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Comprehensive Bench-to-Bedside Research on Regenerative Medicine for Ischemic stroke with Bone Marrow Stromal Cell-derived Extracellular Vesicles (EVs)

Research Project

Project/Area Number 21H03043
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 56010:Neurosurgery-related
Research InstitutionUniversity of Toyama

Principal Investigator

KURODA Satoshi  富山大学, 学術研究部医学系, 教授 (10301904)

Co-Investigator(Kenkyū-buntansha) 柏崎 大奈  富山大学, 学術研究部医学系, 講師 (50374484)
川堀 真人  北海道大学, 大学病院, 特任准教授 (50399870)
堀 恵美子  富山大学, 学術研究部医学系, 講師 (90372482)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2023: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2022: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2021: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Keywords再生医療 / 細胞治療 / Muse細胞 / 脳梗塞 / 脳挫傷 / アルツハイマー病 / 運動機能 / 認知機能 / 骨髄間質細胞 / 細胞外小胞 / 幹細胞
Outline of Research at the Start

本研究は、ヒト他家BMSCから放出された細胞外小胞(EV)を用いた脳梗塞に対する再生医療の第一ステップとしての非臨床試験を主眼とし、ヒトBMSCから放出されたEVを単離してその生物学的特性を検証するとともに、低酸素に暴露された培養神経細胞に投与することで神経細胞に対する保護作用の有無を多角的に検証を行う。
また、ラット脳梗塞モデルに投与することで、至適な投与タイミング、投与EV数、投与経路を探ることで脳梗塞に対する新しい再生治療のドナーとなり得るかどうかを多角的に検証を行う研究である。

Outline of Final Research Achievements

Pluripotent stem cells (Muse cells) isolated from bone marrow stromal cells were transplanted into three animal models of brain diseases via multiple routes, and their therapeutic effects were examined from various angles. (1) Cerebral infarction model: Muse cells were transplanted transvenously or intranasally, and the recovery of motor function was significantly enhanced. (2) Cerebral contusion model: Muse cells were transplanted intravenously, and the recovery of motor function was significantly enhanced. (3) Alzheimer's disease model: Transplantation of Muse cells intranasally significantly suppressed the deterioration of cognitive function. Based on these findings, we plan to expand the study to experiments using EVs derived from Muse cells.

Academic Significance and Societal Importance of the Research Achievements

本研究によって人生100年時代、健康寿命延伸時代においても患者QOLに大きく影響を及ぼす脳梗塞、脳挫傷、アルツハイマー病に対して、従来の薬物療法、リハビリテーションなどの治療よりも治療効果の高い細胞療法の開発に目処がついた。しかも本研究では、細胞の静注のみならず経鼻移植という非侵襲的な移植ルートの効果を示した点で、患者負担の軽い再生療法として画期的な成果が得られた。今後はMuse cellから分離できるEVsの研究を展開するとともに、細胞そのものを用いた臨床研究に発展させる予定である。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (13 results)

All 2024 2023 2022 2021

All Journal Article (12 results) (of which Peer Reviewed: 12 results,  Open Access: 8 results) Book (1 results)

  • [Journal Article] Intracerebral transplantation of MRI-trackable autologous bone marrow stromal cells for patients with subacute ischemic stroke2024

    • Author(s)
      Kawabori Masahito、Kuroda Satoshi、Shichinohe Hideo、Kahata Kaoru、Shiratori Souichi、Ikeda Satoshi、Harada Taisuke、Hirata Kenji、Tha Khin Khin、Aragaki Masato、Terasaka Shunsuke、Ito Yoichi M.、Nishimoto Naoki、Ohnishi Shunsuke、Yabe Ichiro、Kudo Kohsuke、Houkin Kiyohiro、Fujimura Miki
    • Journal Title

      Med

      Volume: - Issue: 5 Pages: 432-444.e4

    • DOI

      10.1016/j.medj.2024.02.009

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Five-Year Stroke Risk and Its Predictors in Asymptomatic Moyamoya Disease: Asymptomatic Moyamoya Registry (AMORE)2023

    • Author(s)
      Kuroda Satoshi、Yamamoto Shusuke、Funaki Takeshi、Fujimura Miki、Kataoka Hiroharu、Hishikawa Tomohito、Takahashi Jun、Endo Hidenori、Nariai Tadashi、Osato Toshiaki、Saito Nobuhito、Sato Norihiro、Hori Emiko、Ito Yoichi M.、Miyamoto Susumu、 AMORE Study Group
    • Journal Title

      Stroke

      Volume: 54 Issue: 6 Pages: 1494-1504

    • DOI

      10.1161/strokeaha.122.041932

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis on the cerebrospinal fluid gas tensions and pH in hemodynamically compromised patients2023

    • Author(s)
      Kuroda Satoshi、Yamamoto Shusuke、Hori Emiko、Kashiwazaki Daina、Noguchi Kyo
    • Journal Title

      Acta Neurochirurgica

      Volume: 165 Issue: 12 Pages: 3709-3715

    • DOI

      10.1007/s00701-023-05855-5

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Diagnostic Criteria for Moyamoya Disease - 2021 Revised Version2022

    • Author(s)
      KURODA Satoshi、FUJIMURA Miki、TAKAHASHI Jun、KATAOKA Hiroharu、OGASAWARA Kuniaki、IWAMA Toru、TOMINAGA Teiji、MIYAMOTO Susumu、The Research Committee on Moyamoya Disease (Spontaneous Occlusion of Circle of Willis) of the Ministry of Health, Labor, and Welfare, Japan
    • Journal Title

      Neurologia medico-chirurgica

      Volume: 62 Issue: 7 Pages: 307-312

    • DOI

      10.2176/jns-nmc.2022-0072

    • ISSN
      0470-8105, 1349-8029
    • Year and Date
      2022-07-15
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 特集 STA-MCAバイパス術-日本が世界に誇る技を学ぶ Ⅲ特殊なバイパス術 もやもや病に対するバイパス術Ⅰ:その特殊性,成人例に対する私の手術法2022

    • Author(s)
      黒田 敏
    • Journal Title

      Neurological Surgery 脳神経外科

      Volume: 50 Issue: 4 Pages: 806-818

    • DOI

      10.11477/mf.1436204624

    • ISSN
      0301-2603, 1882-1251
    • Year and Date
      2022-07-10
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 特集 こんなときどうする?他科とのコミュニケーションガイド (第6章)脳神経内科・脳神経外科 妊産婦脳卒中2022

    • Author(s)
      黒田 敏
    • Journal Title

      産科と婦人科

      Volume: 89 Issue: 13 Pages: 268-273

    • DOI

      10.34433/J00525.2022140465

    • ISSN
      0386-9792
    • Year and Date
      2022-03-25
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Thin calcification (<2 mm) can highly predict intraplaque hemorrhage in carotid plaque: the clinical significance of calcification types.2022

    • Author(s)
      Kashiwazaki D, Yamamoto S, Hori E, Akioka N, Noguchi K, Kuroda S.
    • Journal Title

      Acta Neurochirurgica

      Volume: Apr 12 Issue: 6 Pages: 1635-1643

    • DOI

      10.1007/s00701-022-05205-x

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differentiation of Fibroblasts Into Myofibroblasts in the Arachnoid Membrane of Moyamoya Disease.2022

    • Author(s)
      Yamamoto S, Yamamoto S, Akai T, Sasahara M, Kuroda S.
    • Journal Title

      Stroke

      Volume: 53 Issue: 11 Pages: 3465-73

    • DOI

      10.1161/strokeaha.122.039961

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] くも膜下出血2022

    • Author(s)
      黒田 敏
    • Journal Title

      今日の治療指針2022

      Volume: - Pages: 943-945

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 脳卒中治療ガイドライン20212022

    • Author(s)
      黒田 敏、遠藤 薫、板橋 亮、小笠原邦昭、宮本 享
    • Journal Title

      日本臨床

      Volume: 80 Suppl 1 Pages: 34-38

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Potential of Combination of Bone Marrow Nucleated and Mesenchymal Stem Cells in Complete Spinal Cord Injury2021

    • Author(s)
      Katoh Shojiro、Dedeepiya Vidyasagar D.、Kuroda Satoshi、Iwasaki Masaru、Senthilkumar Rajappa、Preethy Senthilkumar、Abraham Samuel J.K.
    • Journal Title

      Current Stem Cell Research &amp; Therapy

      Volume: 16 Issue: 4 Pages: 385-399

    • DOI

      10.2174/1574888x15666201029160542

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cerebrospinal fluid may flow out from the brain through the frontal skull base and choroid plexus: a gold colloid and cadaverine injection study in mouse fetus2021

    • Author(s)
      Akai Takuya、Hatta Toshihisa、Sakata-Haga Hiromi、Yamamoto Seiji、Otani Hiroki、Yamamoto Shusuke、Kuroda Satoshi
    • Journal Title

      Child's Nervous System

      Volume: 37 Issue: 10 Pages: 3013-3020

    • DOI

      10.1007/s00381-021-05253-1

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Book] 脳卒中エキスパート 神経保護・神経再生療法~今後の展望と課題2021

    • Author(s)
      鈴木則宏 シリーズ監修 / 黒田 敏 編集
    • Total Pages
      210
    • Publisher
      中外医学社
    • Related Report
      2021 Annual Research Report

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

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