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Development of new regenerative technology of spinal cord using autologous cell sheet for severe spinal cord injury.

Research Project

Project/Area Number 15K10417
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Orthopaedic surgery
Research InstitutionNara Medical University

Principal Investigator

Tanaka Yasuhito  奈良県立医科大学, 医学部, 教授 (30316070)

Co-Investigator(Kenkyū-buntansha) 赤羽 学  奈良県立医科大学, 医学部, 准教授 (00418873)
西 真弓  奈良県立医科大学, 医学部, 教授 (40295639)
清水 隆昌  奈良県立医科大学, 医学部, 助教 (70464667)
堀井 謹子  奈良県立医科大学, 医学部, 講師 (80433332)
奥田 哲教  奈良県立医科大学, 医学部, 助教 (80646167)
増田 佳亮  奈良県立医科大学, 医学部附属病院, 研究員 (60790376)
赤羽 学  奈良県立医科大学, 医学部, 准教授 (40326327)
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords脊髄再生 / 再生医療 / 間葉系細胞 / 神経幹細胞 / 細胞シート / 脊髄損傷 / 骨髄間葉系細胞 / 共培養 / 軸索再生 / マクロファージ / グリア瘢痕
Outline of Final Research Achievements

Our study aimed to achieve neural regeneration of completely transected spinal cord injury by using co-culture sheets of bone marrow stromal cells (BMSC) and neural stem cells / progenitor cells (NS / PC). We used rat experimental model. Donor BMSC sheets were obtained from Fisher 344 (F344) rat bone marrow by cell culture in ascorbic acid-added standard medium. NS / PC were obtained from the cortex of fetal brain of E18 pregnant F344 rat. NS / PC was seeded on a BMSC sheet to make a co-culture sheet.
We transected spinal cord of F344 rat at T8 vertebra, and then 2mm defect was made. The co-culture sheet was transplanted to the defect site. Histological evaluation (Tuj1, GFAP, MBP, etc.) and hindlimb motor function evaluation (BBB score) were performed. As a result, it was found that the co-culture sheet promotes neurite outgrowth of neurons and promotes axonal regeneration and remyelination of regenerating axons more than BMSC sheets.

Academic Significance and Societal Importance of the Research Achievements

麻痺を抱えて生活する重症脊髄損傷患者に対して現在治療法がない。本研究で行う新規再生医療技術の開発は麻痺改善や社会復帰を可能とし、中枢神経再生領域の治療法を飛躍的に進歩させる研究である。『他細胞搭載可能な新しいscaffoldとしての細胞シート』の側面もあり、他の再生医療領域への応用も期待され、医学に与えるインパクトは極めて大きいものと確信する。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (21 results)

All 2019 2018 2017 2016 2015

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (19 results) (of which Int'l Joint Research: 4 results)

  • [Journal Article] 骨髄間葉系細胞・神経幹細胞共培養系による細胞シートの開発2017

    • Author(s)
      奥田哲教、堀井謹子、清水隆昌、重松英樹、岩田栄一朗、森本安彦、増田佳亮、赤羽学、西真弓、田中康仁
    • Journal Title

      Journal of Spine Research

      Volume: 8 Pages: 117-122

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Bone marrow stromal cell sheets may promote axonal regeneration and functional recovery with suppression of glial scar formation after spinal cord transection injury in rats.2016

    • Author(s)
      Okuda A*, Horii-Hayashi N, Sasagawa T, Shimizu T, Shigematsu H, Iwata E, Morimoto Y, Masuda K, Koizumi M, Akahane M, Nishi M, Tanaka Y
    • Journal Title

      J Neurosurgery Spine

      Volume: 26 Issue: 3 Pages: 388-395

    • DOI

      10.3171/2016.8.spine16250

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Relationship of Macrophages and Reactive Astrocytes and the Anti-inflammation Effect of Bone Marrow Stromal Cell Sheet at Acute Phase of Transected Spinal Cord Injury in Rats.2019

    • Author(s)
      Keisuke Masuda, Akinori Okuda, Yasuhito Tanaka
    • Organizer
      the annual meeting of Orthopaedic Research Society 2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 骨髄間葉系細胞シートを用いた脊髄損傷治療2018

    • Author(s)
      奥田哲教
    • Organizer
      第33回日本整形外科学会基礎学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 脊髄離断モデルラットへの骨髄間葉系細胞シート移植における軸索再生とグリア瘢痕形成の評価2018

    • Author(s)
      増田佳亮 奥田哲教 田中康仁
    • Organizer
      第33回日本整形外科学会基礎学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 脊髄離断モデルラットへの骨髄間葉系細胞シート移植における軸索再生とグリア瘢痕形成の評価2018

    • Author(s)
      増田佳亮 奥田哲教 田中康仁
    • Organizer
      第91回日本整形外科学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 脊髄離断モデルラットへの骨髄間葉系細胞シート移植における軸索再生とグリア瘢痕形成の評価2018

    • Author(s)
      増田佳亮 奥田哲教 田中康仁
    • Organizer
      第47回日本脊椎脊髄病学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Relationship of Macrophages and Reactive Astrocytes and the Anti-inflammation Effect of Bone Marrow Stromal Cell Sheet at Acute Phase of Transected Spinal Cord Injury in Rats.2018

    • Author(s)
      Keisuke Masuda, Akinori Okuda, Yasuhito Tanaka
    • Organizer
      the annual meeting of Orthopaedic Research Society 2018
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 骨髄間葉系細胞と神経幹・前駆細胞の共培養シート移植による完全離断脊髄損傷ラットの軸索再生と再髄鞘化2017

    • Author(s)
      奥田哲教
    • Organizer
      第90回日本整形外科学会学術集会
    • Place of Presentation
      仙台国際センター
    • Year and Date
      2017-05-18
    • Related Report
      2016 Research-status Report
  • [Presentation] 骨髄間葉系細胞と神経幹・前駆細胞の共培養シート移植による完全離断脊髄損傷ラットの軸索再生と再髄鞘化2017

    • Author(s)
      奥田哲教
    • Organizer
      第46回日本脊椎脊髄病学会
    • Place of Presentation
      ロイトン札幌
    • Year and Date
      2017-04-13
    • Related Report
      2016 Research-status Report
  • [Presentation] Co-culture Cell Sheets of Bone Marrow Stromal Cells and Neural Stem Cells Promote Axonal Regeneration and Remyelination After Completely Transected Spinal Cord Injury In Rats.2017

    • Author(s)
      Akinori Okuda
    • Organizer
      Orthopedic Research Society 2017 annual meeting
    • Place of Presentation
      San Diego Convention Center
    • Year and Date
      2017-03-19
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 骨髄間葉系細胞と神経幹・前駆細胞の共培養シート移植による完全離断脊髄損傷ラットの軸索再生と再髄鞘化2017

    • Author(s)
      奥田哲教 田中康仁
    • Organizer
      第46回日本脊椎脊髄病学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 骨髄間葉系細胞と神経幹・前駆細胞の共培養シート移植による完全離断脊髄損傷ラットの軸索再生と再髄鞘化2017

    • Author(s)
      奥田哲教 田中康仁
    • Organizer
      第90回日本整形外科学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 骨髄間葉系細胞と神経幹・前駆細胞の共培養細胞シート移植による完全離断脊髄損傷ラットの軸索再生と再髄鞘化2017

    • Author(s)
      奥田哲教 田中康仁
    • Organizer
      第32回日本整形外科学会基礎学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 骨髄間葉系細胞と神経幹細胞の共培養細胞シートの開発と脊髄損傷ラットへの移植効果2016

    • Author(s)
      奥田哲教
    • Organizer
      第31回日本整形外科学会基礎学術集会
    • Place of Presentation
      福岡国際会議場
    • Year and Date
      2016-10-13
    • Related Report
      2016 Research-status Report
  • [Presentation] 完全離断脊髄損傷ラットに対する骨髄間葉系細胞シート移植は軸索再生や後肢運動機能改善を起こすが再髄鞘化は起こさない2016

    • Author(s)
      奥田哲教
    • Organizer
      第89回日本整形外科学会学術集会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-05-12
    • Related Report
      2015 Research-status Report
  • [Presentation] 骨髄間葉系細胞と神経幹細胞の共培養細胞シートの開発と脊髄損傷ラットへの移植効果2016

    • Author(s)
      奥田哲教
    • Organizer
      第45回日本脊椎脊髄病学会
    • Place of Presentation
      幕張メッセ
    • Year and Date
      2016-04-14
    • Related Report
      2015 Research-status Report
  • [Presentation] Axonal Regeneration And Hindlimb-functional Recovery By Transplantation Of Bone Marrow Mesenchymal Stromal Cell Sheet After Completely Transected Spinal Cord Injury In Rats.2016

    • Author(s)
      Akinori Okuda
    • Organizer
      Orthopedic Research Society 2016 annual meeting
    • Place of Presentation
      Orland, Florida, USA
    • Year and Date
      2016-03-05
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 骨髄間葉系細胞と神経幹・前駆細胞の共培養シート移植による完全離断脊髄損傷ラットの軸索再生と再髄鞘化2016

    • Author(s)
      奥田哲教
    • Organizer
      第36回整形外科バイオマテリアル研究会
    • Place of Presentation
      大阪大学 銀杏会館
    • Related Report
      2016 Research-status Report
  • [Presentation] 完全離断脊髄損傷ラットに対する骨髄間葉系細胞シート移植は軸索再生や後肢運動機能改善を起こすが再髄鞘化は起こさない2015

    • Author(s)
      奥田哲教
    • Organizer
      第30回日本整形外科学会基礎学術集会
    • Place of Presentation
      富山国際会議場
    • Year and Date
      2015-10-22
    • Related Report
      2015 Research-status Report
  • [Presentation] 脊髄離断モデルラットへの骨髄間葉系細胞シート移植による軸索再生・運動機能改善2015

    • Author(s)
      奥田哲教
    • Organizer
      第44回日本脊椎脊髄病学会
    • Place of Presentation
      福岡国際会議場
    • Year and Date
      2015-04-16
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2020-03-30  

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