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Peripheral blood-derived mononuclear cells preconditioned by oxygen-glucose deprivation promote functional recovery in ischemic stroke

Research Project

Project/Area Number 18K07493
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52020:Neurology-related
Research InstitutionNiigata University

Principal Investigator

Kanazawa Masato  新潟大学, 脳研究所, 准教授 (80645101)

Co-Investigator(Kenkyū-buntansha) 下畑 享良  岐阜大学, 大学院医学系研究科, 教授 (60361911)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords末梢血単核球 / 細胞療法 / 極性変換 / 血管新生 / 神経軸索進展 / 脳梗塞 / 機能回復 / 脳血管障害 / 極性化 / 脳虚血 / 血管内皮増殖因子 / 保護療法 / 低酸素低糖刺激
Outline of Final Research Achievements

When exogenous peripheral blood mononuclear cells preconditioned by oxygen glucose-deprivation (OGD) were administered to rats with post-ischemic sequelae, angiogenesis and neuronal axonal outgrowth were confirmed, and motor-sensory functions were significantly improved 21 days after cell administration (28 days after ischemia).
We developed a bag that can perform OGD stimulation in a closed system for clinical application, and verified the effect of OGD stimulation on human-derived cells. We also confirmed that the number of SSEA3-positive mononuclear cells, a pluripotent stem cell marker, increased after stimulation. We also showed that cells stimulated with this bag also showed therapeutic effects, and we have applied for a patent.

Academic Significance and Societal Importance of the Research Achievements

本研究により,脳梗塞後の血管新生,組織修復の機序が明らかとなり,慢性期の脳梗塞治療への応用が検討できる.
末梢血を用いることから,細胞確保が容易で,一般病院にも普及する技術になる.さらに発展させることで,脳梗塞患者の機能回復と予後改善が期待され国民医療費の軽減にもつながる.

Report

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

    (31 results)

All 2022 2021 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (11 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 11 results,  Open Access: 4 results) Presentation (10 results) (of which Int'l Joint Research: 8 results,  Invited: 2 results) Book (3 results) Remarks (1 results) Patent(Industrial Property Rights) (5 results) (of which Overseas: 2 results)

  • [Int'l Joint Research] University of Washington(米国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Angiogenesis and neuronal remodeling after ischemic stroke2021

    • Author(s)
      Hatakeyama Masahiro、Ninomiya Itaru、Kanazawa Masato
    • Journal Title

      Neural Regeneration Research

      Volume: 15 Issue: 1 Pages: 16-19

    • DOI

      10.4103/1673-5374.264442

    • Related Report
      2021 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 総説 脳梗塞に対する低酸素低糖刺激末梢血単核球療法2020

    • Author(s)
      畠山公大,二宮至,小野寺理,下畑享良,金澤雅人
    • Journal Title

      BRAIN and NERVE

      Volume: 72 Issue: 10 Pages: 1097-1103

    • DOI

      10.11477/mf.1416201655

    • ISSN
      1344-8129, 1881-6096
    • Year and Date
      2020-10-01
    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cell Therapies under Clinical Trials and Polarized Cell Therapies in Pre-Clinical Studies to Treat Ischemic Stroke and Neurological Diseases: A Literature Review.2020

    • Author(s)
      Hatakeyama M, Ninomiya I, Otsu Y, Omae K, Kimura Y, Onodera O, Fukushima M, Shimohata T, Kanazawa M.
    • Journal Title

      Int J Mol Sci.

      Volume: 21 Issue: 17 Pages: 6194-6194

    • DOI

      10.3390/ijms21176194

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Strategies to prevent hemorrhagic transformation after reperfusion therapies for acute ischemic stroke: A literature review.2020

    • Author(s)
      Otsu Y, Namekawa M, Toriyabe M, Ninomiya I, Hatakeyama M, Uemura M, Onodera O, Shimohata T, Kanazawa M.
    • Journal Title

      J Neurol Sci.

      Volume: 419 Pages: 117217-117217

    • DOI

      10.1016/j.jns.2020.117217

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] HTRA1-Related Cerebral Small Vessel Disease: A Review of the Literature2020

    • Author(s)
      Uemura Masahiro、Nozaki Hiroaki、Kato Taisuke、Koyama Akihide、Sakai Naoko、Ando Shoichiro、Kanazawa Masato、Hishikawa Nozomi、Nishimoto Yoshinori、Polavarapu Kiran、Nalini Atchayaram、Hanazono Akira、Kuzume Daisuke、Shindo Akihiro、El-Ghanem M、Abe A、Sato A、Yoshida M、Ikeuchi T、Mizuta I、Mizuno T、Onodera O
    • Journal Title

      Frontiers in Neurology

      Volume: 11 Pages: 545-545

    • DOI

      10.3389/fneur.2020.00545

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Elevated serum pentraxin 3 levels might predict the diagnosis of branch atheromatous disease at a very early stage2020

    • Author(s)
      Ninomiya I.、Kanazawa M.、Uemura M.、Onodera O.
    • Journal Title

      European Journal of Neurology

      Volume: 27 Issue: 7 Pages: 1279-1284

    • DOI

      10.1111/ene.14249

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Role of RNF213 p.4810K variant in the development of intracranial arterial disease in patients treated with nilotinib2020

    • Author(s)
      Uemura Masahiro、Kanazawa Masato、Yamagishi Takuma、Nagai Takahiro、Takahashi Mami、Koide Shingo、Tada Masayoshi、Shimbo Junsuke、Isami Aiko、Makino Kunihiko、Masuko Masayoshi、Nikkuni Kouji、Okamoto Kouichirou、Igarashi Shuichi、Morita Kenichi、Onodera Osamu
    • Journal Title

      Journal of the Neurological Sciences

      Volume: 408 Pages: 116577-116577

    • DOI

      10.1016/j.jns.2019.116577

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Angiogenesis in the ischemic core: A potential treatment target?2019

    • Author(s)
      Kanazawa M, Takahashi T, Ishikawa M, Onodera O, Shimohata T, Del Zoppo GJ.
    • Journal Title

      J Cereb Blood Flow Metab.

      Volume: Mar 6 Issue: 5 Pages: 753-769

    • DOI

      10.1177/0271678x19834158

    • Related Report
      2021 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A novel therapeutic approach using peripheral blood mononuclear cells preconditioned by oxygen-glucose deprivation.2019

    • Author(s)
      Hatakeyama M, Kanazawa M, Ninomiya I, Omae K, Kimura Y, Takahashi T, Onodera O, Fukushima M, Shimohata T.
    • Journal Title

      Sci Rep.

      Volume: 9 Issue: 1 Pages: 16819-16819

    • DOI

      10.1038/s41598-019-53418-5

    • Related Report
      2021 Annual Research Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] VEGF—A therapeutic target against hemorrhagic transformation after t-PA treatment—2019

    • Author(s)
      Kanazawa Masato、Takahashi Tetsuya、Kawamura Kunio、Shimohata Takayoshi
    • Journal Title

      Rinsho Shinkeigaku

      Volume: 59 Issue: 11 Pages: 699-706

    • DOI

      10.5692/clinicalneurol.cn-001346

    • NAID

      130007742557

    • ISSN
      0009-918X, 1882-0654
    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] HTRA1 Mutations Identified in Symptomatic Carriers Have the Property of Interfering the Trimer-Dependent Activation Cascade2019

    • Author(s)
      Uemura Masahiro、Nozaki Hiroaki、Koyama Akihide、Sakai Naoko、Ando Shoichiro、Kanazawa Masato、Kato Taisuke、Onodera Osamu
    • Journal Title

      Frontiers in Neurology

      Volume: 10 Pages: 693-693

    • DOI

      10.3389/fneur.2019.00693

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Microglia, monocyte, and PBMC polarization reveal therapeutic mechanisms against ischemic stroke2021

    • Author(s)
      Kanazawa Masato
    • Organizer
      第62回日本神経学会学術大会
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A therapeutic approach using peripheral blood mononuclear cells preconditioned by oxygen-glucose deprivation in ischemic rats2021

    • Author(s)
      Kanazawa M, Hatakeyama M, Ninomiya I, Omae K, Kimura Y, Takahashi T, Onodera O, Fukushima M, Shimohata T
    • Organizer
      The Annual Meeting of American Academy of Neurology
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A therapeutic approach using peripheral blood mononuclear cells preconditioned by oxygen-glucose deprivation in ischemic rats2021

    • Author(s)
      78Hatakeyama M, Kanazawa M, Ninomiya I, Omae K, Kimura Y, Takahashi T, Onodera O, Fukushima M, Shimohata T
    • Organizer
      The International Stroke Conference 2020
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A therapeutic approach using peripheral blood mononuclear cells preconditioned by oxygen-glucose deprivation in ischemic rats2020

    • Author(s)
      Hatakeyama Masahiro、Kanazawa Masato、Ninomiya Itaru、Omae Kaoru、Kimura Yasuko、Takahashi Tetsuya、Onodera Osamu、Fukushima Masanori、Shimohata Takayoshi
    • Organizer
      神経学会学術大会
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] ラクナ梗塞とBranch atheromatous diseaseの鑑別における、入院時血清PTX3値の有用性の検討2020

    • Author(s)
      二宮格、金澤雅人、上村昌寛、小野寺理
    • Organizer
      日本脳循環代謝学会
    • Related Report
      2020 Research-status Report
  • [Presentation] A therapeutic approach using peripheral blood mononuclear cells preconditioned by oxygen-glucose deprivation in ischemic rats2020

    • Author(s)
      Hatakeyama Masahiro、Kanazawa Masato、Ninomiya Itaru、Omae Kaoru、Kimura Yasuko、Takahashi Tetsuya、Onodera Osamu、Fukushima Masanori、Shimohata Takayoshi
    • Organizer
      International Stroke Conference 2020
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] A therapy using peripheral blood cells preconditioned by oxygen-glucose deprivation against ischemia2020

    • Author(s)
      Hatakeyama Masahiro、Kanazawa Masato、Ninomiya Itaru、Omae Kaoru、Kimura Yasuko、Takahashi Tetsuya、Onodera Osamu、Fukushima Masanori、Shimohata Takayoshi
    • Organizer
      日本神経学会学術大会
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] ラクナ梗塞とBranch atheromatous diseaseの鑑別における、入院時血清PTX3値の有用性の検討2020

    • Author(s)
      二宮格、金澤雅人、上村昌寛、下畑享良、小野寺理
    • Organizer
      日本脳卒中学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Branch Atheromatous Diseaseにおける急性期の血清Lox-1値の検討2019

    • Author(s)
      二宮格、金澤雅人、赤岩靖久、下畑享良、小野寺理
    • Organizer
      日本神経学会学術大会
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] VEGF ~A therapeutic target against hemorrhagic transformation after t-PA treatment~2018

    • Author(s)
      Masato Kanazawa, Tetsuya Takahashi, Takayoshi Shimohata
    • Organizer
      日本神経学会学術大会
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Book] 最新主要文献とガイドラインでみる 脳神経内科学レビュー 2022-’232022

    • Author(s)
      金澤雅人、鈴木則宏
    • Publisher
      総合医学社
    • ISBN
      9784883784646
    • Related Report
      2021 Annual Research Report
  • [Book] モデル動物の作製と利用-循環器疾患2021 <下巻>2021

    • Author(s)
      大津裕、金澤雅人
    • Publisher
      エル・アイ・シー
    • ISBN
      9784900487598
    • Related Report
      2021 Annual Research Report
  • [Book] Progranulin and Central Nervous System Disorders2021

    • Author(s)
      Kanazawa M, Kawamura K, Takahashi T, Shimohata T
    • Publisher
      Springer Singapore
    • ISBN
      9789811361869
    • Related Report
      2021 Annual Research Report 2018 Research-status Report
  • [Remarks]

    • URL

      https://www.neurology-bri.jp/study/stroke/

    • Related Report
      2021 Annual Research Report
  • [Patent(Industrial Property Rights)] 94OGD(低酸素,低糖刺激)バッグに関する特許2022

    • Inventor(s)
      金澤雅人、畠山公大、下畑享良、井川博史、尾前薫
    • Industrial Property Rights Holder
      金澤雅人、畠山公大、下畑享良、井川博史、尾前薫
    • Industrial Property Rights Type
      特許
    • Filing Date
      2022
    • Related Report
      2021 Annual Research Report
  • [Patent(Industrial Property Rights)] 細胞製剤および細胞製剤の製造方法2022

    • Inventor(s)
      金澤雅人, 下畑享良
    • Industrial Property Rights Holder
      新潟大学
    • Industrial Property Rights Type
      特許
    • Acquisition Date
      2022
    • Related Report
      Products Report
  • [Patent(Industrial Property Rights)] Cell preparation and method for producing cell preparation2022

    • Inventor(s)
      金澤雅人, 下畑享良
    • Industrial Property Rights Holder
      Niigata University
    • Industrial Property Rights Type
      特許
    • Acquisition Date
      2022
    • Related Report
      Products Report
    • Overseas
  • [Patent(Industrial Property Rights)] 細胞製剤の製造方法及びこれに用いる低酸素刺激用容器2021

    • Inventor(s)
      金澤雅人、畠山公大、下畑享良、尾前薫、井川博史
    • Industrial Property Rights Holder
      金澤雅人、畠山公大、下畑享良、尾前薫、井川博史
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2020 Research-status Report
  • [Patent(Industrial Property Rights)] 細胞製剤および細胞製剤の製造方法2018

    • Inventor(s)
      金澤雅人,下畑享良
    • Industrial Property Rights Holder
      金澤雅人,下畑享良
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Research-status Report
    • Overseas

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Published: 2018-04-23   Modified: 2024-03-28  

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