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Use of a human artificial chromosome for delivering trophic factors

Research Project

Project/Area Number 25461315
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionTottori University

Principal Investigator

Watanabe Yasuhiro  鳥取大学, 医学部, 講師 (20335540)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords筋萎縮性側索硬化症 / 人工染色体 / 神経栄養因子 / 細胞移植 / 人口染色体 / 遺伝子治療 / 再生医療 / 細胞治療
Outline of Final Research Achievements

A human artificial chromosome (HAC) can transfer multiple and/or large transgenes along with their regulatory elements thereby resembling native chromosomes. Using this HAC system, we established mesenchymal stem cells (MSCs) that simultaneously expressed hepatocyte growth factor, glial cell line-derived neurotrophic factor and insulin-like growth factor 1, termed HAC-MSCs. We then introduced the cells for the treatment of a neurodegenerative disorder, amyotrophic lateral sclerosis (ALS). The HAC-MSCs were transplanted via the fourth cerebral ventricle (CV) or intravenous (IV) infusion at various ages of recipient mice. We confirmed a statistically significant increase in lifespan via CV transplantation at 100 days compared to the controls. This effect was not seen in mice transplanted with MSCs lacking the HAC. We successfully enhanced the trophic potential of the MSCs using the HAC. This strategy could be a promising direction for the treatment of neurodegenerative disorders.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (9 results)

All 2016 2015 2014 2013

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (5 results) Book (1 results)

  • [Journal Article] Structural basis of Cu, Zn-superoxide dismutase amyloid fibril formation involves interaction of multiple peptide core regions2016

    • Author(s)
      Ida, M. Ando, M. Adachi, M. Tanaka, A. Machida, K. Hongo, K. Mizobata, T. Yamakawa, M. Y. Watanabe, Y. Nakashima, K. Kawata, Y.
    • Journal Title

      Journal of Biochemistry

      Volume: 159 Issue: 2 Pages: 247-260

    • DOI

      10.1093/jb/mvv091

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Use of a Human Artificial Chromosome for Delivering Trophic Factors in a Rodent Model of Amyotrophic Lateral Sclerosis.2015

    • Author(s)
      Watanabe Y, Kazuki Y, Kazuki K, Ebiki M, Nakanishi M, Nakamura K, Yoshida Yamakawa M, Hosokawa H, Ohbayashi T, Oshimura M, Nakashima K.
    • Journal Title

      Mol Ther Nucleic Acids.

      Volume: 4 Pages: e253-e253

    • DOI

      10.1038/mtna.2015.28

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Use of Ramelteon for the Treatment of Secondary REM Sleep Behavior Disorder2013

    • Author(s)
      Nomura T, Kawase S, Watanabe Y, Nakashima K.
    • Journal Title

      Internal Medicine

      Volume: 52 Issue: 18 Pages: 2123-2126

    • DOI

      10.2169/internalmedicine.52.9179

    • NAID

      130003365835

    • ISSN
      0918-2918, 1349-7235
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Optimal conditions for transplantation of mesenchymal stem cells in the ALS model2014

    • Author(s)
      M Ebiki, K Nakamura, Y Watanabe, Y Kazuki, M Yoshida-Yamakawa, H Hosokawa, M Oshimura, K Nakashima
    • Organizer
      25th International Symposium on ALS/MND
    • Place of Presentation
      Brussels, Belgium
    • Year and Date
      2014-12-05 – 2014-12-07
    • Related Report
      2014 Research-status Report
  • [Presentation] 神経栄養因子高発現型間葉系幹細胞のALSモデルマウスへの適正な移植条件の検討2014

    • Author(s)
      恵比木満喬,中村和臣,細川洋行,中西真実,山川三穂,渡辺保裕,中島健二
    • Organizer
      第32回日本神経治療学会総会
    • Place of Presentation
      東京ドームホテル(東京都文京区)
    • Year and Date
      2014-11-20 – 2014-11-22
    • Related Report
      2014 Research-status Report
  • [Presentation] 細胞移植によるALS治療法開発の可能性2014

    • Author(s)
      渡辺保裕
    • Organizer
      筋萎縮側索硬化症(ALS)新規治療法開発をめざした病態解明 平成26年度 ワークショップ
    • Place of Presentation
      都市センターホテル(東京都千代田区)
    • Year and Date
      2014-09-26
    • Related Report
      2014 Research-status Report
  • [Presentation] 人工染色体改変ヒト骨髄間葉系幹細胞を用いたALSモデルマウスに対する細胞移植2013

    • Author(s)
      渡辺保裕,安井建一,中野俊也,中島健二
    • Organizer
      第31回日本神経治療学会総会
    • Place of Presentation
      東京ドームホテル
    • Related Report
      2013 Research-status Report
  • [Presentation] Chromosomally-modified mesenchymal stem cells secreting GDNF, IGF-1, and HGF attenuate disease progression in an ALS animal model2013

    • Author(s)
      Y Watanabe, M Yamakawa, M Ebiki, H Hosokawa, K Yasui, T Nakano, and K Nakashima.
    • Organizer
      24th international symposium on ALS/MND
    • Place of Presentation
      Milan, Italy
    • Related Report
      2013 Research-status Report
  • [Book] 神経症候群(第2版)2014

    • Author(s)
      渡辺保裕,中島健二
    • Total Pages
      5
    • Publisher
      日本臨牀社
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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