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Umbilical cord blood cell therapies in a novel neonatal stroke model

Research Project

Project/Area Number 24591617
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Embryonic/Neonatal medicine
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

TSUJI MASAHIRO  独立行政法人国立循環器病研究センター, 再生医療部, 室長 (80579467)

Co-Investigator(Kenkyū-buntansha) TAGUCHI Akihiko  先端医療センター, 再生医療研究部, 部長 (10359276)
Co-Investigator(Renkei-kenkyūsha) YAMAHARA Kenichi  国立循環器病研究センター, 研究所, 室長 (50450888)
IIDA Hidehiro  国立循環器病研究センター, 研究所, 部長 (30322720)
ENMI Junichiro  国立循環器病研究センター, 研究所, 研究員 (80393205)
MATSUYAMA Tomohiro  兵庫医科大学, 先端医学研究所 神経再生研究部門, 教授 (10219529)
HAYAKAWA Masahiro  名古屋大学, 医学部 総合周産期母子医療センター新生児部門, 病院教授 (40343206)
SATO Yoshiaki  名古屋大学, 医学部 総合周産期母子医療センター新生児部門, 講師 (30435862)
MISHIMA Kenichi  福岡大学, 薬学部 臨床疾患薬理学, 准教授 (00320309)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords新生児脳梗塞 / 新生児脳症 / 新生児低酸素性虚血性脳症 / 臍帯血 / 幹細胞 / 細胞治療 / マウス / 脳血流 / 臍帯血幹細部 / 中大脳動脈閉塞 / CD34陽性細胞 / 新生児 / 脳障害 / 虚血 / 脳梗塞 / 低酸素性虚血 / 脳傷害
Outline of Final Research Achievements

Currently, the rodent models of neonatal ischemic brain damage that are available exhibit significant inter-animal variability, which makes it difficult to accurately assess the mechanisms of brain injury and the efficacy of candidate treatments. By using specific mouse strain, CB-17, we succeeded in producing a novel, highly reproducible model of neonatal stroke, middle cerebral artery occlusion (MCAO).
We examined the effects of human umbilical cord blood CD34+ cells (hematopoietic stem cell/endothelial progenitor cells) in the mouse model of neonatal stroke. The stem cells were injected intravenously 48 hours after MCAO. With the cell treatment, cerebral blood flow, morphological brain damage, and behavioral alterations were significantly ameliorated compared with the control group.
After preclinical studies including this study, we have started a clinical study “Autologous cord blood cell therapy for neonatal encephalopathy”.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (24 results)

All 2015 2014 2013 2012 Other

All Journal Article (7 results) (of which Peer Reviewed: 6 results,  Acknowledgement Compliant: 1 results) Presentation (16 results) (of which Invited: 1 results) Book (1 results)

  • [Journal Article] ntraperitoneal and intravenous deliveries are not comparable in terms of drug efficacy and cell distribution in neonatal mice with hypoxia-ischemia2015

    • Author(s)
      Ohshima M, Taguchi A, Tsuda H, Sato Y, Yamahara K, Harada-Shiba M, Miyazato M, Ikeda T, Iida H, Tsuji M
    • Journal Title

      Brain Dev

      Volume: 37 Issue: 4 Pages: 376-386

    • DOI

      10.1016/j.braindev.2014.06.010

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Effects of intravenous administration of umbilical cord blood CD34+ cells in a mouse model of neonatal stroke.2014

    • Author(s)
      Tsuji M, Taguchi A, Ohshima M, Kasahara Y, Sato Y, Tsuda H, Otani K, Yamahara K, Ihara M, Harada-Shiba M, Ikeda T, Matsuyama T.
    • Journal Title

      Neuroscience

      Volume: 263 Pages: 148-158

    • DOI

      10.1016/j.neuroscience.2014.01.018

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] A novel reproducible model of neonatal stroke in mice: comparison with a hypoxia-ischemia model.2013

    • Author(s)
      Tsuiji et al., 他11名
    • Journal Title

      Exp Neurol.

      Volume: 247 Pages: 218-225

    • DOI

      10.1016/j.expneurol.2013.04.015

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Progesterone and allopregnanolone exacerbate hypoxic-ischemic brain injury in immature rats.2012

    • Author(s)
      Masahiro Tsuji, Akihiko Taguchi, Makiko Ohshima, Yukiko Kasahara, Tomoaki Ikeda.
    • Journal Title

      Experimental Neurology

      Volume: 233 Issue: 1 Pages: 214-220

    • DOI

      10.1016/j.expneurol.2011.10.004

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cerebral blood flow during reperfusion predicts later brain damage in a mouse and a rat model of neonatal hypoxic-ischemic encephalopathy.2012

    • Author(s)
      Makiko Ohshima, Masahiro Tsuji, Akihiko Taguchi, Yukiko Kasahara, Tomoaki Ikeda.
    • Journal Title

      Experimental Neurology

      Volume: 233 Issue: 1 Pages: 481-489

    • DOI

      10.1016/j.expneurol.2011.11.025

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 再生医療の現状と将来:脳血管障害患者に対する細胞治療とその将来2012

    • Author(s)
      辻 雅弘、笠原由紀子、田口 明彦
    • Journal Title

      日本老年医学会雑誌

      Volume: 49 Pages: 528-533

    • Related Report
      2012 Research-status Report
  • [Journal Article] 細菌性髄膜炎における頭部造影 MRI の検討―治療期間判定での臨床的意義2012

    • Author(s)
      原田明佳、辻雅弘、吉田健司
    • Journal Title

      脳と発達

      Volume: 44 Pages: 315-319

    • NAID

      10030802003

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 新生児低酸素性虚血性脳症に対する自己臍帯血幹細胞治療の臨床試験開始2015

    • Author(s)
      辻 雅弘、鍋谷まこと、市場博幸、岡 明、佐藤義朗、田村正徳、濱崎考史、早川昌弘、渡部 晋一、新宅治夫
    • Organizer
      第118回日本小児科学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2015-04-17 – 2015-04-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] Intravenous administration of umbilical cord blood CD34+ cells ameliorates brain injury in a mouse model of neonatal stroke2015

    • Author(s)
      Tsuji M, Taguchi A, Ohshima M, Kasahara Y, Sato Y, Otani K, Yamahara K, Ihara M, Harada-Shiba M, Ikeda T, Matsuyama T
    • Organizer
      The 11th Asian Society for Pediatric Research
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      2015-04-15 – 2015-04-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 幹細胞療法の臨床応用へのみちのり シンポジウム2「HIEのこれからの治療」2014

    • Author(s)
      辻 雅弘
    • Organizer
      第59回日本未熟児新生児学会学術集会
    • Place of Presentation
      松山
    • Year and Date
      2014-11-10 – 2014-11-12
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] MRI/PETイメージングによる低酸素性虚血性脳症の脳循環動態と遠隔期脳障害との関連:ラットモデルでの検討2014

    • Author(s)
      辻 雅弘
    • Organizer
      第59回日本未熟児新生児学会学術集会
    • Place of Presentation
      松山
    • Year and Date
      2014-11-10 – 2014-11-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] ハイブリッドMR/PETイメージングによる小児低酸素性虚血性脳症ラットモデルの経時的解析2014

    • Author(s)
      辻 雅弘、圓見純一郎、森口哲朗、越野一博、大嶌麻妃子、飯田秀博
    • Organizer
      第37回日本神経科学大会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] MRI/PETイメージングによる低酸素性虚血性脳症の脳循環動態評価:ラットモデルでの検討2014

    • Author(s)
      辻 雅弘、圓見純一郎、飯田秀博
    • Organizer
      第50回日本周産期・新生児医学会学術集会
    • Place of Presentation
      浦安
    • Year and Date
      2014-07-13 – 2014-07-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] A reproducible model of neonatal stroke in mice: comparison with a hypoxia-ischemia model2014

    • Author(s)
      Tsuji M, Ohshima M, Taguchi A, Kasahara Y, Ikeda T, Matsuyama T
    • Organizer
      The 9th Hershey Conference on Developmental Brain Injury
    • Place of Presentation
      St. Michaels, Maryland, USA
    • Year and Date
      2014-06-03 – 2014-06-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] 幹細胞静脈内投与後の体内分布;新生児低酸素性虚血性脳症マウスと脳梗塞カニクイザルモデルでの検討2014

    • Author(s)
      辻 雅弘
    • Organizer
      第56回日本小児神経学会・学術集会
    • Place of Presentation
      浜松
    • Year and Date
      2014-05-29 – 2014-05-31
    • Related Report
      2014 Annual Research Report
  • [Presentation] Intravenous administration of human CD34+ cord blood cells after neonatal stroke ameliorates brain damage in a mouse model.2012

    • Author(s)
      Masahiro Tsuji, Akihiko Taguchi, Yukiko Kasahara, Makiko Ohshima, Kenichi Yamahara, Tomohiro Matsuyama, Tomoaki Ikeda.
    • Organizer
      The 8th Hershey Conference on Developmental Brain Injury
    • Place of Presentation
      London
    • Related Report
      2012 Research-status Report
  • [Presentation] 新生児脳梗塞モデルマウスに対するヒト臍帯血CD34陽性細胞静脈内投与の効果.2012

    • Author(s)
      辻 雅弘, 田口明彦, 笠原由紀子, 大嶌麻妃子, 山原研一, 池田智明, 松山知弘.
    • Organizer
      第11回日本再生医療学会総会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] 低酸素性虚血性脳症と脳血流:新生仔マウス・ラットでの検討.2012

    • Author(s)
      辻 雅弘
    • Organizer
      第54回日本小児神経学会総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] A novel reproducible model of neonatal stroke in mice: comparison with a hypoxia-ischemia model

    • Author(s)
      Masahiro Tsuji, Makiko Ohshima, Akihiko Taguchi, Yukiko Kasahara, Tomoaki Ikeda, Tomohiro Matsuyama
    • Organizer
      Annual Meeting of Society for Neuroscience 2013
    • Place of Presentation
      San Diego, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] 新生児虚血性脳障害モデルマウスにおける臍帯血CD34陽性細胞移植の効果;第二報

    • Author(s)
      辻 雅弘、大嶌麻妃子
    • Organizer
      第116回日本小児科学会学術集会
    • Place of Presentation
      広島
    • Related Report
      2013 Research-status Report
  • [Presentation] 再現性の高い新生児脳虚血モデルマウスの新規作成:従来の低酸素性虚血性脳症モデルとの比較 –第二報-

    • Author(s)
      辻 雅弘
    • Organizer
      第55回日本小児神経学会・学術集会
    • Place of Presentation
      大分
    • Related Report
      2013 Research-status Report
  • [Presentation] 新生仔マウスでの薬剤・細胞治療において投与経路の違いが及ぼす効果の検討;腹腔内投与と静脈内投与の比較

    • Author(s)
      辻 雅弘、池田智明
    • Organizer
      第49回日本周産期・新生児医学会学術集会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] 幹細胞治療において投与経路・細胞の違いがもたらす体内細胞分布の差;新生児低酸素性虚血性脳症マウスモデルでの検討

    • Author(s)
      辻 雅弘
    • Organizer
      第58回日本未熟児新生児学会・学術集会
    • Place of Presentation
      金沢
    • Related Report
      2013 Research-status Report
  • [Book] Cell-based therapies in neonatal stroke. In: Cell Therapy for Brain Injury2015

    • Author(s)
      Tsuji M, Johnston MV
    • Publisher
      Springer International Publishing
    • Related Report
      2014 Annual Research Report

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

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