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Development of uterine leiomyoma model using CRISPR/CAS9 genome editing system

Research Project

Project/Area Number 15K15610
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Obstetrics and gynecology
Research InstitutionKeio University

Principal Investigator

MARUYAMA Tetsuo  慶應義塾大学, 医学部(信濃町), 准教授 (10209702)

Co-Investigator(Kenkyū-buntansha) 内田 浩  慶應義塾大学, 医学部(信濃町), 講師 (90286534)
升田 博隆  慶應義塾大学, 医学部(信濃町), 講師 (80317198)
小野 政徳  慶應義塾大学, 医学部(信濃町), 共同研究員 (70348712)
荒瀬 透  慶應義塾大学, 医学部(信濃町), 共同研究員 (20348709)
Research Collaborator TAKAO Tomoka  慶應義塾大学, 医学部, 特任助教 (40612429)
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords子宮筋腫 / MED12 / CRISPR/CAS9 / 生殖医学 / 幹細胞医学 / 脱細胞化 / 再細胞化
Outline of Final Research Achievements

Uterine myometrial cells contained a small but significant amount of stem-like cells immediately after isolation from human myometrial tissues. The number of the stem-like cells, however, decreased considerably when they are cultured in vitro. Instead of myometrial stem-like cells, we introduced MED12 mutations, which are observed in approximately 70 % of uterine leiomyomas, into human myometrium cells using CRISPR/CAS9 system, and analyzed hormone-dependent cell proliferation and collagen expression. Preliminary data showed that MED12 mutation did not affect cell growth but tended to induce collagen expression. In vivo leiomyoma model system is under development.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (30 results)

All 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (15 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 12 results,  Acknowledgement Compliant: 3 results,  Open Access: 6 results) Presentation (8 results) (of which Int'l Joint Research: 3 results,  Invited: 5 results) Book (4 results) Remarks (2 results)

  • [Int'l Joint Research] ノースウエスタン大学医学部(米国)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Impact of borderline-subclinical hypothyroidism on subsequent pregnancy outcome in women with unexplained recurrent pregnancy loss.2017

    • Author(s)
      Uchida S, Maruyama T, Kagami M, Miki F, Hihara H, Katakura S, Yoshimasa Y, Masuda H, Uchida H, Tanaka M
    • Journal Title

      J Obstet Gynaecol Res.

      Volume: -

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Contributions of system A subtypes to α-methylaminoisobutyric acid uptake by placental microvillous membranes of human and rat.2017

    • Author(s)
      Takahashi Y, Nishimura T, Maruyama T, Tomi M, Nakashima E
    • Journal Title

      Amino Acids.

      Volume: 49 Issue: 4 Pages: 795-803

    • DOI

      10.1007/s00726-017-2384-7

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Debris makes “MR DC” hustle on endometriosis.2017

    • Author(s)
      Maruyama T
    • Journal Title

      Fertil Steril.

      Volume: 107 Issue: 1 Pages: 68-68

    • DOI

      10.1016/j.fertnstert.2016.10.014

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 産婦人科領域における再生医学・再生医療の現状.2017

    • Author(s)
      丸山哲夫
    • Journal Title

      臨床婦人科産科

      Volume: 71 Pages: 268-272

    • NAID

      40021116711

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Cytogenetic analysis of spontaneously discharged products of conception by array-based comparative genomic hybridization.2016

    • Author(s)
      Ozawa N, Sago H, Matsuoka K, Maruyama T, Migita O, Aizu Y, Inazawa J
    • Journal Title

      SpringerPlus.

      Volume: 5 Issue: 1 Pages: 874-874

    • DOI

      10.1186/s40064-016-2594-6

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bioengineered uterine tissue supports a pregnancy in a rat model.2016

    • Author(s)
      Hellstrom M, Moreno-Moya JM, Bandstein S, Bom E, Akouri RR, Miyazaki K, Maruyama T, Brannstrom M
    • Journal Title

      Fertil Steril.

      Volume: 106 Issue: 2 Pages: 487-496

    • DOI

      10.1016/j.fertnstert.2016.03.048

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] How to create an embryo penetration route.2016

    • Author(s)
      Uchida H, Maruyama T, Masuda H, Uchida S, Miki F, Hihara H, Katakura S, Yoshimasa Y, Tanaka M
    • Journal Title

      Am J Reprod Immunol.

      Volume: 75 Issue: 3 Pages: 326-332

    • DOI

      10.1111/aji.12476

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Endometrial side population cells: potential adult stem/progenitor cells in endometrium.2015

    • Author(s)
      Masuda H, Maruyama T, Gargett C, Miyazaki K, Matsuzaki Y, Okano H, Tanaka M
    • Journal Title

      Biol Reprod

      Volume: 93巻 Issue: 4 Pages: 1-8

    • DOI

      10.1095/biolreprod.115.131490

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Stem cells in the uterus: past, present and future.2015

    • Author(s)
      Maruyama T
    • Journal Title

      Semin Reprod Med

      Volume: 33巻 Issue: 05 Pages: 315-316

    • DOI

      10.1055/s-0035-1563408

    • Related Report
      2015 Research-status Report
  • [Journal Article] Stem cells in endometrial physiology.2015

    • Author(s)
      Gurung S, Deane JA, Masuda H, Maruyama T, Gargett CE
    • Journal Title

      Semin Reprod Med

      Volume: 33巻 Issue: 05 Pages: 326-332

    • DOI

      10.1055/s-0035-1558405

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Uterine leiomyoma stem cells: linking progesterone to growth.2015

    • Author(s)
      Bulun SE, Moravek MB, Yin P, Ono M, Coon V JS, Dyson MT, Antonia N, Marsh EE, Zhao H, Maruyama T, Chakravarti D, Kim JJ, Wei JJ
    • Journal Title

      Semin Reprod Med

      Volume: 33巻 Issue: 05 Pages: 357-365

    • DOI

      10.1055/s-0035-1558451

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cell therapy and tissue engineering from and toward the uterus.2015

    • Author(s)
      Cervello I, Santamaria X, Miyazaki K, Maruyama T, Simon C
    • Journal Title

      Semin Reprod Med

      Volume: 33巻 Issue: 05 Pages: 366-372

    • DOI

      10.1055/s-0035-1559581

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Stem Cells in Myometrial Physiology2015

    • Author(s)
      Ono M, Maruyama T
    • Journal Title

      Semin Reprod Med

      Volume: 33巻 Issue: 05 Pages: 350-356

    • DOI

      10.1055/s-0035-1563602

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] CD34 and CD49f double-positive and lineage marker-negative cells isolated from human myometrium exhibit stem cell-like properties involved in pregnancy-induced uterine remodeling.2015

    • Author(s)
      Ono M, Kajitani T, Uchida H, Arase T, Oda H, Uchida S, Ota K, Nagashima T, Masuda H, Miyazaki K, Asada H, Hida N, Mabuchi Y, Morikawa S, Ito M, Bulun SE, Okano H, Matsuzaki Y, Yoshimura Y, Maruyama T
    • Journal Title

      Biol Reprod

      Volume: 93巻 Issue: 2 Pages: 1-9

    • DOI

      10.1095/biolreprod.114.127126

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ヒト子宮の平滑筋および平滑筋種における幹細胞 ― 妊娠から子宮筋腫まで ―.2015

    • Author(s)
      丸山哲夫,小野政徳
    • Journal Title

      日本生殖内分泌学会雑誌

      Volume: 20巻 Pages: 29-33

    • Related Report
      2015 Research-status Report
  • [Presentation] Role of stem cells in pathophysiology of uterine leiomyoma.2016

    • Author(s)
      Masanori Ono, Tetsuo Maruyama, Mamoru Tanaka, Daisuke Aoki, Serdar E. Bulun
    • Organizer
      5th Asian Conference on Endometriosis (ACE2016)
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Bioengineered uterus and endometrial reconstruction by stem cells.2015

    • Author(s)
      Tetsuo Maruyama
    • Organizer
      21st The International Federation of Gynecology and Obstetrics(FIGO) World Congress of Gynecology and Obstetrics
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2015-10-04
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] [第84回 北里賞受賞講演] 雌性生殖器官の幹細胞システムの解明と再生医学への展開.2015

    • Author(s)
      丸山哲夫
    • Organizer
      第84回北里記念式
    • Place of Presentation
      慶應義塾大学医学部(東京都新宿区)
    • Year and Date
      2015-06-23
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Decellularized uterine matrix can promote uterine regeneration in vivo without immune rejection upon allotransplantation.2015

    • Author(s)
      Kaoru Miyazaki, Yuki Ueno, Hirotaka Masuda, Hiroshi Uchida, Tetsuo Maruyama
    • Organizer
      International Federation of Fertility Societies / Japan Society for Reproductive Medicine (IFFS / JSRM) International Meeting 2015
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2015-04-26
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 脱細胞化と再細胞化による子宮の再構築.2015

    • Author(s)
      宮崎 薫,丸山哲夫
    • Organizer
      第88回日本内分泌学会
    • Place of Presentation
      ホテルニューオータニ(東京都千代田区)
    • Year and Date
      2015-04-23
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 性ステロイドはWNT/β-カテニンシグナルを介して子宮筋腫を発育させる.2015

    • Author(s)
      小野政徳,丸山哲夫,セルダーブルン
    • Organizer
      第88回日本内分泌学会
    • Place of Presentation
      ホテルニューオータニ(東京都千代田区)
    • Year and Date
      2015-04-23
    • Related Report
      2015 Research-status Report
  • [Presentation] 同種異系移植におけるラット子宮脱細胞化マトリックスの免疫原性と再生組織の内分泌学的検討.2015

    • Author(s)
      上野友輝,宮崎 薫,升田博隆,内田 浩,丸山哲夫
    • Organizer
      第88回日本内分泌学会
    • Place of Presentation
      ホテルニューオータニ(東京都千代田区)
    • Year and Date
      2015-04-23
    • Related Report
      2015 Research-status Report
  • [Presentation] ヒト子宮の幹細胞研究の最前線 ~子宮内膜症・子宮筋腫の謎に迫る~ .2015

    • Author(s)
      丸山哲夫
    • Organizer
      北九州産婦人科医会・八幡産婦人科医会学術講演会
    • Place of Presentation
      リーガロイヤルホテル小倉(福岡県北九州市)
    • Year and Date
      2015-04-14
    • Related Report
      2015 Research-status Report
    • Invited
  • [Book] Uterine Fibroids and Adenomyosis2017

    • Author(s)
      Ono M, Maruyama T, Fujiwara H, Bulun SE
    • Publisher
      Springer
    • Related Report
      2016 Annual Research Report
  • [Book] Uterine endometrial Function2016

    • Author(s)
      Maruyama T
    • Total Pages
      155
    • Publisher
      Springer
    • Related Report
      2016 Annual Research Report
  • [Book] Uterine endometrial Function2016

    • Author(s)
      Maruyama T
    • Publisher
      Springer, Japan
    • Related Report
      2015 Research-status Report
  • [Book] 三次元ティッシュエンジニアリング ~ 細胞の培養・操作・組織化から品質管理、脱細胞化まで ~2015

    • Author(s)
      宮崎 薫,丸山哲夫
    • Total Pages
      400
    • Publisher
      エヌ・ティー・エス
    • Related Report
      2015 Research-status Report
  • [Remarks] 慶應義塾大学医学部産婦人科学教室・生殖内分泌研究室

    • URL

      http://www.obgy.med.keio.ac.jp/reearch/03rep-endo.php

    • Related Report
      2016 Annual Research Report
  • [Remarks] 慶應義塾大学医学部 産婦人科学教室ホームページ内 生殖内分泌研究室

    • URL

      http://www.obgy.med.keio.ac.jp/04research/03rep-endo.html

    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2018-03-22  

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