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Optimization of the host brain environment for the cell replacement therapy using ES cells

Research Project

Project/Area Number 20390383
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionKyoto University

Principal Investigator

TAKAHASHI Jun  Kyoto University, 再生医科学研究所, 准教授 (10270779)

Co-Investigator(Kenkyū-buntansha) HASHIMOTO Nobuo  京都大学, 大学院・医学研究科, 教授 (40135570)
TAKAHASHI Ryosuke  京都大学, 大学院・医学研究科, 教授 (90216771)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
Fiscal Year 2010: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2009: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2008: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Keywords実験脳外科学 / ES細胞 / 神経分化 / 細胞移植 / 炎症
Research Abstract

The final goal of this study was to optimize the host brain environment for the cell replacement therapy using ES cells. By this study, we have obtained the following results : 1) Single and local blockade of IL-6 signaling promoted neuronal differentiation of transplanted ES cell-derived neural precursor cells. 2) Systemic administration of CTLA4-Ig promoted neuronal differentiation of transplanted ES cell-derived neural precursor cells. 3) Nonhypotensive dose of Telmisartan attenuated cognitive impariment partially due to peroxisome proliferator-activated receptor-γ activation in mice with chronic cerebral hypoperfusion.
These results suggest that the host brain environment plays an important role in a transplantation of ES cell-derived neural cells, and also that we need to control the inflammation in the host brain for the efficient transplantation.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (42 results)

All 2011 2010 2009 2008 Other

All Journal Article (8 results) (of which Peer Reviewed: 6 results) Presentation (33 results) Remarks (1 results)

  • [Journal Article] Single and local blockade of IL-6 signaling promotes neuronal differentiation of transplanted ES cell-derived neural precursor cells.2011

    • Author(s)
      Gomi M, Aoki T, Takagi Y, Nishimura M, Ohsugi Y, Mihara M, Nozaki K, Hashimoto N, Miyamoto S, Takahashi J.
    • Journal Title

      J Neurosci Res (in press)

    • Related Report
      2010 Final Research Report
  • [Journal Article] Single and local blockade of IL-6 signaling promotes neuronal differentiation of transplanted ES cell-derived neural precursor cells.2011

    • Author(s)
      Gomi M, Aoki T, Takagi Y, Nishimura M, Ohsugi Y, Mihara M, Nozaki K, Hashimoto N, Miyamoto S, Takahashi J.
    • Journal Title

      J Neurosci Res

      Volume: (in press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nonhypotensive Dose of Telmisartan Attenuates Cognitive Impariment Partially due to Peroxisome Proliferator-Activated Receptor-γ Activation in Mice with Chronic Cerebral Hypoperfusion.2010

    • Author(s)
      Washida K, Ihara M, Nishio K, Fujita Y, Maki T, Yamada M, Takahashi J, Wu X, Kihara T, Ito H, Tomimoto H, Takahashi R.
    • Journal Title

      Stroke. 2010 41

      Pages: 1798-1806

    • Related Report
      2010 Final Research Report
  • [Journal Article] Nonhypotensive dose of Telmisartan attenuates cognitive impairment partially due to peroxisome proliferator-activated receptor-γ activation in mice with chronic cerebral hypoperfusion.2010

    • Author(s)
      Washida K, Ihara M, Nishio K, Fujita Y, Maki T, Yamada M, Takahashi J, Wu X, Kihara T, Ito H, Tomimoto H, Takahashi R.
    • Journal Title

      Stroke

      Volume: 41 Pages: 1798-1806

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Matrigel supports survival and neuronal differentiation of grafted embryonic stem cell-derived neural precursor cells2010

    • Author(s)
      Uemura M, Refaat M.M, Shinoyama M, Hayashi H, Hashimoto N, Takahashi J.
    • Journal Title

      J Neurosci Res 88

      Pages: 542-551

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immune or inflammatory response by the host brain suppresses neuronal differentiation of transplanted ES cell-derived neural precursor cells.2008

    • Author(s)
      Ideguchi M, Shinoyama M, Gomi M, Hayashi H, Hashimoto N, Takahashi J.
    • Journal Title

      J Neurosci Res 86(9)

      Pages: 1936-1943

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Meningeal cells induce dopaminergic neurons from embryonic stem cells.2008

    • Author(s)
      Hayashi H, Morizane A, Koyanagi M, Ono Y, Sasai Y, Hashimoto N, Takahashi J.
    • Journal Title

      Eur J Neurosci 27

      Pages: 261-268

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of the Rho/ROCK pathway reduces apoptosis during transplantation of embryonic stem cell-derived neural precursors.2008

    • Author(s)
      Koyanagi M, Takahashi J, Arakawa Y, Doi D, Fukuda H, Hayashi. H, Narumiya S, Hashimoto N.
    • Journal Title

      J Neurosci Res 86(2)

      Pages: 270-280

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Nonhypotensive Dose of Telmisartan Attenuates Cognitive Impairment Partiyally Due to Peroxisome Proliferator-Activated-γ Activation in Mice With Chronic Cerebral Hypoperfusion.2010

    • Author(s)
      Washida K, Ihara M, Nishio K, Fujita Y, Maki T, Yamada M, Takahashi J, Wu X, Kihara T, Ito H, Tomimoto H, Takahashi R.
    • Organizer
      The 22^<nd> Annual Meeting of the Japanese Society of Cerebral Blood Flow and Metabolism
    • Place of Presentation
      Osaka
    • Year and Date
      2010-11-27
    • Related Report
      2010 Final Research Report
  • [Presentation] Nonhypotensive Dose of Telmisartan Attenuates Cognitive Impairment Partiyally Due to Peroxisome Proliferator-Activated-γ Activation in Mice With Chronic Cerebral Hypoperfusion.2010

    • Author(s)
      Washida K, Ihara M, Nishio K, Fujita Y, Maki T, Yamada M, Takahashi J, Wu X, Kihara T, Ito H, Tomimoto H, Takahashi R.
    • Organizer
      The 2^<nd> Kyoto Neuropathology Conference
    • Place of Presentation
      Kyoto
    • Year and Date
      2010-11-25
    • Related Report
      2010 Final Research Report
  • [Presentation] Nifedipine, a calcium-channel blocker attenuates cognitive impairment and white matter damages in a mice with chronic cerebral hypoperfusion.2010

    • Author(s)
      Washida K, Ihara M, Okamoto Y, Ito H, Tomimoto H, Takahashi R
    • Organizer
      Neuroscience 2010
    • Place of Presentation
      San Diego
    • Year and Date
      2010-11-15
    • Related Report
      2010 Final Research Report
  • [Presentation] Nonhypotensive Dose of Telmisartan Attenuates Cognitive Impairment Partiyally Due to Peroxisome Proliferator-Activated-γ Activation in Mice With Chronic Cerebral Hypoperfusion.2010

    • Author(s)
      Washida K, Ihara M, Nishio K, Fujita Y, Maki T, Yamada M, Takahashi J, Wu X, Kihara T, Ito H, Tomimoto H, Takahashi R.
    • Organizer
      The 33^<rd> Annual Meeting of the Japan Neuroscience Society
    • Place of Presentation
      Kobe
    • Year and Date
      2010-09-19
    • Related Report
      2010 Final Research Report
  • [Presentation] Nonhypotensive Dose of Telmisartan Attenuates Cognitive Impairment Partially Due to Peroxisome Proliferator-Activated-γ Activation in Mice With Chronic Cerebral Hypoperfusion.2010

    • Author(s)
      Washida K, Ihara M, Nishio K, Fujita Y, Maki T, Yamada M, Takahashi J, et al.
    • Organizer
      The 33^<rd> Annual Meeting of the Japan Neuroscience Society
    • Place of Presentation
      神戸
    • Year and Date
      2010-09-19
    • Related Report
      2010 Annual Research Report
  • [Presentation] Nonhypotensive Dose of Telmisartan Attenuates Cognitive Impairment Partiyally Due to Peroxisome Proliferator-Activated-γ Activation in Mice With Chronic Cerebral Hypoperfusion.2010

    • Author(s)
      Washida K, Ihara M, Nishio K, Fujita Y, Maki T, Yamada M, Takahashi J, Wu X, Kihara T, Ito H, Tomimoto H, Takahashi R.
    • Organizer
      The 1st Annual Neuroscience Conference
    • Place of Presentation
      Nairobi, Kenya
    • Year and Date
      2010-09-07
    • Related Report
      2010 Final Research Report
  • [Presentation] パーキンソン病に対する幹細胞移植治療の開発研究2010

    • Author(s)
      高橋淳、五味正憲
    • Organizer
      神経組織の成長・再生・移植研究会第25回学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2010-05-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] Nonhypotensive Dose of Telmisartan Attenuates Cognitive Impariment Partially due to PPAR-γ Activation in Mice with Chronic Cerebral Hypoperfusion.2010

    • Author(s)
      Washida K, Ihara M, Nishio K, Fujita Y, Maki T, Yamada M, Takahashi J, Wu X, Kihara T, Ito H, Tomimoto H, Takahashi R.
    • Organizer
      The 51^<st> Annual Meeting of Japanese Society of Neurology
    • Place of Presentation
      Tokyo
    • Year and Date
      2010-05-20
    • Related Report
      2010 Final Research Report
  • [Presentation] Nonhypotensive Dose of Telmisartan Attenuates Cognitive Impariment Partially due to PPAR-γ Activation in Mice with Chronic Cerebral Hypoperfusion.2010

    • Author(s)
      Washida K, Ihara M, Nishio K, Fujita Y, Maki T, Yamada M, Takahashi J, Wu X, Kihara T, Ito H, Tomimoto H, Takahashi R.
    • Organizer
      The 35^<th> Japanese Congress of Stroke
    • Place of Presentation
      morioka
    • Year and Date
      2010-04-16
    • Related Report
      2010 Final Research Report
  • [Presentation] The effect of telmisartan on chronic cerebral hypoperfusion mouse model.2009

    • Author(s)
      Washida K, Ihara M, Takahashi J, Yamashita J, Ito H, Tomimoto H, Takahashi R.
    • Organizer
      Neuroscience 2009
    • Place of Presentation
      Chicago
    • Year and Date
      2009-10-19
    • Related Report
      2010 Final Research Report
  • [Presentation] The effect of telmisartan on chronic cerebral hypoperfusion mouse model2009

    • Author(s)
      鷲田和夫, 猪原匡史, 高橋淳, 山下潤, 伊東秀文, 冨本秀和, 高橋良輔
    • Organizer
      Neuroscience 2009
    • Place of Presentation
      Chicago
    • Year and Date
      2009-10-19
    • Related Report
      2009 Annual Research Report
  • [Presentation] バイオマトリックスを用いた神経細胞移植2009

    • Author(s)
      吉川達也, 滝和郎, 宮本享, 高橋淳
    • Organizer
      第68回日本脳神経外科学会学術総会
    • Place of Presentation
      東京
    • Year and Date
      2009-10-14
    • Related Report
      2009 Annual Research Report
  • [Presentation] ヒトiPS細胞由来神経幹細胞のマウス脳虚血モデルへの移植2009

    • Author(s)
      五味正憲
    • Organizer
      第10回日本分子脳神経外科学会
    • Place of Presentation
      岡山
    • Year and Date
      2009-09-20
    • Related Report
      2009 Annual Research Report
  • [Presentation] マウス慢性脳低灌流モデルに対する血管前駆細胞移植の効果2009

    • Author(s)
      鷲田和夫, 猪原匡史, 高橋淳, 山下潤, 伊東秀文, 冨本秀和, 高橋良輔
    • Organizer
      日本神経科学大会
    • Place of Presentation
      名古屋
    • Year and Date
      2009-09-16
    • Related Report
      2009 Annual Research Report
  • [Presentation] マウス慢性脳低灌流モデルに対するテルミサルタンの効果2009

    • Author(s)
      鷲田和夫, 猪原匡史, 西尾佳子, 藤田裕之, 高橋淳, 呉暁峰, 木原武士, 伊東秀文, 冨本秀和, 高橋良輔
    • Organizer
      京都脳腎連関分子病態究会
    • Place of Presentation
      京都
    • Year and Date
      2009-09-10
    • Related Report
      2010 Final Research Report
  • [Presentation] 細胞移植による神経再生の将来2009

    • Author(s)
      高橋淳
    • Organizer
      第50回日本神経学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2009-05-21
    • Related Report
      2009 Annual Research Report
  • [Presentation] マウス慢性脳低灌流モデルに対する血管前駆細胞移植の効果2009

    • Author(s)
      鷲田和夫, 猪原匡史, 高橋淳, 山下潤, 伊東秀文, 冨本秀和, 高橋良輔
    • Organizer
      日本神経学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2009-05-20
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] ES細胞研究と臨床への期待2009

    • Author(s)
      高橋淳
    • Organizer
      第29回日本脳神経外科コングレス総会
    • Place of Presentation
      大阪
    • Year and Date
      2009-05-15
    • Related Report
      2009 Annual Research Report
  • [Presentation] Application of ES and iPS cells for the treatment of Parkinson's disease2009

    • Author(s)
      高橋淳
    • Organizer
      The 10^<th> international cell transplant congress
    • Place of Presentation
      Okayama
    • Year and Date
      2009-04-20
    • Related Report
      2009 Annual Research Report
  • [Presentation] 細胞移植による神経再生2009

    • Author(s)
      高橋淳
    • Organizer
      日本医工学治療学会第25回学術大会
    • Place of Presentation
      大阪
    • Year and Date
      2009-04-12
    • Related Report
      2009 Annual Research Report
  • [Presentation] マウス局所脳虚血モデルへのES細胞由来神経幹細胞移植におけるAnti-interleukin-6 receptor antibodyの効果2009

    • Author(s)
      五味正憲, 高橋淳, 丸茂岳, 高木康志
    • Organizer
      第34回日本脳卒中学会
    • Place of Presentation
      松江
    • Year and Date
      2009-03-22
    • Related Report
      2010 Final Research Report
  • [Presentation] 増殖可能なドーパミン神経前駆細胞のヒトES細胞からの誘導2009

    • Author(s)
      森実飛鳥, 高橋淳, Patrik Brundin, Jia-Yi Li
    • Organizer
      第8回日本再生医療学会総会
    • Place of Presentation
      東京
    • Related Report
      2008 Annual Research Report
  • [Presentation] マウス局所脳虚血モデルへのES細胞由来神経幹細胞移植における2009

    • Author(s)
      五味正憲, 高橋淳, 丸茂岳, 高木康志
    • Organizer
      第34回日本脳卒中学会
    • Place of Presentation
      出雲
    • Related Report
      2008 Annual Research Report
  • [Presentation] 髄膜細胞によるES細胞からのドーパミン産生神経誘導2008

    • Author(s)
      高橋淳, 林英樹, 森実飛鳥
    • Organizer
      神経組織の成長・再生・移植研究会第23回学術集会
    • Place of Presentation
      千葉
    • Year and Date
      2008-05-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] 霊長類パーキンソン病モデルに対するヒトES細胞移植2008

    • Author(s)
      土井大輔, 菊地哲広, 斎木英資, 尾上浩隆, 林拓也, 林英樹, 高橋淳
    • Organizer
      神経組織の成長・再生・移植研究会第23回学術集会
    • Place of Presentation
      千葉
    • Year and Date
      2008-05-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] Matrixを用いた細胞移植療法の開発2008

    • Author(s)
      植村真, Mohamed Refaat, 高橋淳
    • Organizer
      神経組織の成長・再生・移植研究会第23回学術集会
    • Place of Presentation
      千葉
    • Year and Date
      2008-05-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] Interleukin-6のES細胞由来神経幹細胞の分化・遊走に対する影響2008

    • Author(s)
      五味正憲、篠山瑞也、高橋淳
    • Organizer
      第9回日本分子脳神経外科学会
    • Place of Presentation
      京都
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] 髄膜細胞によるES細胞からのドーパミン産生神経誘導2008

    • Author(s)
      高橋淳, 林英樹, 森実飛鳥
    • Organizer
      第31回日本神経科学大会
    • Place of Presentation
      東京
    • Related Report
      2008 Annual Research Report
  • [Presentation] ヒト人工多能性幹細胞(iPS細胞)からのドーパミン産生神経誘導2008

    • Author(s)
      高橋淳, 菊地哲広, 土井大輔
    • Organizer
      第67回日本脳神経外科学会
    • Place of Presentation
      盛岡
    • Related Report
      2008 Annual Research Report
  • [Presentation] ヒトES細胞の継代培養数と脳内移植後の生着について2008

    • Author(s)
      森実飛鳥, 高橋淳, Jia-Yi Li, Patrik Brundin
    • Organizer
      第67回日本脳神経外科学会
    • Place of Presentation
      盛岡
    • Related Report
      2008 Annual Research Report
  • [Presentation] Wntシグナルを利用したES細胞からの神経誘導法の開発2008

    • Author(s)
      林英樹, 土井大輔, 高橋淳
    • Organizer
      第67回日本脳神経外科学会
    • Place of Presentation
      盛岡
    • Related Report
      2008 Annual Research Report
  • [Presentation] ES cell transplantation for Parkinson's disease-animal study2008

    • Author(s)
      Jun Takahashi
    • Organizer
      57th Congresso Nazionale Societa Italiana di Neurochirurgia
    • Place of Presentation
      イタリア、ウディネ
    • Related Report
      2008 Annual Research Report
  • [Presentation] Analysis of the human ES cell-derived tumor in the primate model of Parkinson's disease2008

    • Author(s)
      Doi D., KikuchiT., SaikiH., Onoe H., Hayashi T., Hayashi H., Sasai
    • Organizer
      Annual meeting of the Society for Neuroscience 2008
    • Place of Presentation
      米国、ワシントンDC
    • Related Report
      2008 Annual Research Report
  • [Remarks] ホームページ等

    • Related Report
      2010 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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