Elucidation of pathological molecular mechanisms involved in pregnancy hypertension using human placental organoid chips

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H03792
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 90110:Biomedical engineering-related
• Research Institution: Tokyo University of Agriculture and Technology
• Principal Investigator: Yoshino Daisuke 東京農工大学, 工学(系)研究科(研究院), 准教授 (80624816)
• Co-Investigator(Kenkyū-buntansha): 郷 勇人 福島県立医科大学, 公私立大学の部局等, 准教授 (30443857) ; 船本 健一 東北大学, 流体科学研究所, 准教授 (70451630)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 胎盤オルガノイド / 高血圧 / 血管障害 / マイクロ流体デバイス / 静水圧

Outline of Final Research Achievements

We designed and fabricated a microfluidic device that mimics human placental structures and constructed placental organoids on a chip using placental choriocarcinoma cell lines and vascular endothelial cells. As a result, cell fusion of placental choriocarcinoma cell lines, formation of complex structures of placental choriocarcinoma cell lines and human umbilical vein endothelial cells, and pregnancy-specific protein expression were achieved. Regarding the mechanism of vascular damage in response to chronic hypertensive stimuli, which was unclear, we were able to identify the expression of blood pressure stimulus-induced apoptosis of vascular endothelial cells and some of the signaling pathways associated with it. On the other hand, due to the difficulty of long-term stable culture of placental organoid chips, we were unable to identify the mechanisms that induce placental and umbilical vascular dysplasia.

Free Research Field

メカノバイオロジー、生体医工学

Academic Significance and Societal Importance of the Research Achievements

本研究では、ヒト胎盤を生体外で再現した機能的な実験モデル“ヒト胎盤オルガノイドチップ”を開発し、持続的な高血圧刺激に対する血管障害のメカニズムについて、血圧刺激誘導性の血管内皮細胞のアポトーシスの発現とそれに関連するシグナル伝達経路の一部を特定することができた。このチップと知見を基盤に、高血圧刺激による血管障害とそれに引き起こされる胎盤・臍帯血管形成不全のメカニズムを明らかにすることで、妊娠高血圧症合併症の治療・予防法開発に繋がる標的分子の特定が可能となる。特定した標的分子を中心に新たな治療法が開発できれば、“安全かつ安心な出産”を実現でき、少子高齢化に悩む我が国に多大な貢献が見込める。