Safety assessment of bringing up the sheep fetus with ex vivo uterine environment for a long term

• Project/Area Number: 16K10084
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Tohoku University
• Principal Investigator: WATANABE SHIMPEI 東北大学, 大学病院, 助手 (70509413)
• Co-Investigator(Kenkyū-buntansha): 齋藤 昌利 東北大学, 大学病院, 講師 (00451584) ; 北西 龍太 東北大学, 医学系研究科, 非常勤講師 (20436116) ; 埴田 卓志 東北大学, 大学病院, 助教 (30400360) ; 松田 直 東北大学, 医学系研究科, 非常勤講師 (50361100)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 人工胎盤 / 胎児 / ヒツジ / 早産児

Outline of Final Research Achievements

The study was performed to make clear that whether the fetus treated with ex vivo uterine environment for ten days to expected date of birth could breathe itself. Suffolk ewes with timed were surgically delivered at 136-137 days of gestation (term is 147 days) and their fetuses were adapted to ex vivo uterine environment therapy (treatment group; n=4). During the treatment period, blood lactate levels of all fetuses maintained under 30 mg/dL. After the treatment, the fetuses were delivered from artificial amniotic fluid at 146.0±0.4 days. Control group animals (n=4) were surgically delivered at 145.8±0.3 days.
All fetuses in control group could breathe itself. One of 4 fetuses in the treatment group suffered from severe pneumonia and could not leave the ventilator. The results could suggest that the fetus treated with ex vivo uterine environment for ten days to expected date of birth could breathe itself. However, the management of amniotic fluid pollution remains a challenge.

Academic Significance and Societal Importance of the Research Achievements

超早産児の予後を改善するために人工胎盤システムの開発が進められている．しかし安全性の評価は未だ不十分である．本研究では妊娠満期までの10日間を人工子宮内で成育させたヒツジ胎仔が補助人工換気を要さずに自発呼吸が可能であることが示された．一方で人工羊水の汚染対策，適切な栄養管理に課題が残った．また人工子宮内での胎児発育には適切な人工胎盤血流量の確保が必要であることが示唆された．本研究は人工胎盤システムを超早産児に応用する臨床研究のための橋渡し的研究となった．

Research Products

• [Int'l Joint Research] The University of Western Australia(オーストラリア)
• [Int'l Joint Research] The University of Western Australia(Australia)
• [Journal Article] Successful maintenance of key physiological parameters in preterm lambs treated with ex?vivo uterine environment therapy for a period of 1 week (2017)
  • Author(s): Usuda Haruo、Watanabe Shimpei、Miura Yuichiro、Saito Masatoshi、Musk Gabrielle C.、Rittenschober-B?hm Judith、Ikeda Hideyuki、Sato Shinichi、Hanita Takushi、Matsuda Tadashi、Jobe Alan H.、Newnham John P.、Stock Sarah J.、Kemp Matthew W.
  • Journal Title: Am J Obstet Gynecol. Volume: 217
  • DOI: 10.1016/j.ajog.2017.05.046
  • Peer Reviewed / Int'l Joint Research