The search for the endometrial stem cell marker using the phenome analysis

• Project/Area Number: 24791722
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Keio University
• Principal Investigator: ODA HIDEYUKI 慶應義塾大学, 医学部, 共同研究員 (50445235)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: フェノーム解析 / 子宮内膜幹細胞 / 幹細胞表面抗原マーカー / 遺伝子導入 / 磁力 / 新規子宮内膜移植モデルマウス / 子宮内膜症 / 子宮内膜癌 / モデル動物 / 幹細胞 / 子宮内膜 / フェノーム

Outline of Final Research Achievements

In silico analysis suggested that Fzd5 and LRP6, which are the receptors for Wnt7a, might be one of the candidate markers for the endometrial stem cells.　Both Fzd5- and LRP-positive cells, however, did not reconstruct the endometrium. We then investigated the CD93, which is preferentially expressed in side population cells, but we did not find an association between CD93 and stemness. We next attempted to develop a novel mouse model of endometrial implantation using a lentivirus system to introduce bioluminescent, fluorescent, and cell surface marker genes and to address the in vivo endometrial stem cell activity. Firstly we used human primary endometrial cells, but they showed a very low implantation rate. We, therefore, used a human endometrial cancer cell line and immortalized human endometrial cells and found that they both showed a relatively higher success rate.

Research Products

• [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
  • 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
  • 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
• [Journal Article] ヒト子宮内膜幹細胞の分化能を明らかにするin vivo解析システムの開発． (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: 日本エンドメトリオーシス会誌 Volume: 34巻 Pages: 215-9
• [Journal Article] Stem cell-like differentiation potentials of endometrial side population cells as revealed by a newly developed in vivo endometrial stem cell assay (2012)
  • 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) Issue: 12 Pages: e50749-e50749
  • DOI: 10.1371/journal.pone.0050749
  • Peer Reviewed
• [Journal Article] Involvement of epithelial mesenchymal transition of human endometrial epithelial cells in human embryo implantation : evidence from studies using in vitro model (2012)
  • Author(s): H.Uchida, T.Maruyama, S.Nishikawa-Uchida, H.Oda, K.Miyazaki, A.Yamasaki, Y.Yoshimura
  • Journal Title: Journal of Biological Chemistry Volume: 287 Issue: 7 Pages: 4441-4450
  • DOI: 10.1074/jbc.m111.286138
  • Peer Reviewed
• [Journal Article] Psychological adjustment and psychosocial stress among Japanese couples with a history of recurrent pregnancy loss (2012)
  • Author(s): M.Kagami, T.Maruyama, T.Koizumi, K.Miyazaki, S.Nishikawa-Uchida, H.Oda, H.Uchida, D.Fujisawa, N.Ozawa, L.Schmidt, Y.Yoshimura
  • Journal Title: Human Reproduction Volume: 27 Issue: 3 Pages: 787-794
  • DOI: 10.1093/humrep/der441
  • Peer Reviewed
• [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）
• [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.
• [Presentation] [25 SGI President’s Presenter Awards受賞 ]development of in vivo human endometrial stem vell assay. (2013)
  • Author(s): Kaoru Miyazaki, Tetsuo Maruyama, Hirotaka Masuda, Akiko Yamasaki, Sayaka Uchida, Hideyuki Oda, Hiroshi Uchida, and Yasunori Yoshimura
  • Organizer: 60th Annual Meeting of Society for Gynecologic Investigation(SGI).
  • Place of Presentation: Orlando, FL, USA.
• [Presentation] ヒト子宮内膜幹細胞の分化能を明らかにするin vivo解析システムの開発 (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
  • Organizer: 第34回日本エンドメトリオーシス学会
  • Place of Presentation: 栃木総合文化センター（栃木県）
• [Presentation] [平成24年度学術奨励賞受賞]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: サピアタワー（東京都）
• [Presentation] Isolation and characterization of human myometrial stem/progenitor cells: implications for pregnancy-inuced myometrial remodeling. (2012)
  • Author(s): Tetsuo Maruyama, Masanori Ono, Takashi Kajitani, Hiroshi Uchida, Hideyuki Oda, et al.
  • Organizer: 63rd The Korean Society for Reproductive fo Reproductive Medicine Meeting(KSRM).
  • Place of Presentation: Seoul, Korea.
  • Invited
• [Presentation] ヒト子宮内膜幹細胞の in vivo 解析・同定システムの開発 (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57回日本生殖医学会
  • Place of Presentation: ブリックホール（長崎県）
• [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）