms of the A1 segment of the anterior cerebral artery: three case reports and a review of the literature2018

    • Author(s)
      Mitsuhara, T. Ikawa, F. Hidaka, T. Kurokawa, Y. Yonezawa, U.
    • Journal Title

      Neurosurg Rev

      Volume: 41 Issue: 2 Pages: 409-414

    • DOI

      10.1007/s10143-017-0841-0

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Multivariate risk factor analysis and literature review of postoperative deterioration in Karnofsky Performance Scale score in elderly patients with skull base meningioma2018

    • Author(s)
      Kolakshyapati Manish、Ikawa Fusao、Abiko Masaru、Mitsuhara Takafumi、Kinoshita Yasuyuki、Takeda Masaaki、Kurisu Kaoru、_ _
    • Journal Title

      Neurosurgical Focus

      Volume: 44 Issue: 4 Pages: E14-E14

    • DOI

      10.3171/2018.1.focus17730

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Usefulness of Preoperative Simulation in Skull Base Approach: A Case Report2018

    • Author(s)
      Kolakshyapati, M. Ikawa, F. Abiko, M. Mitsuhara, T. Takeda, M. Shrestha, T. Kurisu, K.
    • Journal Title

      J Neurol Surg B Skull Base

      Volume: 79 Issue: S 04 Pages: S378-S382

    • DOI

      10.1055/s-0038-1660843

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Concurrent Schwannoma and Meningioma Arising in the Same Spinal Level: A Report of Two Cases2018

    • Author(s)
      Matsuda, S. Kajihara, Y. Abiko, M. Mitsuhara, T. Takeda, M. Karlowee, V. Yamaguchi, S. Amatya, V. J. Kurisu, K.
    • Journal Title

      NMC Case Report Journal

      Volume: 5 Issue: 4 Pages: 105-109

    • DOI

      10.2176/nmccrj.cr.2017-0207

    • NAID

      130007492484

    • ISSN
      2188-4226
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Epidemiology and Overview of the Clinical Spectrum of Degenerative Cervical Myelopathy2018

    • Author(s)
      Yamaguchi, S. Mitsuhara, T. Abiko, M. Takeda, M. Kurisu, K.
    • Journal Title

      Neurosurg Clin N Am

      Volume: 29 Issue: 1 Pages: 1-12

    • DOI

      10.1016/j.nec.2017.09.001

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Intraoperative Neurophysiologic Monitoring for Degenerative Cervical Myelopathy2018

    • Author(s)
      Takeda, M. Yamaguchi, S. Mitsuhara, T. Abiko, M. Kurisu, K.
    • Journal Title

      Neurosurg Clin N Am

      Volume: 29 Issue: 1 Pages: 159-167

    • DOI

      10.1016/j.nec.2017.09.012

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 模擬微小重力環境で培養したヒト頭蓋骨由来間葉系幹細胞による 脳梗塞モデルラットへの移植効果の検討2022

    • Author(s)
      桑原政志、光原崇文、大塚貴志、岡崎貴仁、武田正明、 清水陽元、細貝昌弘、前田雄洋、河原裕美、堀江信貴、弓削類
    • Organizer
      第21回日本再生医療学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 脊髄損傷モデルラットにおけるMEP測定閾値の同定2022

    • Author(s)
      前田雄洋、武田正明、光原崇文、岡崎貴仁、桑原正志、 細貝昌弘、大塚貴志、河原裕美、弓削類、堀江信貴
    • Organizer
      第21回日本再生医療学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ラットにおける、経時的で安定したMEP測定の新たな手技の確立2021

    • Author(s)
      前田 雄洋, 武田 正明, 大塚 貴志, 桑原 政志, 細貝 昌弘, 清水 陽元, 光原 崇文, 岡崎 貴仁, 弓削 類
    • Organizer
      第80回日本脳神経外科学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] RAT CRANIAL BONE-DERIVED MESENCHYMAL STEM CELL TRANSPLANTATION PROMOTES FUNCTIONAL RECOVERY IN SPINAL CORD INJURY MODEL RATS2021

    • Author(s)
      Yuyo Maeda, Takafumi Mitsuhara, Takashi Otsuka, Masaaki Takeda, Takahito Okazaki, Kiyoharu Shimizu, Masashi Kuwabara, Yumi Kawahara, Koichiro Tsuji, Louis Yuge
    • Organizer
      ISSCR 2021 Annual Meeting
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ラット頭蓋骨由来間葉系幹細胞の脊髄損傷への移植効果2021

    • Author(s)
      前田雄洋、光原崇文、大塚貴志、岡崎貴仁、武田正明、 清水陽元、桑原正志、細貝昌弘、河原裕美、辻 紘一郎、 飯田幸治、弓削類
    • Organizer
      第20回日本再生医療学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] Histological and clinical consideration of the refluxed medullary veins in thoracolumbar spinal dural arteriovenous fistulas2019

    • Author(s)
      Takafumi Mitsuhara, Hitoshi Yamahata, Kiyoharu Shimizu, Masaaki Takeda, Kaoru Kurisu, and Satoshi Yamaguchi
    • Organizer
      The 10th ASIA SPINE
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 経頭蓋での視神経管内鼻内側病変へのアプローチ2019

    • Author(s)
      光原崇文, 木下 康之, 武田 正明, 栗栖 薫
    • Organizer
      第31回日本頭蓋底外科学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 脊髄硬膜動静脈瘻に対する治療成績の検討2019

    • Author(s)
      光原崇文, 山畑仁志, 山口智, 清水陽元, 武田正明, 森正如, 吉本幸司, 栗栖薫
    • Organizer
      第34回日本脊髄外科学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Cone-beam CTが有用であったBow hunter症候群の一例2019

    • Author(s)
      光原崇文、武田正明、荒木勇人、久米伸治、森岡博美、阿美古将、坂本繁幸、栗栖薫
    • Organizer
      STROKE 2019
    • Related Report
      2019 Research-status Report
  • [Presentation] THE NEUROPROTECTIVE AND NEUROREGENERATIVE POTENTIAL OF HUMAN CRANIAL BONE MARROW-DERIVED MESENCHYMAL STEM CELLS2018

    • Author(s)
      Takafumi Mitsuhara, Takeshi Imura, Takashi Ohtsuka, Junpei Ohshita, Masaru Abiko, Kaori Iwamoto, Takahito Okazaki, Yumi Kawahara, Louis Yuge, Kaoru Kurisu
    • Organizer
      International Society for Stem Cell Research (ISSCR) Annual Meeting 2019
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 頭蓋骨由来骨髄間葉系幹細胞の神経再生・保護効果~新しい間葉系幹細胞ソースとして ~2018

    • Author(s)
      光原崇文、猪村剛史, 大塚貴志, 大下純平, 阿美古将, 岩本佳央梨, 岡崎貴仁, 河原裕美, 弓削類, 栗栖薫
    • Organizer
      第77回日本脳神経外科学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 胸腰椎移行部硬膜動静脈瘻における逆流静脈の動脈化2018

    • Author(s)
      光原崇文、山口智、武田正明、阿美古将、田口慧、大庭信二、栗栖薫
    • Organizer
      第33回日本脊髄外科学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 眼窩内原発solitary fibrous tumorの検討2018

    • Author(s)
      光原崇文、武田正明、阿美古将、杉山一彦、栗栖薫
    • Organizer
      第30回日本頭蓋底外科学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 歯突起後方偽腫瘍の 検討2018

    • Author(s)
      光原崇文、武田正明、阿美古将、栗栖 薫
    • Organizer
      第23回関西脳神経外科手術研究会
    • Related Report
      2018 Research-status Report
  • [Book] かんテキ 脳神経2019

    • Author(s)
      光原崇文
    • Total Pages
      432
    • Publisher
      メディカ出版
    • ISBN
      4840469229
    • Related Report
      2019 Research-status Report
  • [Book] 脳腫瘍外科 経験したい手術162019

    • Author(s)
      光原崇文、栗栖薫、井川房夫
    • Total Pages
      364
    • Publisher
      メジカルビュー
    • ISBN
      9784758318501
    • Related Report
      2018 Research-status Report
  • [Book] 再生医療とリハビリテーション2018

    • Author(s)
      光原崇文、栗栖薫
    • Total Pages
      190
    • Publisher
      三輪書店
    • ISBN
      9784895906289
    • Related Report
      2018 Research-status Report
  • [Remarks] 広島大学大学院医系科学研究科脳神経外科学 神経再生研究グループ

    • URL

      https://shinkeisaisei.hiroshima-u.ac.jp/

    • Related Report
      2021 Annual Research Report
  • [Remarks] 広島大学大学院医系科学研究科 脳神経外科学 神経再生研究グループ

    • URL

      https://shinkeisaisei.hiroshima-u.ac.jp/

    • Related Report
      2020 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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