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トランスクリプトーム解析による移植神経幹細胞のシナプス再生過程の解明

Publicly Offered Research

Project AreaGeneration of synapse-neurocircuit pathology
Project/Area Number 25110725
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKyushu University

Principal Investigator

岡田 誠司  九州大学, 医学(系)研究科(研究院), 准教授 (30448435)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Fiscal Year 2014: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Keywords神経幹細胞 / 脊髄損傷
Outline of Annual Research Achievements

マウス脊髄損傷モデルに対して、移植後に生着した神経幹細胞のみをレーザーマイクロダイセクションを用いて選択的に回収する技術を確立した。これにより、生着した細胞、特に分化ニューロンがどのようなフェノタイプを呈し、どのような機能を持つのかを解析することが可能となった。特に、ホストニューロンをablationした環境に於いては移植の治療効果が消失してしまうこと、さらに生着細胞自身の神経活動マーカやシナプス関連蛋白質の発現が有意に低下することが明らかとなった。すなわち、生着細胞とホストニューロンとのpropriospinal circuitの再構築が移植の治療効果をもたらしている知見が得られた。生着細胞はプレシナプスとポストシナプス蛋白の両者を発現しており、双方向での神経回路を再構築することで、損傷により失われた神経回路修復を試みているものと推測された。シナプス関連分子に関しては興奮性と抑制性のプレシナプス分子を発現していた。また、重度脊髄損傷モデルに於いてはホストニューロンの残存が乏しいため、移植の効果も殆ど認められないことが明らかとなった。この結果は、細胞移植治療を臨床応用する際には重傷度による患者選択が重要であることを示唆している。また、移植細胞同士の神経回路形成が慢性期脊髄損傷や重度脊髄損傷には重要な治療戦略となることが推測されたが、移植細胞同士のシナプス形成は殆ど認められなかった。これは、空間的な近接とシナプス形成に必要なガイダンス分子が重要な役割を果たしていると考えられた。

Research Progress Status

26年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

26年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (20 results)

All 2015 2014 2013

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 2 results,  Acknowledgement Compliant: 3 results) Presentation (10 results) (of which Invited: 4 results)

  • [Journal Article] Spatial re-organization of myogenic regulatory sequences temporally controls gene expression2015

    • Author(s)
      Harada A, Mallappa C, Okada S, Butler JT, Baker SP, Lawrence JB, Ohkawa Y, Imbalzano AN.
    • Journal Title

      Nucleic Acids Research

      Volume: 43 Issue: 4 Pages: 2008-2021

    • DOI

      10.1093/nar/gkv046

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Acute hyperglycemia impairs functional improvement after spinal cord injury in mice and humans2014

    • Author(s)
      Kobayakawa K, Kumamaru H, Saiwai H, Kubota K, Ohkawa Y, Kishimoto J, Yokota K, Ideta R, Shiba K, Tozaki-Saitoh H, Inoue K, Iwamoto Y, Okada S
    • Journal Title

      Science Translational Medicine

      Volume: 6 Issue: 256 Pages: 256-256

    • DOI

      10.1126/scitranslmed.3009430

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Sequential changes of ascending myelopathy after spinal cord injury on MRI.2014

    • Author(s)
      Okada S*, Saito T, Kawano O, Hayashida M, Matsumoto Y, Harimaya K, Iwamoto Y.
    • Journal Title

      Spine Journal.

      Volume: 14 Issue: 12 Pages: e9-e14

    • DOI

      10.1016/j.spinee.2014.08.449

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] A shallow chest correlates with the aortic position in the normal spine:features resembling those observed in structural scoliosis.2014

    • Author(s)
      Doi T, Masumoto Y, Tono O, Tarudado K, Harimaya K, Okada S, Kubota K, Hayashida M, Iwamoto Y.
    • Journal Title

      Scoliosis.

      Volume: 9 Issue: 1 Pages: 14-18

    • DOI

      10.1186/1748-7161-9-14

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Production of a Monoclonal Antibody for C/EBPB : The Subnuclear Localization of C/EBPB in Mouse L929 Cells.2014

    • Author(s)
      Harada A, Okazaki E, Okada S, Tachibana T, Ohkawa Y.
    • Journal Title

      Monoclonal Antibodies Immunodiagnosis and Immunotherapy

      Volume: 33 Issue: 1 Pages: 34-37

    • DOI

      10.1089/mab.2013.0069

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ly6C+ Ly6G- Myeloid-derived suppressor cells play a critical role in the resolution of acute inflammation and the subsequent tissue repair process after spinal cord injury.2013

    • Author(s)
      Saiwai H, Kumamaru H, Ohkawa Y, Kubota K, Kobayakawa K, Yamada H, Yokomizo T, Iwamoto Y, Okada S.
    • Journal Title

      J Neurochem.

      Volume: 125 Issue: 1 Pages: 74-88

    • DOI

      10.1111/jnc.12135

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dedifferentiated chondrosarcoma of the cervical spine: a case report2013

    • Author(s)
      Matsumoto Y, Takahashi Y, Harimaya K, Nakagawa T, Kawaguchi K, Okada S, Hayashida M, Doi T, Sakamoto A, Matsunobu T, Oda Y, Iwamoto Y
    • Journal Title

      World J Surg Oncol

      Volume: 2 Issue: 1 Pages: 32-32

    • DOI

      10.1186/1477-7819-11-32

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Disturbance of ribcage development causes progressive thoracic scoliosis: The creation of a nonsurgical structural scoliosis model in mice.2013

    • Author(s)
      Kubota K, Doi T, Murata M, Kobayakawa K, Matsumoto Y, Harimaya K, Shiba K, Hashizume M, Iwamoto Y, Okada S.
    • Journal Title

      J Bone Joint Surg.

      Volume: 95 Issue: 18 Pages: e130-e130

    • DOI

      10.2106/jbjs.l.01381

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The therapeutic activities of engrafted neural stem/precursor cells are not dormant in the chronically injured spinal cord2013

    • Author(s)
      Kumamaru H, Kobayakawa K, Saiwai H, Kubota K, Yokota K, Ohkawa Y, Shiba K, Iwamoto Y, Okada S
    • Journal Title

      Stem Cells

      Volume: 31(8) Issue: 8 Pages: 1535-47

    • DOI

      10.1002/stem.1404

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical relationship between cervical spinal canal stenosis and traumatic cervical spinal cord injury without major fracture or dislocation.2013

    • Author(s)
      Takao T, Morishita Y, Okada S, Maeda T, Katoh F, Ueta T, Mori E, Yugeu I, Kawano O, Shiba K.
    • Journal Title

      Eur Spine J.

      Volume: 22 Issue: 10 Pages: 2228-2231

    • DOI

      10.1007/s00586-013-2865-7

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] 損傷脊髄環境と移植神経幹細胞の生着率2014

    • Author(s)
      岡田誠司
    • Organizer
      第29回日本整形外科学会基礎学術集会
    • Place of Presentation
      鹿児島
    • Year and Date
      2014-10-09 – 2014-10-10
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 脊髄損傷後の急性期高血糖は運動機能回復を有意に阻害する2014

    • Author(s)
      岡田誠司
    • Organizer
      第49回日本脊髄障害医学会
    • Place of Presentation
      旭川
    • Year and Date
      2014-09-11 – 2014-09-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Limited efficacy of engrafted neural stem and progenitor cells for severe spinal cord injury.2014

    • Author(s)
      Yokota K, Okada S, Kobayakawa K, Saito T, Iwamoto Y.
    • Organizer
      Joint Congress of European Neurology
    • Place of Presentation
      Istanbul, Turkey
    • Year and Date
      2014-05-31 – 2014-06-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] Acute hyperglycemia exacerbates functional outcomes in human and mouse spinal cord injury via NF-kB pathway.2014

    • Author(s)
      Kobayakawa K, Saiwai H, Kumamaru H, Kubota K, Yokota Y, Ohkawa Y, Shiba K, Iwamoto Y, Okada S.
    • Organizer
      Joint Congress of European Neurology
    • Place of Presentation
      Istanbul, Turkey
    • Year and Date
      2014-05-31 – 2014-06-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] 脊髄損傷後の急性期高血糖は運動機能回復を有意に阻害する2014

    • Author(s)
      岡田誠司
    • Organizer
      第87回日本整形外科学術集会
    • Place of Presentation
      神戸
    • Year and Date
      2014-05-23 – 2014-05-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] 脊髄損傷に対する細胞移植治療研究の現状と展望2013

    • Author(s)
      岡田誠司
    • Organizer
      第35回九州理学療法士•作業療法士合同学会(学会基調講演)
    • Place of Presentation
      熊本市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 慢性期脊髄損傷に対する神経幹細胞移植2013

    • Author(s)
      岡田誠司
    • Organizer
      第28回日本整形外科学会基礎学術集会
    • Place of Presentation
      千葉市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 脊髄損傷に対する治験―ステロイド大量療法の歴史から学ぶ2013

    • Author(s)
      岡田誠司
    • Organizer
      第48回日本脊髄障害医学会
    • Place of Presentation
      福岡市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Hyperglycemia-induced microglial overactivation deteriorates the secondary injury via NF-κB pathway after spinal cord injury.2013

    • Author(s)
      Kobayakawa K, Saiwai H, Kumamaru H, Kubota K, Ohkawa Y, Shiba K, Yokota Y, Iwamoto Y, Okada S.
    • Organizer
      The 43th Annual Meeting of Society for Neuroscience
    • Place of Presentation
      San Diego
    • Related Report
      2013 Annual Research Report
  • [Presentation] Structural and functional changes of distal site to the lesion after chronic complete spinal cord injury.2013

    • Author(s)
      Yokota K, Kobayakawa K, Iwamoto Y, Okada S.
    • Organizer
      The 43th Annual Meeting of Society for Neuroscience
    • Place of Presentation
      San Diego
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-15   Modified: 2023-03-16  

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