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Novel fetal treatment for congenital diaphragmatic hernia using nitrofen induced rat model

Research Project

Project/Area Number 16K20343
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pediatric surgery
Research InstitutionKindai University (2018)
Osaka University (2016-2017)

Principal Investigator

UMEDA Satoshi  近畿大学, 医学部附属病院, 診療講師 (60715176)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords先天性横隔膜ヘルニア / 肺低形成 / 胎児治療 / プロスタサイクリンアゴニスト / 徐放性製剤
Outline of Final Research Achievements

On embryonic day (E) 9.5, nitrofen was given to pregnant Sprague-Dawley rats to establish a CDH-related lung hypoplasia model, whereas normal rats received the vehicle only. The same day, either ONO-1301SR or a placebo was also randomly administered. On E21.5, the fetuses of the normal group and those exhibiting CDH were analyzed. The lung-to-body weight ratio in the CDH+ONO group was greater than that in the CDH group. Histologically, the number of Ttf-1-positive cells and the capillary density were 1.5 times greater in the CDH+ONO group than in the CDH group, and this increase was associated with higher expression of VEGF in the CDH+ONO group, suggesting enhanced development of the alveolar and capillary networks. Thus, prenatal ONO-1301SR was protective against the progression of lung hypoplasia associated with CDH in a nitrofen-induced rat model, indicating the potential of this treatment for pathologies exhibiting lung hypoplasia.

Academic Significance and Societal Importance of the Research Achievements

本研究課題は、先天性横隔膜ヘルニアに伴う肺低形成に対して母体に徐放性製剤を投与することで、児の肺高血圧の治療および低形成肺の成長促進を確認した点に特色がある。これまで、肺低形成の胎児治療としてプロスタサイクリンやその受容体アゴニスト製剤によって胎児治療を試みたという報告はなく、またDDSの投与によって胎児治療を行ったという研究もないため、胎児治療法としても極めて独創的である。本研究成果は、今後先天性横隔膜ヘルニアにおける肺低形成に対する胎児治療の臨床応用に直結できることが期待され、大変意義深いと考えられる。

Report

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

    (2 results)

All 2016

All Presentation (2 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Presentation] Long-term results of tracheoplastyusing collagenous connective tissue membranes (biosheet) in dogs2016

    • Author(s)
      Satoshi Umeda, Yasuhide Nakayama, Yuichi Takama, HiroomiOkuyama
    • Organizer
      5th World Federation of Associations of Pediatric Surgeons
    • Place of Presentation
      Washington DC
    • Year and Date
      2016-10-08
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Prostacyclin agonist 徐放性製剤(ONO-1301SR) を用いた先天性横隔膜ヘルニアにおける新生児・胎児肺低形成に対する新しい胎児治療の開発2016

    • Author(s)
      梅田 聡、宮川 繁、福嶌五月、酒井芳紀、澤 芳樹、奥山宏臣
    • Organizer
      第52回日本周産期・新生児医学会
    • Place of Presentation
      富山
    • Year and Date
      2016-07-16
    • Related Report
      2016 Research-status Report
    • Invited

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Published: 2016-04-21   Modified: 2020-03-30  

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