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Reconstruction and regeneration of the uterus using decellularization and recellularization techniques

Research Project

Project/Area Number 25670706
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, 講師 (10209702)

Co-Investigator(Kenkyū-buntansha) UCHIDA Hiroshi  慶應義塾大学, 医学部, 講師 (90286534)
MASUDA Hirotaka  慶應義塾大学, 医学部, 助教 (80317198)
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords子宮再生 / 子宮再建 / 組織工学 / 幹細胞 / 脱細胞化 / 再細胞化
Outline of Final Research Achievements

No effective therapies exist for complete loss of uterine structure and/or function. For such patients, genetic motherhood is possible only through gestational surrogacy or uterine transplantation. We here decellularized rat uteri decellularization by aortic perfusion with detergents and produced an underlying extracellular matrix together with an acellular, perfusable vascular architecture. Uterine-like tissues were then regenerated and maintained in vitro for up to 10 d through decellularized uterine matrix (DUM) reseeding with adult and neonatal rat uterine cells and rat mesenchymal stem cells followed by aortic perfusion in a bioreactor. Furthermore, DUM placement onto a partially excised uterus yielded recellularization and regeneration of uterine tissues and achievement of pregnancy nearly comparable to the intact uterus. These results suggest that DUM could be used for uterine regeneration, and provides insights into treatments for uterine factor infertility.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (37 results)

All 2015 2014 2013 Other

All Journal Article (15 results) (of which Peer Reviewed: 14 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (20 results) (of which Invited: 12 results) Book (2 results)

  • [Journal Article] OAT4-mediated transport of olmesartan at basal plasma membrane of human placental barrier.2015

    • Author(s)
      Noguchi S, Nishimura T, Fujibayashi A, Maruyama T, Tomi M, Nakashima E
    • Journal Title

      J Pharm Sci.

      Volume: -

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serum estradiol level during withdrawal bleeding as a predictive factor for intermittent ovarian function in women with primary ovarian insufficiency2015

    • Author(s)
      Miyazaki K, Miki F, Uchida S, Masuda H, Uchida H, Maruyama T
    • Journal Title

      Endocrine Journal

      Volume: 62 Issue: 1 Pages: 93-99

    • DOI

      10.1507/endocrj.EJ14-0189

    • NAID

      130004694069

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Does surgery improve live birth rates in patients with recurrent miscarriage caused by uterine anomalies?2015

    • Author(s)
      Sugiura-Ogasawara M, Lin B-L, Aoki K, Maruyama T, Nakatsuka M, Ozawa N, Sugi T, Takeshita T, Nishida M
    • Journal Title

      J Obstet Gynaecol.

      Volume: 35 Issue: 2 Pages: 155-158

    • DOI

      10.3109/01443615.2014.936839

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tissue-Specific Stem Cells in the Myometrium and Tumor-Initiating Cells in Leiomyoma.2015

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

      Biol Reprod.

      Volume: 91 Issue: 6 Pages: 1-7

    • DOI

      10.1095/biolreprod.114.123794

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genome-wide copy number analysis and systematic mutation screening in 58 patients with hypogonadotropic hypogonadism2014

    • Author(s)
      Izumi Y, Suzuki E, Kanzaki S, Yatsuga S, Kinjo S, Igarashi M, Maruyama T, Sano S, Horikawa R, Sato N, Nakabayashi K, Hata K, Umezawa A, Ogata T, Yoshimura Y, Fukami M
    • Journal Title

      Fertil Steril

      Volume: 102(4) Issue: 4 Pages: 1130-1136

    • DOI

      10.1016/j.fertnstert.2014.06.017

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 【平成26年度日本産科婦人科学会優秀論文賞】 Partial regeneration and reconstruction of the rat uterus through recellularization of a decellularized uterine matrix.2014

    • Author(s)
      Miyazaki K, Maruyama T
    • Journal Title

      Biomaterials.

      Volume: 35 Issue: 31 Pages: 8791-8800

    • DOI

      10.1016/j.biomaterials.2014.06.052

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Endometrial stem / progenitor cells.2014

    • Author(s)
      Maruyama T
    • Journal Title

      J Obstet Gynaecol Res.

      Volume: 40 Issue: 9 Pages: 2015-2022

    • DOI

      10.1111/jog.12501

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] System amino acid transporter SNAT2 shows subtype-specific affinity for betaine and hyperosmotic inducibility in placental trophoblasts.2014

    • Author(s)
      Nishimura T, Yagi R, Usuda M, Oda K, Yamazaki M, Suda S, Takahashi Y, Okazaki F, Sai Y, Higuchi, K, Maruyama T, Tomi M, Nakashima E
    • Journal Title

      Biochim Biophys Acta.

      Volume: VOL. 1838 Issue: 5 Pages: 1306-12

    • DOI

      10.1016/j.bbamem.2014.01.004

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Paracrine activation of WNT/β-catenin pathway in uterine leiomyoma stem cells promotes tumor growth2013

    • Author(s)
      Ono M, Yin P, Navarro A, Moravek MB, Coon JS 5th, Druschitz SA, Serna VA, Qoang W, Brooks DC, Malpani SS, Ma J, Ercan CM, Mittal N, Monsivais D, Dyson MT, Yemelyanov A, Maruyama T, Chkravarti D, Kimm JJ, Kurita T, Gottardi CJ, Bulun SE
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 110(42) Issue: 42 Pages: 17053-8

    • DOI

      10.1073/pnas.1313650110

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Molecular analysis of a mutated FSH receptor detected in a patient with spontaneous ovarian hyperstimulation syndrome.2013

    • Author(s)
      Uchida S, Uchida H, Maruyama T, Kajitani T, Oda H, Miyazaki K, Maki Kagami, Yoshimura Y
    • Journal Title

      PLoS One.

      Volume: VOL. 8 Issue: 9 Pages: e75478-e75478

    • DOI

      10.1371/journal.pone.0075478

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Possible involvement of nerve growth factor in dysmenorrhea and dyspareunia associated with endometriosis.2013

    • Author(s)
      Kajitani T, Maruyama T, Asada H, Uchida H, Oda H, Nishikawa-Uchida S, Miyazaki K, Arase T, Ono M, Yoshimura Y
    • Journal Title

      Endocr J.

      Volume: VOL. 60 Pages: 1155-64

    • NAID

      130004770386

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] The nose knows tubal function?2013

    • Author(s)
      Maruyama T
    • Journal Title

      Fertil Steril

      Volume: 100(2) Issue: 2 Pages: 353-354

    • DOI

      10.1016/j.fertnstert.2013.04.026

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Achievement of pregnancies in women with primary ovarian insufficiency using close monitoring of follicle development: case reports.2013

    • Author(s)
      Maruyama T, Miyazaki K, Uchida H, Uchida S, Masuda H, Yoshimura Y
    • Journal Title

      Endocr J.

      Volume: VOL. 60 Pages: 791-7

    • NAID

      10031184548

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Human uterine stem/ progenitor cells : Implications for uterine physiology and pathology2013

    • Author(s)
      Maruyama T, Miyazaki K, Masuda H, Ono M, Uchida H, Yoshimura Y
    • Journal Title

      Placenta

      Volume: 27 Pages: 77-81

    • DOI

      10.1016/j.placenta.2012.12.010

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] ヒト子宮内膜再構成システムを用いたin vivo幹細胞アッセイの開発と内膜幹細胞の同定.2013

    • Author(s)
      宮崎 薫,丸山哲夫,升田博隆,小田英之,内田明花,内田 浩,吉村泰典
    • Journal Title

      日本生殖内分泌雑誌[平成24年度学術奨励賞受賞]

      Volume: 18巻 Pages: 21-5

    • Related Report
      2013 Research-status Report
  • [Presentation] Decellularization of the rat uterus yielded scaffold capable of tissue regeneration without immune rejection upon allotransplantation.2015

    • Author(s)
      Kaoru Miyazaki, Yuki Ueno, Hirotaka Masuda, Hiroshi Uchida, Tetsuo Maruyama
    • Organizer
      62nd Society for Reproductive Investigation (SRI).
    • Place of Presentation
      San Francisco (USA)
    • Year and Date
      2015-03-25 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] 子宮における幹細胞 ― 雌性生殖器官の再生・再建と疾患メカニズムの解明を目指して ― .2014

    • Author(s)
      丸山哲夫
    • Organizer
      第25回阪大医療組織工学フォーラム
    • Place of Presentation
      大阪大学(大阪府吹田市)
    • Year and Date
      2014-12-05
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Stem/progenitor cells in the human uterus: implications for uterine tumors.2014

    • Author(s)
      Tetsuo Maruyama
    • Organizer
      19th World Congress on Advances in Oncology and 17th International Symposium on Molecular Medicine.
    • Place of Presentation
      Athens (Greece)
    • Year and Date
      2014-10-09
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 【シンポジウム】 幹細胞を用いた子宮内膜の再生・再建.2014

    • Author(s)
      丸山哲夫
    • Organizer
      第87回日本内分泌学会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2014-04-24 – 2014-04-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 幹細胞から見た子宮内膜症の発生・病態メカニズムと治療戦略.2014

    • Author(s)
      丸山哲夫
    • Organizer
      第35回日本エンドメトリオーシス学会[教育講演]
    • Place of Presentation
      城山観光ホテル(鹿児島県鹿児島市)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 希少部位子宮内膜症発生モデルマウスの開発の試み.2014

    • Author(s)
      小田英之,丸山哲夫,山崎彰子,宮崎 薫,荒瀬 透,内田 浩,升田博隆,吉村泰典
    • Organizer
      第35回日本エンドメトリオーシス学会[日本エンドメトリオーシス学会演題発表賞(基礎部門)]
    • Place of Presentation
      城山観光ホテル(鹿児島県鹿児島市)
    • Related Report
      2013 Research-status Report
  • [Presentation] 習慣流産において25(OH)ビタミンDは末梢血NK細胞を抑制する.2013

    • Author(s)
      太田邦明,丸山哲夫,森田峰人,Joanne Kwak-Kim,吉村泰典
    • Organizer
      第28回日本生殖免疫学会[学会賞]
    • Place of Presentation
      平成記念会館(兵庫県西宮市)
    • Related Report
      2013 Research-status Report
  • [Presentation] ベンチサイドから:ヒト子宮幹細胞研究のこれまでと未来予想図.2013

    • Author(s)
      丸山哲夫
    • Organizer
      第126回関東連合産科婦人科学会[ワークショップ]
    • Place of Presentation
      アクトシティ浜松(静岡県浜松市)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Application of decellularzed rat uterus as a three-dimensional scaffold to in vitro and in vivo uterine tissue engineering.2013

    • Author(s)
      Kaoru Miyazaki, Tetsuo Maruyama, Hirotaka Masuda, Naoko Hida, Hiroshi Uchida, Yasunori Yoshimura
    • Organizer
      69th American Society for Reproductive Medicine (ASRM) Annual Meeting.[Society of Reproductive Biologists and Technologists (SRBT) BASIC SCIENCE AWARD]
    • Place of Presentation
      Boston, USA.
    • Related Report
      2013 Research-status Report
  • [Presentation] Role of stem cells in the pathogenesis of endometriosis: implications for prevention and therapy of endometriosis targeting stem cells.2013

    • Author(s)
      Tetsuo Maruyama
    • Organizer
      23th International Conference of Russian Association of Human Reproduction (RAHR)
    • Place of Presentation
      Volgograd, Russia.
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 着床におけるエピジェネティクスと上皮間葉転換(epithelial-to-mesenchymal transition, EMT).2013

    • Author(s)
      丸山哲夫,内田 浩
    • Organizer
      第31回日本受精着床学会[ワークショップ]
    • Place of Presentation
      別府国際コンベンションセンター(大分県別府市)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Novel decellularization and recellularization techniques for reconstruction and regeneration of the uterus in rat.2013

    • Author(s)
      Kaoru Miyazaki, Tetsuo Maruyama, Hirotaka Masuda, Hideyuki Oda, Naoko Hida, Hiroshi Uchida, Yasunori Yoshimura
    • Organizer
      29th Annual Meeting of the European Society of Human Reprodution and Embryology(ESHRE).
    • Place of Presentation
      London, United Kingdom.
    • Related Report
      2013 Research-status Report
  • [Presentation] 脱細胞化マトリックスを用いた子宮の再構築.2013

    • Author(s)
      宮崎 薫,丸山哲夫,升田博隆,内田 浩,吉村泰典
    • Organizer
      第86回日本内分泌学会[若手研究奨励賞(YIA)]
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Related Report
      2013 Research-status Report
  • [Presentation] BMP type II receptor(BMPR2)は着床後の妊娠維持に必須である.

    • Author(s)
      長島 隆,Martin M. Matzuk,丸山哲夫,吉村泰典
    • Organizer
      第18回日本生殖内分泌学会[学術奨励賞]
    • Place of Presentation
      シェーンバッハ・サボー(東京都千代田区)
    • Related Report
      2013 Research-status Report
  • [Presentation] 成人期:早発卵巣不全・早発閉経に関する諸問題.

    • Author(s)
      丸山哲夫
    • Organizer
      第18回日本生殖内分泌学会[シンポジウム]
    • Place of Presentation
      シェーンバッハ・サボー(東京都千代田区)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 自然発症OHSS患者に見いだされた変異FSH受容体の解析.

    • Author(s)
      内田明花,内田 浩,丸山哲夫,梶谷 宇,小田英之,宮崎 薫、各務真紀,吉村泰典
    • Organizer
      第18回日本生殖内分泌学会
    • Place of Presentation
      シェーンバッハ・サボー(東京都千代田区)
    • Related Report
      2013 Research-status Report
  • [Presentation] 子宮・胎盤の炎症とdanger signal.

    • Author(s)
      丸山哲夫
    • Organizer
      第21回日本胎盤学会[ランチョンセミナー]
    • Place of Presentation
      ウィンク愛知(愛知県名古屋市)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Regeneration and reconstruction of the uterus as a future infertility treatment.

    • Author(s)
      Tetsuo Maruyama
    • Organizer
      International Federation of Fertility Societies (IFFS) Regional Meeting 2014.
    • Place of Presentation
      Boston, USA.
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Differential management of patients with explained and unexplained recurrent pregnancy loss.

    • Author(s)
      Tetsuo Maruyama
    • Organizer
      The 13th Korea-Japan Joint Conference of Obstetrics and Gynecology.
    • Place of Presentation
      Seoul, Korea.
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Human endometrial stem cells; implications for endometrial physiology and pathology.

    • Author(s)
      Tetsuo Maruyama
    • Organizer
      The 99th Annual Congress of Korean Society of Obstetrics and Gynecology (KSOG).
    • Place of Presentation
      Seoul, Korea.
    • Related Report
      2013 Research-status Report
    • Invited
  • [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
      2014 Annual Research Report
  • [Book] Endometriosis: Pathogenesis and Treatment2014

    • Author(s)
      Maruyama T
    • Total Pages
      468
    • Publisher
      Springer, Japan.
    • Related Report
      2014 Annual Research Report

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Published: 2014-07-25   Modified: 2019-07-29  

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