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Development of pregnancy hypertension model using human placental trophoblast stem cells

Research Project

Project/Area Number 17K19709
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Surgery related to the biological and sensory functions and related fields
Research InstitutionTohoku University

Principal Investigator

Arima Takahiro  東北大学, 医学系研究科, 教授 (80253532)

Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywordsヒト胎盤栄養膜幹細胞 / 妊娠高血圧症候群(HDP) / エピジェネティクス / 妊娠高血圧症
Outline of Final Research Achievements

Recently, social stress and advanced maternal age have increased the frequency of perinatal complications including pregnancy-induced hypertension (PIH) and complete hydatidiform mole (CHM). However, the causes and effective treatments are still unclear. We have succeeded on establishing the human trophoblastic stem cells (TS cells), which show similar cell properties and gene expressions to those of corresponding primary trophoblast cells. In this study, we aim to establish disease TS cells as a PIH and CHM placenta model. We succeeded in establishing in vitro CHM model, which was higher proliferative. Next, we purified the undifferentiated trophoblast cells from the placenta tissues of second and third trimesters of pregnancy. Under the same culture conditions of human TS cells, we made disease TS cells. However, the cell properties and gene expressions were different from those of PIH placenta.

Academic Significance and Societal Importance of the Research Achievements

疾患TS細胞は、in vivoでは不可能であったヒト胎盤形成における分子機構やシグナル伝達機構について詳細に検討することが可能な胎盤細胞ツールとなる。そのため、妊娠高血圧症候群(HDP)などの病態解明などの基礎的研究だけでなく、治療薬剤の開発に応用が期待できる。また、周産期異常となる胎盤異常の治療法の開発に貢献するだけでなく、低出生体重、早産をもたらす他の疾患のモデル細胞作成や病態解明へと道を開くと予想される。これらの成果は、近年増加傾向にある高齢妊娠等を原因とする周産期合併症に対し効果的で、働き盛りの女性の健康増進とQRLの向上に役立つ。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (26 results)

All 2019 2018 2017

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (12 results) (of which Int'l Joint Research: 4 results,  Invited: 10 results) Book (10 results)

  • [Journal Article] Derivation of Human Trophoblast Stem Cells.2018

    • Author(s)
      Okae H, Toh H, Sato T, Hiura H, Takahashi S, Shirane K, Kabayama Y, Suyama M, Sasaki H, Arima T.
    • Journal Title

      Cell Stem Cell.

      Volume: 22 Pages: 50-63

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Derivation of Human Trophoblast Stem Cells2018

    • Author(s)
      Okae Hiroaki、Toh Hidehiro、Sato Tetsuya、Hiura Hitoshi、Takahashi Sota、Shirane Kenjiro、Kabayama Yuka、Suyama Mikita、Sasaki Hiroyuki、Arima Takahiro
    • Journal Title

      Cell Stem Cell

      Volume: 22 Issue: 1 Pages: 50-63.e6

    • DOI

      10.1016/j.stem.2017.11.004

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genome-wide microRNA expression profiling in placentae from frozen-thawed blastocyst transfer2017

    • Author(s)
      Hiura Hitoshi、Hattori Hiromitsu、Kobayashi Norio、Okae Hiroaki、Chiba Hatsune、Miyauchi Naoko、Kitamura Akane、Kikuchi Hiroyuki、Yoshida Hiroaki、Arima Takahiro
    • Journal Title

      Clinical Epigenetics

      Volume: 9 Issue: 1

    • DOI

      10.1186/s13148-017-0379-6

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transcriptomic signature of the follicular somatic compartment surrounding an oocyte with high developmental competence2017

    • Author(s)
      Sugimura Satoshi、Kobayashi Norio、Okae Hiroaki、Yamanouchi Tadayuki、Matsuda Hideo、Kojima Takumi、Yajima Akira、Hashiyada Yutaka、Kaneda Masahiro、Sato Kan、Imai Kei、Tanemura Kentaro、Arima Takahiro、Gilchrist Robert B.
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 6815-6815

    • DOI

      10.1038/s41598-017-07039-5

    • NAID

      120006711707

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] ヒト胎盤幹(TS)細胞の樹立とその細胞特性2019

    • Author(s)
      小林記緒、樋浦仁、岡江寛明、有馬隆博
    • Organizer
      第14回日本生殖発生医学会学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Derivation of Human Trophoblast Stem Cells from Blastocysts and Villous Cytotrophoblast Cells2019

    • Author(s)
      Okae H. ArimaT.
    • Organizer
      International Symposium on Epigenome 2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ヒト胎盤のトロフォブラスト幹細胞の樹立と臨床への応用2018

    • Author(s)
      小林記緒、樋浦仁、岡江寛明、有馬隆博
    • Organizer
      第70回日本産科婦人科学会学術講演会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ARTによるエピジェネティクスの変調2018

    • Author(s)
      小林記緒、樋浦仁、岡江寛明、有馬隆博
    • Organizer
      第63回日本生殖医学会学術講演会・総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Derivation of human trophoblast stem cells.2018

    • Author(s)
      Okae H. ArimaT.
    • Organizer
      Cold Spring Harbor Asia meeting on Stem Cell Crossroads.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Transposable element expression in placental development2018

    • Author(s)
      Nehemiah S. Alvarez, Kesiuke Kozai, Damayanti Chakraborty, Khursheed Iqbal, Kaela M. Varberg, Pavla Brachova, Hiroaki Okae, Takahiro Arima, Gerald G. Schumann, Kathleen H. Burns and Michael J. Soares
    • Organizer
      KEYSTONE SYMPOSIUM 2018
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Derivation of Human Trophoblast Stem Cells from Blastocysts and Villous Cytotrophoblast Cells2017

    • Author(s)
      Arima T, Okae H
    • Organizer
      IHEC Science Days & Annual Meeting 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] ヒト胎盤栄養膜幹細胞の樹立とエピゲノム特性2017

    • Author(s)
      岡江寛明、有馬隆博
    • Organizer
      第25回日本胎盤学会学術集会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 生殖補助医療とヒトインプリンティング疾患2017

    • Author(s)
      有馬隆博、樋浦仁
    • Organizer
      日本人類遺伝学会第62回大会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] ART由来出生児とゲノムインプリンティング2017

    • Author(s)
      有馬隆博
    • Organizer
      第35回日本受精着床学会学術講演会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] ARTとエピジェネティクス2017

    • Author(s)
      有馬隆博
    • Organizer
      第53回日本周産期・新生児医学会学術集会シンポジウム
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] PCBとヒト精子におけるエピジェネティクス2017

    • Author(s)
      有馬隆博
    • Organizer
      第44回日本毒性学会学術年会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Book] ヒト栄養膜幹細胞の樹立.2018

    • Author(s)
      岡江寛明, 有馬隆博.
    • Total Pages
      4
    • Publisher
      羊土社.
    • Related Report
      2018 Annual Research Report
  • [Book] Therapeutic approaches to imprinting diseases.2018

    • Author(s)
      Hattori H, Hiura H, Kobayashi N, Takahashi S, Okae H, Arima T.
    • Total Pages
      6
    • Publisher
      Academic Press.
    • Related Report
      2018 Annual Research Report
  • [Book] 実験医学2018

    • Author(s)
      岡江寛明、有馬隆博
    • Total Pages
      1430
    • Publisher
      羊土社
    • Related Report
      2017 Research-status Report
  • [Book] 新着論文レビュー2018

    • Author(s)
      岡江寛明、有馬隆博
    • Publisher
      ライフサイエンス
    • Related Report
      2017 Research-status Report
  • [Book] 日本周産期・新生児医学会雑誌53巻5号2018

    • Author(s)
      有馬隆博
    • Publisher
      日本周産期・新生児医学会
    • Related Report
      2017 Research-status Report
  • [Book] Epigenetics in Human Disease, Second Edition2018

    • Author(s)
      Hiura H, Hattori H, Kobayashi N, Takahashi S, Okae H, Arima T
    • Publisher
      Elsevier
    • Related Report
      2017 Research-status Report
  • [Book] Handbook of Nutrition, Diet, and Epigenetics2017

    • Author(s)
      Miyauchi N, Kitamura A, Hiura H, Okae H, Kobayashi N, Hattori H, Takahashi S, Arima T
    • Publisher
      Springer International Publishing
    • Related Report
      2017 Research-status Report
  • [Book] 医学のあゆみ ヒトインプリンティング疾患2017

    • Author(s)
      服部裕充、樋浦仁、有馬 隆博
    • Total Pages
      357
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2017 Research-status Report
  • [Book] 先端医療シリーズ48「臨床医のための最新産科婦人科」2017

    • Author(s)
      濱田裕貴、高橋聡太、服部裕充、有馬隆博
    • Total Pages
      529
    • Publisher
      先端医療技術研究所
    • Related Report
      2017 Research-status Report
  • [Book] 産科と婦人科842017

    • Author(s)
      濱田裕貴, 岡江寛明, 有馬隆博
    • Total Pages
      110
    • Publisher
      診断と治療社
    • Related Report
      2017 Research-status Report

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Published: 2017-07-21   Modified: 2020-03-30  

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