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Embryonic implantation organoids using human placental stem cells and challenges to treatment of implantation defects

Research Project

Project/Area Number 21K19546
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 56: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)

Co-Investigator(Kenkyū-buntansha) 小林 記緒  東北大学, 医学系研究科, 助教 (10803885)
小林 枝里  東北大学, 医学系研究科, 助教 (70634971)
Project Period (FY) 2021-07-09 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords生殖補助医療(ART) / 胚着床不全 / 胎盤幹細胞 / オルガノイド
Outline of Research at the Start

晩婚化や初産の高齢化により、生殖補助医療(ART)を選択する患者数は、年々増加傾向にある。しかし、その成功率は改善の余地があり、着床不全の課題がクローズアップされている。我々が独自に樹立に成功したヒト胎盤幹(TS)細胞は、免疫不全マウスに移植すると、着床時にみられる細胞が出現する。そのため、TS細胞は、着床の分子メカニズムの解明だけでなく、着床不全に対する細胞治療として、有用な細胞と期待できる。本研究では、ヒト胚着床オルガノイドモデルを作製し、着床期の分子機構について理解を深めると共に、着床率向上に向けた世界初の細胞療法の有効性について検討する。

Outline of Final Research Achievements

Implantation failure has been identified as a major factor in ART failure rates. Currently, no effective treatment exists. In this study, in order to verify the efficacy of human placental stem (TS) cells against implantation failure in vitro, we have built the embryo-implantation organoid model in which human blastocyst-like structures (blastoids) and endometrial cells coexisted, and based on this model, we clarified that the addition of human TS cells improved the implantation rate (1.8 fold).

Academic Significance and Societal Importance of the Research Achievements

近年、ES細胞に対して自己組織化を促すことで、原腸形成や三胚葉分化などの胚発生過程を模倣するモデルが報告されている。しかしながら、これらのモデルには胎盤系譜の細胞群が欠落しているため、着床後の発生における胎盤発生のモデルにはならない。本研究の最大の特色は、独自に開発したヒトTS細胞の培養技術と遺伝子情報を活用し、世界初の胚着床オルガノイドモデルを作製する点である。またヒトTS細胞は、着床不全に対する革新的な細胞療法として新規性が高く、その期待度も高い。またこのTS療法は、妊娠成功率の飛躍的な向上を図るための先進医療として、少子化対策に貢献するイノベーションになると期待できる。

Report

(3 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (21 results)

All 2023 2022 2021

All Journal Article (8 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 8 results,  Open Access: 8 results) Presentation (6 results) (of which Int'l Joint Research: 6 results,  Invited: 6 results) Book (7 results)

  • [Journal Article] Regulation of human trophoblast gene expression by endogenous retroviruses2023

    • Author(s)
      Frost Jennifer M.、Amante Samuele M.、Okae Hiroaki、Jones Eleri M.、Ashley Brogan、Lewis Rohan M.、Cleal Jane K.、Caley Matthew P.、Arima Takahiro、Maffucci Tania、Branco Miguel R.
    • Journal Title

      Nature Structural & Molecular Biology

      Volume: - Issue: 4 Pages: 527-538

    • DOI

      10.1038/s41594-023-00960-6

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CITED2 is a conserved regulator of the uterine-placental interface.2023

    • Author(s)
      Kuna Marija、Dhakal Pramod、Iqbal Khursheed、Dominguez Esteban M.、Kent Lindsey N.、Muto Masanaga、Moreno-Irusta Ayelen、Kozai Keisuke、Varberg Kaela M.、Okae Hiroaki、Arima Takahiro、Sucov Henry M.、Soares Michael J.
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 120 Issue: 3 Pages: 120-123

    • DOI

      10.1073/pnas.2213622120

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The microRNA cluster C19MC confers differentiation potential into trophoblast lineages upon human pluripotent stem cells2022

    • Author(s)
      Kobayashi Norio、Okae Hiroaki、Hiura Hitoshi、Kubota Naoto、Kobayashi Eri H.、Shibata Shun、Oike Akira、Hori Takeshi、Kikutake Chie、Hamada Hirotaka、Kaji Hirokazu、Suyama Mikita、Bortolin-Cavaill? Marie-Line、Cavaill? J?r?me、Arima Takahiro
    • Journal Title

      Nature Communications

      Volume: 13 Issue: 1 Pages: 3071-3071

    • DOI

      10.1038/s41467-022-30775-w

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Highly rigid H3.1/H3.2-H3K9me3 domains set a barrier for cell fate reprogramming in trophoblast stem cells2022

    • Author(s)
      Hada M, Miura H, Tanigawa A, Matoba S, Inoue K, Ogonuki N, Hirose M, Watanabe N, Nakato R, Fujiki K, Hasegawa A, Sakashita A, Okae H, Miura K, Shikata D, Arima T, Shirahige K, Hiratani I, Ogura A.
    • Journal Title

      Genes Dev

      Volume: 36 Issue: 1-2 Pages: 84-102

    • DOI

      10.1101/gad.348782.121

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The multifaceted role of GCM1 during trophoblast differentiation in the human placenta2022

    • Author(s)
      Jeyarajah Mariyan J.、Jaju Bhattad Gargi、Kelly Rachel D.、Baines Kelly J.、Jaremek Adam、Yang Fei-Hung P.、Okae Hiroaki、Arima Takahiro、Dumeaux Vanessa、Renaud Stephen J.
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 119 Issue: 49

    • DOI

      10.1073/pnas.2203071119

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Intersection of regulatory pathways controlling hemostasis and hemochorial placentation2021

    • Author(s)
      Muto Masanaga、Chakraborty Damayanti、Varberg Kaela M.、Moreno-Irusta Ayelen、Iqbal Khursheed、Scott Regan L.、McNally Ross P.、Choudhury Ruhul H.、Aplin John D.、Okae Hiroaki、Arima Takahiro、Matsumoto Shoma、Ema Masatsugu、Mast Alan E.、Grundberg Elin、Soares Michael J.
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 118 Issue: 50

    • DOI

      10.1073/pnas.2111267118

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ASCL2 reciprocally controls key trophoblast lineage decisions during hemochorial placenta development2021

    • Author(s)
      Varberg Kaela M.、Iqbal Khursheed、Muto Masanaga、Simon Mikaela E.、Scott Regan L.、Kozai Keisuke、Choudhury Ruhul H.、Aplin John D.、Biswell Rebecca、Gibson Margaret、Okae Hiroaki、Arima Takahiro、Vivian Jay L.、Grundberg Elin、Soares Michael J.
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 118 Issue: 10

    • DOI

      10.1073/pnas.2016517118

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Epi-mutations for spermatogenic defects by maternal exposure to di(2-ethylhexyl) phthalate2021

    • Author(s)
      Tando Y, Hiura H, Takehara A, Ito-Matsuoka Y, Arima T, Matsui Y.
    • Journal Title

      Elife .

      Volume: 28

    • DOI

      10.7554/elife.70322

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] ヒト胎盤発生過程におけるエピジェネティクス制御2022

    • Author(s)
      有馬隆博
    • Organizer
      第25回小児分子内分泌研究会
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] マルチオミックス解析による妊娠高血圧症候群の胎盤特性2022

    • Author(s)
      遠藤俊, 柴田峻, 大池輝, 小林枝里, 岡江寛明, 有馬隆博.
    • Organizer
      第30回日本胎盤学会学術集会
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Critical role of genomic imprinting in human placental development2022

    • Author(s)
      Okae H, Arima T
    • Organizer
      The International Symposium "Totipotency and Germ Cell Development"
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Activation of the miRNA cluster C19MC confers differentiation potential into trophoblast lineages upon human pluripotent stem cells2022

    • Author(s)
      Kobayashi N, Okae H, Kaji H, Suyama M, Arima T
    • Organizer
      IHEC2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ヒト胚着床モデル-母胎アセンブロイド-の開発2021

    • Author(s)
      柴田峻、岡江寛明、有馬隆博
    • Organizer
      ART FORUM’21 生殖の分子機構への新たなアプローチ
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 生殖医学研究の最前線 進歩し続ける基礎研究2021

    • Author(s)
      岡江寛明、有馬隆博.
    • Organizer
      66th生殖医学会学術講演会・総会:シンポジウム
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Book] 臨床婦人科産科2022

    • Author(s)
      濱田裕貴, 宮内尚子, 有馬隆博.
    • Total Pages
      6
    • Publisher
      医学書院
    • Related Report
      2022 Annual Research Report
  • [Book] ARTラボ 生殖補助医療の必須知識とラボテクニック2022

    • Author(s)
      服部裕充, 有馬隆博.
    • Total Pages
      5
    • Publisher
      中外医学社
    • Related Report
      2022 Annual Research Report
  • [Book] 生殖補助医療とエピゲノム疾患2021

    • Author(s)
      樋浦仁、服部裕充、有馬隆博
    • Total Pages
      6
    • Publisher
      株式会社メディカルドゥ
    • Related Report
      2021 Research-status Report
  • [Book] ヒト胎盤発生と幹細胞2021

    • Author(s)
      柴田峻、岡江寛明、有馬隆博
    • Total Pages
      5
    • Publisher
      医学書院(金原出版)
    • Related Report
      2021 Research-status Report
  • [Book] ヒト初期発生におけるエピジェネティクス2021

    • Author(s)
      岡江寛明、有馬隆博
    • Total Pages
      6
    • Publisher
      羊土社
    • Related Report
      2021 Research-status Report
  • [Book] トロホブラスト幹細胞と展開2021

    • Author(s)
      小林枝里、岡江寛明、有馬隆博
    • Total Pages
      6
    • Publisher
      メディカルレビュー社
    • Related Report
      2021 Research-status Report
  • [Book] ヒトTS細胞を用いた胎盤疾患モデルの構築2021

    • Author(s)
      大池 輝, 小林 枝里, 小林 記緒, 柴田 峻, 岡江 寛明, 北村 茜, 宮内 尚子, 有馬 隆博
    • Total Pages
      5
    • Publisher
      北隆館/ニューサイエンス社
    • Related Report
      2021 Research-status Report

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Published: 2021-07-13   Modified: 2024-01-30  

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