Development of an artificial womb system to support extremely preterm ovine fetuses

Research Project

Project/Area Number	19K08292
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 52050:Embryonic medicine and pediatrics-related
Research Institution	Tohoku University
Principal Investigator	Watanabe Shimpei 東北大学, 大学病院, 助教 (70509413)
Co-Investigator(Kenkyū-buntansha)	齋藤昌利東北大学, 医学系研究科, 教授 (00451584) 埴田卓志東北大学, 大学病院, 講師 (30400360) 佐藤信一東北大学, 大学病院, 助手 (30770359) 池田秀之東北大学, 大学病院, 助手 (40822888)
Project Period (FY)	2019-04-01 – 2022-03-31
Project Status	Completed (Fiscal Year 2021)
Budget Amount *help	¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000) Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords	人工子宮 / 人工胎盤 / ヒツジ / 子宮内炎症 / 早産児
Outline of Research at the Start	人工子宮システムを用いれば，妊娠90から100日まで (ヒトの妊娠24-27週に相当)，安定した胎児循環のもとで合併症なく，母獣の子宮内で育った胎仔と同等に育てることができることを証明する．また子宮内炎症に曝露された胎仔でも人工子宮システムで安全に成育できることを証明する．
Outline of Final Research Achievements	If an artificial uterine system that can support while maintaining fetal circulation is developed, it may be possible to grow extremely preterm infants without complications and improve the prognosis. The purpose of this study was to clarify its effectiveness. The sheep fetuses were divided into control group (n = 9) that grows in the womb of the native mother and artificial womb group (n = 9) that grows in the artificial womb, and were managed for 120 hours. The survival rate in the artificial uterine system was 87.5%, and there was no significant difference in growth between them. Brain white matter injury was observed in only one fetus who suffered from temporary circulatory insufficiency due to catheter trouble. It was shown that if the device is improved, this system can become a therapeutic device that contributes to the improvement of the prognosis of extremely preterm infants.
Academic Significance and Societal Importance of the Research Achievements	現行の「保育器と呼吸器で育てる新生児集中治療」では，成育限界期に出生する早産児が後遺症なき生存を達成することは難しい．胎児循環から成人循環への転換と未成熟肺での肺呼吸を出生後から強制されるため容易に呼吸循環不全に陥り，脳室内出血，脳白質損傷，壊死性腸炎，慢性肺性心など重篤な合併症を生じるからである．胎児循環を維持しながら成育できる人工子宮システムが開発されれば，超早産児を合併症なく成育でき，予後を改善する可能性がある．本研究により，人工子宮システムが超早産児の予後の改善に寄与する治療デバイスになりうることが示された．