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Uterine regeneration and development of uterine implantation patch using decellularized matrix and mechanical stimuli

Research Project

Project/Area Number 17J07735
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section国内
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionThe University of Tokyo

Principal Investigator

Kim Jeonghyun  東京大学, 工学系研究科, 特別研究員(PD)

Project Period (FY) 2017-04-26 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥900,000 (Direct Cost: ¥900,000)
Keywordsin vitro model / uterus / implantation / in vitro fertilization / tissue engineering / scaffold-free tissue / Regeneration / Uterus / Embryo / Mechanical stimuli / Scaffold-free tissue / Decellularization
Outline of Annual Research Achievements

本研究では、子宮欠損や不妊の治療に向けて機械的刺激負荷と脱細胞化担体とを複合化することによる子宮組織の再生、および受精卵を着床状態に保持したまま子宮内膜に移植可能な子宮着床パッチを開発することを目的としていた。再細胞化した子宮脱細胞担体を用いるのが望もしいが、Flexcellを用いた周期的伸展刺激を加えるのが困難であった。そこで、組織工学的アプローチによりヒトやラット子宮内膜細胞を用いて3次元構造化形成化(Scaffold-free tissue)に成功した。この新しい3次元モデルを用いラットの子宮に移植実験を行ったところ成功的に子宮再生が行われたことが確認できた。

子宮パッチ開発に必要な足場となるSFTと受精卵を用いたin vitro実験も行った。その結果、SFTにラットの受精卵を共培養させたところ、受精卵の成長率が24時間また48時間で上昇するなどの優位な結果を得た。48時間後には接着した受精卵がSFTに侵入し始める状態も確認でき、受精卵が接着した後のSFTではLIF (Leukemia inhibitor factor)などの遺伝子発現量も優位に上昇した。これらの結果からSFTモデルがin vivoでの受精卵の初期着床と似た現象が観察された。さらに、このSFTを用いFlexcellで周期的伸展刺激を加え実験も進んでいる。HOXA10、HBEGF、ITGB3など胎児が子宮内膜へ着床する時大きく発現する遺伝子が有意に上昇することを明らかにした。機械的刺激が着床へ及ぼすメカニズムを明らかにするデータも得られた。

Research Progress Status

平成30年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

平成30年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (12 results)

All 2018 2017 Other

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

  • [Journal Article] Hypergravity down-regulates c-fos gene expression via ROCK/Rho-GTP and the PI3K signaling pathway in murine ATDC5 chondroprogenitor cells2017

    • Author(s)
      Kim Jeonghyun, Montagne Kevin, Nemoto Hidetoshi, Ushida Takashi and Furukawa Katsuko
    • Journal Title

      PLOS One

      Volume: 12 Issue: 9 Pages: e0185394-e0185394

    • DOI

      10.1371/journal.pone.0185394

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Development of new in vitro model that mimics early implantation of embryo using tissue engineered constructs derived from human endometrial stromal cells2018

    • Author(s)
      Jeonghyun Kim, Takayuki Harada, Yasushi Hirota, Takehiro Hiraoka, Osamu Yoshino, Shigeru Saito, Yutaka Osuga, Takashi Ushida, and Katsuko Furukawa
    • Organizer
      5th TERMIS World Congress - 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Novel application of three-dimensional tissue engineered constructs fabricated by human endometrial stromal cells to facilitate early embryo growth and implantation2018

    • Author(s)
      Jeonghyun Kim, Takayuki Harada, Yasushi Hirota, Takehiro Hiraoka, Osamu Yoshino, Shigeru Saito, Yutaka Osuga, Takashi Ushida, and Katsuko Furukawa
    • Organizer
      8th World Congress of Biomechanics
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] In vitro facilitation of early embryo implantation using three-dimensional tissue-engineered constructs fabricated by human endometrial stromal cells2018

    • Author(s)
      Jeonghyun Kim, Yasushi Hirota, Takehiro Hiraoka, Osamu Yoshino, Shigeru Saito, Yutaka Osuga, Takashi Ushida, and Katsuko Furukawa
    • Organizer
      31th Bioengineering conference of the Japan Society of Mechanical Engineering
    • Related Report
      2018 Annual Research Report
  • [Presentation] Significance of endometrial stromal cells in three-dimensional tissue engineered constructs to facilitate early implantation of embryo2018

    • Author(s)
      Jeonghyun Kim, Takayuki Harada, Matsunaga Tomohiro, Yasushi Hirota, Takehiro Hiraoka, Osamu Yoshino, Shigeru Saito, Yutaka Osuga, Takashi Ushida, and Katsuko Furukawa
    • Organizer
      17th Congress of the Japanese Society for Regenerative Medicine
    • Related Report
      2018 Annual Research Report
  • [Presentation] Reconstruction and in vivo application of scaffold-free tissue using rat endometrial stromal cells2017

    • Author(s)
      Jeonghyun Kim, Takayuki Harada, Tomohiro Matsunaga, Yasushi Hirota, Takehiro Hiraoka, Osamu Yoshino, Shigeru Saito, Yutaka Osuga, Takashi Ushida, Katsuko Furukawa
    • Organizer
      The 26th Congress of the International Society of Biomechanics (ISB 2017)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] In vitro and in vivo application of scaffold-free tissue reconstructed by endometrial stromal cells2017

    • Author(s)
      Jeonghyun Kim, Takayuki Harada, Yasushi Hirota, Takehiro Hiraoka, Osamu Yoshino, Shigeru Saito, Yutaka Osuga, Takashi Ushida, Katsuko Furukawa
    • Organizer
      TERMIS European Chapter Meeting 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Significance of endometrial stromal cells in three-dimensional tissue engineered constructs to facilitate early implantation of embryo2017

    • Author(s)
      Jeonghyun Kim, Takayuki Harada, Matsunaga Tomohiro, Yasushi Hirota, Takehiro Hiraoka, Osamu Yoshino, Shigeru Saito, Yutaka Osuga, Takashi Ushida, Katsuko Furukawa
    • Organizer
      The 17th Congress of the Japanese Society for Regenerative Medicine
    • Related Report
      2017 Annual Research Report
  • [Presentation] Novel approach of scaffold-free tissue using human endometrial stromal cells to facilitate growth of early stage embryo in vitro2017

    • Author(s)
      Jeonghyun Kim, Takayuki Harada, Yasushi Hirota, Takehiro Hiraoka, Osamu Yoshino, Shigeru Saito, Yutaka Osuga, Takashi Ushida, Katsuko Furukawa
    • Organizer
      2017 Annual Meeting of the Japan Society of Mechanical Engineering
    • Related Report
      2017 Annual Research Report
  • [Presentation] Reconstruction of scaffold-free tissue using human endometrial stromal cells2017

    • Author(s)
      Jeonghyun Kim, Matsunaga Tomohiro, Takayuki Harada, Yasushi Hirota, Takehiro Hiraoka, Osamu Yoshino, Shigeru Saito, Yutaka Osuga, Takashi Ushida, Katsuko Furukawa
    • Organizer
      the 16th Congress of the Japanese Society for Regenerative Medicine
    • Related Report
      2017 Annual Research Report
  • [Presentation] Novel method to fabricate scaffold-free tissue using human endometrial stromal cells2017

    • Author(s)
      Jeonghyun Kim, Matsunaga Tomohiro, Yasushi Hirota, Takehiro Hiraoka, Osamu Yoshino, Shigeru Saito, Yutaka Osuga, Takashi Ushida, Katsuko Furukawa
    • Organizer
      The 29th Bioengineering conference of the Japan Society of Mechanical Engineering
    • Related Report
      2017 Annual Research Report
  • [Remarks] 東京大学工学部バイオエンジニアリング専攻牛田・古川研究室

    • URL

      http://www.tissue.t.u-tokyo.ac.jp/index.html

    • Related Report
      2017 Annual Research Report

URL: 

Published: 2017-05-25   Modified: 2024-03-26  

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