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A novel Lentiviral vectors for eliminating tumorigenic cells contaminating in differentiated cells derived from pluripotent stem cells

Research Project

Project/Area Number 18K15853
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53020:Cardiology-related
Research InstitutionKagoshima University

Principal Investigator

Ide Kanako  鹿児島大学, 医歯学総合研究科, 客員研究員 (20725791)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords再生医療 / 腫瘍化阻止 / レンチウイルス / 心筋細胞 / ゲノム編集 / 循環器内科学
Outline of Final Research Achievements

Human pluripotent stem cells (hPSCs) are a promising source of regenerative material for clinical applications. However, hPSC transplant therapies pose the risk of teratoma formation and malignant transformation of undifferentiated remnants. To facilitate safe clinical applications, it is necessary to develop new approaches to directly, completely, and specifically eliminate tumorigenic cells. Here, we developed a novel method for efficiently generating diverse candidates for tumorigenic cell-targeting lentiviral vectors (TC-LVs), enabling systematic identification of the most suitable promoter for this purpose. hPSCs with the suicide gene downstream of the tumor specific promoter, showed undifferentiated cell specific cytotoxic effect and the safety after induction of differentiation into cardiomyocytes. This study demonstrates the utility of this methodology and reveals that the products should pave the way toward safe clinical applications of hPSC-based regenerative medicine.

Academic Significance and Societal Importance of the Research Achievements

本技術は、本邦ならびに世界中で進められている全てのhPSCsでの再生医療研究に応用可能な共通根源の技術であるが、高いオリジナリティーを持ち、ベクター技術は特許取得済みで知財も確保しているため、本邦での再生医療の基礎研究と臨床応用の両面での推進に大きく貢献するものである。本研究により腫瘍化細胞特異的な強力な殺傷効果が得られたことは有意義であり、今後の詳細な解析により期待される成果が得られれば、hPSCsに最も重要な安全性の問題を克服でき、本邦での早期の再生医療の安全かつ着実な実現が可能となるため、先端医療実現による国民福祉の向上と経済発展に繋がる、中長期的には大きな社会貢献の成果が期待できる。

Report

(2 results)
  • 2020 Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (5 results)

All 2019 2018

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] A Novel Construction of Lentiviral Vectors for Eliminating Tumorigenic Cells from Pluripotent Stem Cells.2018

    • Author(s)
      Ide K, Mitsui K, Irie R, Matsushita Y, Ijichi N, Toyodome S, Kosai KI.
    • Journal Title

      Stem Cells

      Volume: 36 Issue: 2 Pages: 230-239

    • DOI

      10.1002/stem.2725

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 多能性幹細胞の腫瘍化完全克服を目指した「ゲノム編集での自殺遺伝子挿入技術」の開発.2019

    • Author(s)
      井手 佳菜子, 豊留 宗一郎, 三井 薫, 松田 恵理子, 小戝 健一郎
    • Organizer
      第18回日本再生医療学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 多能性幹細胞での再生医療に必須となる腫瘍化克服の独自技術の開発2018

    • Author(s)
      井手 佳菜子
    • Organizer
      第3回JSGCT若手研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] A novel construction of lentiviral vectors that identify and eliminate tumorigenic cells from pluripotent stem cells.2018

    • Author(s)
      Kanako Ide, Kaoru Mitsui, Rie Irie, Yohei Matsushita, Nobuhiro Ijichi, Soichiro Toyodome, Eriko Matsuda, Yoshimi Tomiyama and Ken-ichiro Kosai
    • Organizer
      ISSCR2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] ヒト多能性幹細胞の安全領域に長い外来遺伝子を組み込み正常機能させる方法2019

    • Inventor(s)
      小戝健一郎、三井薫、井手佳菜子
    • Industrial Property Rights Holder
      小戝健一郎、三井薫、井手佳菜子
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-030699
    • Filing Date
      2019
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-12-28  

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