Transplantation of Multilineage-differentiating stress-enduring cells after spinal cord injury in mice

• Project/Area Number: 17K10917
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Hirosaki University
• Principal Investigator: Kumagai Gentaro 弘前大学, 医学研究科, 講師 (90529679)
• Co-Investigator(Kenkyū-buntansha): 古川 賢一 弘前大学, 医学研究科, 客員研究員 (20165468)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 脊髄損傷 / Muse細胞 / 機能回復 / 細胞移植

Outline of Final Research Achievements

We established the evaluation of anxiety after spinal cord injury (Journal Neurotrauma 2018, 2020 published).
We established mouse adipose tissue-derived Muse cells in vitro. Mouse Muse cells were isolated and characterized for the first time. Muse cells showed greater pluripotency-like characteristics, survival, neurotrophic factor secretion, and neuronal and glialdifferentiation capacities than non-Muse cells, indicating that they may have better neural-regeneration potential (Cell Transplantation 2019 published).

Academic Significance and Societal Importance of the Research Achievements

自家骨髄由来間葉系幹細胞は、札幌医科大学を中心に脊髄損傷に対して、平成25年から平成29年まで医師主導治験が実施され、その有効性が報告されている。一方でヒト骨髄由来Muse細胞も令和1年7月から臨床治験が開始されている。本研究は再生医療研究のプラットフォームであるマウスMuse細胞を確立した。この研究によって詳細なMuse細胞治療効果の検討が可能となる。また、本研究結果から、不安障害は脊髄損傷後の神経障害を悪化させうることが示唆された。この知見は脊髄損傷の実臨床において、非常に役立つ知見と考えられる。

Research Products

• [Journal Article] Neurotrophic Factor Secretion and Neural Differentiation Potential of Multilineage-differentiating Stress-enduring (Muse) Cells Derived from Mouse Adipose Tissue (2019)
  • Author(s): Nitobe Yohshiro、Nagaoki Toshihide、Kumagai Gentaro、Sasaki Ayako、Liu Xizhe、Fujita Taku、Fukutoku Tatsuhiro、Wada Kanichiro、Tanaka Toshihiro、Kudo Hitoshi、Asari Toru、Furukawa Ken-Ichi、Ishibashi Yasuyuki
  • Journal Title: Cell Transplantation Volume: 28 Issue: 9-10 Pages: 1132-1139
  • DOI: 10.1177/0963689719863809
  • Peer Reviewed
• [Journal Article] Poor motor-function recovery after spinal-cord injury in anxiety-model mice with phospholipase related catalytically inactive protein type 1 knockout. (2018)
  • Author(s): Taku Fujita, Gentaro Kumagai
  • Journal Title: Journal of Neurotrauma Volume: 35 Pages: 1379-1386
  • Peer Reviewed / Open Access
• [Journal Article] Poor motor-function recovery after spinal-cord injury in anxiety-model mice with phospholipase related catalytically inactive protein type 1 knockout. (2018)
  • Author(s): Taka Fujita, Gentaro Kumagai, Xizhe Liu, Kanichiro Wada, Toshihiro Tanaka, Hitoshi Kudo, Toru Asari, Tatsuhiro Fukutoku, Ayako Sasaki, Yohshiro Nitobe, Yoshikazu Nikaido, Ken-Ichi Furukawa, Masato Hirata, Takashi Kanematsu, Shinya Ueno, Yasuyuki Ishibash
  • Journal Title: Journal of Neurotrauma Volume: 印刷中 Issue: 12 Pages: 1379-1386
  • DOI: 10.1089/neu.2017.5492
  • Peer Reviewed / Open Access
• [Presentation] Comparison of cell viability and neurotrophic factor between adipose tissue and bone marrow tissue Multilineage-differentiating stress-enduring (Muse) cells (2020)
  • Author(s): Kenya Saruta
  • Organizer: Orthopaedic Research Society
  • Int'l Joint Research
• [Presentation] 脊髄損傷モデルマウスの損傷後の不安障害と運動/感覚機能障害に対する抗不安薬の投与効果 (2019)
  • Author(s): 福徳達宏
  • Organizer: 日本整形外科基礎学会
• [Presentation] The association between anxiety and motor function recovery after spinal cord injury in GABAA receptor-defective mice. (2018)
  • Author(s): Taku Fujita, Gentaro Kumagai et al
  • Organizer: Orthopaedic Research Society Annual Meeting
  • Int'l Joint Research
• [Presentation] A comparison of anxiety behavior after spinal cord injury in female and male mice (2018)
  • Author(s): Tatshuhiro Fukutoku, Gentaro Kumagai et al
  • Organizer: Orthopaedic Research Society Annual Meeting
  • Int'l Joint Research
• [Presentation] マウス脂肪組織由来Multilinage differentiating Stress Enduring (Muse) 細胞と骨髄由来Muse細胞の神経分化能の比較 (2018)
  • Author(s): 長沖隼英、熊谷玄太郎他
  • Organizer: 第33回日本整形外科学会基礎学術集会
• [Presentation] Isolation of Multilineage-differentiating stress enduring cells derived from mouse adipose tissue. (2018)
  • Author(s): Yoshiro Nitobe、Toshihide Nagaoki, Gentaro Kumagai, Ayako Sasaki, Xizhe Liu, Taku Fujita, Kanichiro Wada, Ken-Ichi Furukawa, Yasuyuki Ishibashi
  • Organizer: Orthopeadic Research Society Annual Meeting (国際学会)
  • Int'l Joint Research
• [Presentation] The association between anxiety and motor function recovery after spinal cord injury in GABAA receptor-defective mice. (2018)
  • Author(s): Taku Fujita, Gentaro Kumagai, Xizhe Liu, Kanichiro Wada, Hitoshi Kudo, Asari Toru, Masato Hirata, Takashi Kanematsu, Yoshikazu Nikaido, Shinya Ueno, Yasuyuki Ishibashi
  • Organizer: Orthopaedic Research Society Annual Meeting (国際学会)
• [Presentation] 情動障害マウスにおける脊髄損傷後運動機能回復の検討 (2017)
  • Author(s): 藤田拓、熊谷 玄太郎、劉 希哲、和田 簡一郎、田中 利弘、福徳 達宏、平田 雅人、兼松 隆、二階堂 義和、上野 伸哉、石橋 恭之
  • Organizer: 第32回日本整形外科学会基礎学術集会