• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2013 Fiscal Year Final Research Report

Reconstitution and functional control of the female reproductive tract through spatiotemporal intervention into the tissue-specific stem cells

Research Project

  • PDF
Project/Area Number 23249076
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKeio University

Principal Investigator

YOSHIMURA Yasunori  慶應義塾大学, 医学部, 教授 (10129736)

Co-Investigator(Kenkyū-buntansha) MARUYAMA Tetsuo  慶應義塾大学, 医学部, 講師 (10209702)
UCHIDA Hiroshi  慶應義塾大学, 医学部, 講師 (90286534)
YAMASAKI Akiko  慶應義塾大学, 医学部, 研究員 (60528777)
MASUDA Hirotaka  慶應義塾大学, 医学部, 助教 (80317198)
Project Period (FY) 2011-04-01 – 2014-03-31
Keywords幹細胞 / 子宮内膜 / 子宮平滑筋 / 子宮内膜症 / 子宮筋腫 / 再生医学 / 脱細胞化
Research Abstract

The aim of this study was to reconstitute normal and abnormal uterus in vivo through spatiotemporal intervention on uterine stem cells. First, we have developed a novel in vivo endometrial stem cell assay using a cell tracking method in combination with an endometrial reconstitution system, which reveals that endometrial side population (ESP) cells are the most likely candidate for endometrial stem cells. The stem cell-like properties of ESP cells suggest their involvement in the pathogenesis of endometriosis. Second, we uncovered a paracrine role of the WNT/beta - Catenin pathway that enables mature myometrial or leiomyoma cells to send mitogenic signals to neighboring tissue stem cells in response to estrogen and progesterone,leading to the growth of uterine leiomyomas. Finally, we have developed decellularization and recellularization techniques for the rat uterus, generating structural and functional uterus in vitro and in vivo.

  • Research Products

    (37 results)

All 2014 2013 2012 2011 2009 Other

All Journal Article (11 results) (of which Peer Reviewed: 11 results) Presentation (21 results) (of which Invited: 11 results) Remarks (2 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 2 results)

  • [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) Pages: 17053-8

    • DOI

      10.1073/pnas.1313650110

    • Peer Reviewed
  • [Journal Article] Possible involvement of nerve growth factor in dysmenorrhea and dyspareunia associated with endometriosis2013

    • 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: 60(10) Pages: 1155-64

    • URL

      https://www.jstage.jst.go.jp/article/endocrj/60/10/60_EJ13-0027/_article

    • Peer Reviewed
  • [Journal Article] The nose knows tubal function?2013

    • Author(s)
      Maruyama T
    • Journal Title

      Fertil Steril

      Volume: 100(2) Pages: 353-354

    • DOI

      10.1016/j.fertnstert.2013.04.026

    • 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: S68-S72

    • DOI

      10.1016/j.placenta.2012.12.010

    • Peer Reviewed
  • [Journal Article] Somatic stem cells in the myometrium and in myomas2013

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

      Semin Reprod Med

      Volume: 31(1) Pages: 77-81

    • DOI

      10.1055/s-0032-1331801

    • 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

      Volume: 18 Pages: 21-25

    • URL

      http://www.seishoku.org/13_18kan/9-frontier1.pdf

    • Peer Reviewed
  • [Journal Article] Stem cell-like differentiation potentials of endometrial side population cells as revealed by a newly developed in vivo endometrial stem cell assay2012

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

      PLoS One

      Volume: 7(12) Pages: e50749

    • DOI

      10.1371/journal.pone.0050749

    • Peer Reviewed
  • [Journal Article] β -Catenin signaling regulates Foxa2 expression during endometrial hyperplasia formation2012

    • Author(s)
      Villacorte M, Suzuki K, Hirasawa A, Ohkawa Y, Suyama M, Maruyama T, Aoki D, Ogino Y, Miyagawa S, Terabayashi T, Tomooka Y, Nakagata N, Yamada G
    • Journal Title

      Oncogene

      Volume: 32 Pages: 3477-3482

    • DOI

      10.1038/onc.2012.376

    • Peer Reviewed
  • [Journal Article] Studies using an in vitro model show evidence of involvement of epithelial-mesenchymal transition of human endometrial epithelial cells in human embryo implantation2012

    • Author(s)
      Uchida H, Maruyama T, Nishikawa-Uchida S, Oda H, Miyazaki K, Yamasaki A, Yoshimura Y
    • Journal Title

      J Biol Chem

      Volume: 287(7) Pages: 4441-4450

    • DOI

      10.1074/jbc.M111.286138

    • Peer Reviewed
  • [Journal Article] Stem cell theory for the pathogenesis of endometriosis2012

    • Author(s)
      Maruyama T, Yoshimura Y
    • Journal Title

      Front Biosci

      Volume: 4 Pages: 2854-2863

    • URL

      http://www.bioscience.org/2012/V4e/af/589/fulltext.htm

    • Peer Reviewed
  • [Journal Article] Establishment of an immortalized human endometrial stromal cell line with functional responses to ovarian stimuli2011

    • Author(s)
      Yuhki M, Kajitani T, Mizuno T, Aoki Y, Maruyama T
    • Journal Title

      Reprod Biol Endocrinol

      Volume: 9 Pages: 104

    • DOI

      10.1186/1477-7827-9-104

    • Peer Reviewed
  • [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
    • Place of Presentation
      鹿児島県鹿児島市・城山観光ホテル
    • Year and Date
      20140125-26
  • [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
    • Place of Presentation
      鹿児島県鹿児島市・城山観光ホテル
    • Year and Date
      20140125-26
  • [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
    • Place of Presentation
      静岡県浜松市・アクトシティ浜松
    • Year and Date
      20131026-27
  • [Presentation] Application of decellularzed rat uterus as a three-dimensional scaffold to in vitro and in vivo uterine tissue engineering2013

    • Author(s)
      Kaoru Miyazaki, Tetsuo Maruyama, Hirotaka Masuda, Naoko Hida, Hiroshi Uchida, Yasunori Yoshimura
    • Organizer
      69th American Society for Reproductive Medicine (ASRM) Annual Meeting
    • Place of Presentation
      Boston, USA
    • Year and Date
      20131012-17
  • [Presentation] Role of stem cells in the pathogenesis of endometriosis : implications for prevention and therapy of endometriosis targeting stem cells2013

    • Author(s)
      Tetsuo Maruyama
    • Organizer
      23th International Conference of Russian Association of Human Reproduction (RAHR)
    • Place of Presentation
      Volgograd, Russia
    • Year and Date
      20130904-07
    • Invited
  • [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
    • Place of Presentation
      宮城県仙台市・仙台国際センター
    • Year and Date
      20130425-27
  • [Presentation] Development of in vivo human endometrial stem cell assay2013

    • Author(s)
      Kaoru Miyazaki, Tetsuo Maruyama, Hirotaka Masuda, Akiko Yamasaki, Sayaka Uchida, Hideyuki Oda, Hiroshi Uchida, and Yasunori Yoshimura
    • Organizer
      60th Annual Meeting of the Society for Gynecologic Investigation(SGI)
    • Place of Presentation
      Orlando, FL, USA
    • Year and Date
      20130320-23
  • [Presentation] Regeneration and reconstruction of the uterus as a future infertility treatment2013

    • Author(s)
      Tetsuo Maruyama
    • Organizer
      International Federation of Fertility Societies (IFFS) Regional Meeting 2014
    • Place of Presentation
      Boston, USA
    • Year and Date
      2013-10-14
    • Invited
  • [Presentation] Differential management of patients with explained and unexplained recurrent pregnancy loss2013

    • Author(s)
      Tetsuo Maruyama
    • Organizer
      The 13th Korea-Japan Joint Conference of Obstetrics and Gynecology
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2013-09-27
    • Invited
  • [Presentation] Human endometrial stem cells; implications for endometrial physiology and pathology2013

    • Author(s)
      Tetsuo Maruyama
    • Organizer
      The 99th Annual Congress of Korean Society of Obstetrics and Gynecology (KSOG)
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2013-09-27
    • Invited
  • [Presentation] Human uterine stem/progenitor cells : implications for uterine physiology and pathology2012

    • Author(s)
      Tetsuo Maruyama
    • Organizer
      18th International Federation of Placenta Association Meeting(IFPA)
    • Place of Presentation
      Hiroshima, Japan
    • Year and Date
      20120918-21
    • Invited
  • [Presentation] ヒト子宮由来幹細胞-何が分かって何ができるか-2012

    • Author(s)
      丸山哲夫
    • Organizer
      第30回日本受精着床学会
    • Place of Presentation
      大阪府大阪市・大阪国際会議場
    • Year and Date
      20120830-31
    • Invited
  • [Presentation] Combined treatment with estrogen and progesterone promotes ectopic survival of intravenously injected human endometrial cells in immunodeficient mice2012

    • Author(s)
      Tetsuo Maruyama, Akiko Yamasaki, Kaoru Miyazaki, Toru Arase, Hiroshi Uchida, Yasunori Yoshimura
    • Organizer
      28th Annual Meeting of European Society of Human Reproduction and Embryology(ESHRE)
    • Place of Presentation
      Istanbul, Turkey
    • Year and Date
      20120701-04
  • [Presentation] Human uterine stem/ progenitor cells2012

    • Author(s)
      Tetsuo Maruyama
    • Organizer
      2nd The State Key Laboratory of Reproductive Biology Symposia in Reproductive Biology(SKLRB)
    • Place of Presentation
      Beijing ,China
    • Year and Date
      20120506-11
    • Invited
  • [Presentation] 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2012

    • 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
    • Organizer
      第17回日本生殖内分泌学会
    • Place of Presentation
      東京都千代田区・サピアタワー
    • Year and Date
      2012-12-08
  • [Presentation] Isolation and characterization of human myometrial stem/progenitor cells : implications for pregnancy-induced myometrial remodeling2012

    • Author(s)
      Tetsuo Maruyama, Masanori Ono, Takashi Kajitani, Hiroshi Uchida, Hideyuki Oda, Sayaka Uchida, Kaoru Miyazaki, Toru Arase, Takashi Nagashima, Hirotaka Masuda, Hideyuki Okano, Yumi Matsuzaki, Yasunori Yoshimura
    • Organizer
      63rd The Korean Society for Reproductive for Reproductive Medicine Meeting(KSRM)
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2012-12-01
    • Invited
  • [Presentation] 成体幹細胞を用いた雌性生殖器官の再生・再建と疾患モデルの構築2012

    • Author(s)
      丸山哲夫
    • Organizer
      第14回神澤医学研究振興財団講演会
    • Place of Presentation
      東京都港区・ホテルオークラ
    • Year and Date
      2012-06-01
    • Invited
  • [Presentation] ヒト子宮幹細胞と臨床医学へのトランスレーション-子宮再生・再建医療への挑戦-2012

    • Author(s)
      丸山哲夫
    • Organizer
      熊本大学授業科目 : 名医に学ぶセミナー
    • Place of Presentation
      熊本県熊本市・熊本大学
    • Year and Date
      2012-02-01
    • Invited
  • [Presentation] Contribution of myometrial stem/progenitor cells to pregnancy-induced uterine remodelling2011

    • Author(s)
      Masanori Ono, Tetsuo Maruyama, Takashi Kajitani, Hiroshi Uchida, Hideyuki Oda, Sayaka Uchida, Toru Arase, Akiko Yamasaki, Takashi Nagashima, Hirotaka Masuda, Yasunori Yoshimura
    • Organizer
      2nd World Congress on Reproductive Biology(WCRB)
    • Place of Presentation
      Cairns, Australia
    • Year and Date
      20111009-12
  • [Presentation] Stem cell theory for the pathogenesis of endometriosis2011

    • Author(s)
      Tetsuo Maruyama
    • Organizer
      22nd Asian and Oceanic Congress of Obstetrics and Gynecology(AOCOG)
    • Place of Presentation
      Taipei, Taiwan
    • Year and Date
      20110923-27
  • [Presentation] Human uterine stem/progenitor cells : implications for uterine physiology and pathology2011

    • Author(s)
      Tetsuo Maruyama
    • Organizer
      Monash Health Translation Precinct (MHTP)
    • Place of Presentation
      Melbourne, Australia
    • Year and Date
      2011-10-06
    • Invited
  • [Remarks] テレビ東京「話題の医学 : ヒト子宮内膜の再生と幹細胞」2012年12月30日午前5~5時15分放映

  • [Remarks] 毎日新聞「部分切除の子宮再生」2014年3月6日

  • [Patent(Industrial Property Rights)] 動物モデルとその作成方法2013

    • Inventor(s)
      丸山哲夫, 升田博隆, 吉村泰典, 岡野栄之, 岡野ジェイムス洋尚, 松崎有美
    • Industrial Property Rights Holder
      学校法人慶應義塾, 公益財団法人実験動物中央研究所
    • Industrial Property Rights Type
      特許権(日本)
    • Industrial Property Number
      特許 5288395号
    • Filing Date
      2013-06-14
  • [Patent(Industrial Property Rights)] 平滑筋幹細胞の単離方法2009

    • Inventor(s)
      丸山哲夫, 小野政徳
    • Industrial Property Rights Holder
      学校法人慶應義塾
    • Industrial Property Rights Type
      特許権(米国)
    • Industrial Property Number
      12/937, 305
    • Filing Date
      2009-04-13
    • Overseas
  • [Patent(Industrial Property Rights)] 平滑筋幹細胞の単離方法2009

    • Inventor(s)
      丸山哲夫, 小野政徳
    • Industrial Property Rights Holder
      学校法人慶應義塾
    • Industrial Property Rights Type
      特許権(中国)
    • Industrial Property Number
      200980121912. 1
    • Filing Date
      2009-04-13
    • Overseas

URL: 

Published: 2015-06-25  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi