Innovative disease modeling of pregnancy complications using human trophoblast stem cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H03072
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Kumamoto University (2022-2023); Tohoku University (2021)
• Principal Investigator: Okae Hiroaki 熊本大学, 発生医学研究所, 教授 (10582695)
• Co-Investigator(Kenkyū-buntansha): 柴田 峻 東北大学, 医学系研究科, 助教 (40885670)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 胎盤 / 妊娠高血圧症候群 / 栄養膜幹細胞（TS細胞）

Outline of Final Research Achievements

This study aims to investigate the pathogenesis of preeclampsia (PE) using human trophoblast stem cells (TSCs). We previously established TSCs from first-trimester human placentas, but it has not been able to apply the same technique to placentas obtained from later developmental stages. In this study, we established a method to establish TSCs from placentas in late gestation by transiently overexpressing SALL4 and a p53 dominant mutant. Next, we established human TSCs from early-onset PE patients and succeeded in recapitulating some key features of PE, such as abnormal secretion of angiogenic factors and abnormal invasion of extravillous cytotrophoblast cells.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

多くの妊娠合併症は妊娠中期以降に発症するが、これまで妊娠中期以降の胎盤細胞を長期培養することはできなかった。本研究で確立したTS細胞の樹立法は、妊娠中期以降の胎盤にも適用することができるため、疾患の発症機構の解析や、医薬品のスクリーニングへの応用が期待される。