Development of an in vitro placentation model to explore the molecular mechanisms of congenital infections

• Project/Area Number: 17K16880
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: National Center for Child Health and Development
• Principal Investigator: Kawasaki Tomoyuki 国立研究開発法人国立成育医療研究センター, 細胞医療研究部, リサーチアソシエイト (90751701)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: iPS細胞 / 胎盤 / 分化誘導 / オルガノイド / 生殖医学 / 幹細胞 / 周産期医学 / 不育症

Outline of Final Research Achievements

We have successfully developed a human placentation model to produce hCG-producing trophoblasts from human induced pluripotent stem (iPS) cells under xeno-free conditions (Lab Invest 2017). It is confirmed that BMP4 is an essential factor for placentation and that the differentiation efficiency varies depending on the concentration and timing of its addition. It succeeded in the differentiation induction of trophoblast syncytiotrophoblast layer (STB) and trophoblast cell layer (CTB). Using this developed human iPS cell trophoblast differentiation induction model, we succeeded in finding two new human placental development biomarkers by comprehensive gene expression analysis (Placenta 2019). It was possible to greatly contribute to the elucidation of the molecular mechanism of the early placental development.

Academic Significance and Societal Importance of the Research Achievements

胎盤の形成過程はブラックボックスに包まれていた。この胎盤の発生を分子レベルで解明するには新たなシステムの構築が必須である。本研究の成果により、異種成分不含で分子解析を恒常的に解析しやすい条件で、ヒト胎盤の初期発生の分子メカニズムを解明する事が可能となるバイオモデルを構築し得た。これを活用し、新たなヒト胎盤のバイオマーカーを見いだすことにも成功し本関連分野の発展に貢献する成果であった。

Research Products

• [Journal Article] Transcriptomic features of trophoblast lineage cells derived from human induced pluripotent stem cells treated with BMP 4 (2020)
  • Author(s): Tsuchida Nanae、Kojima Junya、Fukuda Atsushi、Oda Mayumi、Kawasaki Tomoyuki、Ito Hiroe、Kuji Naoaki、Isaka Keiichi、Nishi Hirotaka、Umezawa Akihiro、Akutsu Hidenori
  • Journal Title: Placenta Volume: 89 Pages: 20-32
  • DOI: 10.1016/j.placenta.2019.10.006
  • Peer Reviewed / Open Access
• [Journal Article] Enhancement of Cellular Adhesion and Proliferation in Human Mesenchymal Stromal Cells by the Direct Addition of Recombinant Collagen I Peptide to the Culture Medium (2019)
  • Author(s): Muraya Koji、Kawasaki Tomoyuki、Yamamoto Takeshi、Akutsu Hidenori
  • Journal Title: BioResearch Open Access Volume: 8 Issue: 1 Pages: 210-218
  • DOI: 10.1089/biores.2019.0012
  • Peer Reviewed / Open Access
• [Journal Article] Efficient production of trophoblast lineage cells from human induced pluripotent stem cells. (2017)
  • Author(s): Kojima J, Fukuda A, Taira H, Kawasaki T, Ito H, Kuji N, Isaka K, Umezawa A, Akutsu H.
  • Journal Title: Lab Invest Volume: 97 Issue: 10 Pages: 1188-1200
  • DOI: 10.1038/labinvest.2016.159
  • Peer Reviewed / Open Access