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Development of a selective culture method for pulmonary epithelial stem cells using high-performance immunotoxin

Research Project

Project/Area Number 18K08151
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53030:Respiratory medicine-related
Research InstitutionSapporo Medical University

Principal Investigator

Yamaguchi Miki  札幌医科大学, 医学部, 助教 (10530454)

Co-Investigator(Kenkyū-buntansha) 佐久間 裕司  札幌医科大学, 医学部, 准教授 (10364514)
内田 宏昭  東京大学, 医科学研究所, 特任准教授 (20401250)
角 俊行  札幌医科大学, 医学部, 研究員 (60772291)
田中 悠祐  札幌医科大学, 医学部, 研究員 (70792125)
多田 周  札幌医科大学, 医学部, 研究員 (00815441)
高橋 素子  札幌医科大学, 医学部, 教授 (00303941)
藤谷 直樹  札幌医科大学, 医学部, 助教 (10374191)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords高性能イミュノトキシン / モノクローナル抗体 / 肺上皮前駆/幹細胞 / 選択な培養 / 慢性閉塞性肺疾患の治療 / 選択的培養 / 肺上皮幹細胞 / イミュノトキシン / 抗体 / 選択的培養法 / 選択的な培養 / 特発性肺線維症の治療
Outline of Final Research Achievements

In the respiratory field, idiopathic pulmonary fibrosis or chronic obstructive pulmonary disease is a chronic progressive disease with a poor prognosis for which no cure has been established. We thought that if the lung epithelial stem cells that make up the lung could be transplanted, it could be a new therapeutic method, and devised a selective culture using immunotoxin. By adding CD90-DT3C (immunotoxin), lung epithelial precursors / stem cells could be selectively cultured. In addition, the culture efficiency was further improved by culturing with the addition of A83-01 and Y27632. From the above, selective culture using immunotoxin was completed. We will proceed with the development of a treatment method for chronic obstructive pulmonary disease using this culture system.

Academic Significance and Societal Importance of the Research Achievements

正常ヒト肺組織由来細胞を用いた肺上皮幹細胞の培養については殆ど報告が無く、イミュノトキシンを利用した細胞の選択については皆無である。イミュノトキシンは内在化能を有する抗体があれば簡単に目的の細胞を排除することができ汎用性がある。この研究が成功することで国内外における培養技術は飛躍的な進化を遂げる可能性がある。
また、高齢者に多発する慢性閉塞性肺疾患の治療に応用可能で治療を受けている国内患者数で約26万人、推定患者数は実に500万人以上である。これらの特発性肺線維症、肺気腫などの慢性閉塞性肺疾患の治療に応用できる可能性が高い。今後は臨床応用に向けた研究を進めたいと考えている。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (2 results)

All 2020 2018

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results)

  • [Journal Article] Pericyte-myofibroblast transition in the human lung2020

    • Author(s)
      Yamaguchi M, Hirai S, Tanaka Y, Sumi T, Tada M, Takahashi H, Watanabe A, Sakuma Y
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 528 Issue: 2 Pages: 269-275

    • DOI

      10.1016/j.bbrc.2020.05.091

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characterization of distal airway stem-like cells expressing N-terminally truncated p63 and thyroid transcription factor-1 in the human lung.2018

    • Author(s)
      Tanaka Y, Yamaguchi M, Hirai S, Sumi T, Tada M, Saito A, Chiba H, Kojima T, Watanabe A, Takahashi H, Sakuma Y.
    • Journal Title

      Exp Cell Res.

      Volume: 372(2) Issue: 2 Pages: 141-149

    • DOI

      10.1016/j.yexcr.2018.09.020

    • Related Report
      2018 Research-status Report
    • Peer Reviewed

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

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