Development of innovative implantation patch for medical treatments of infertility

• Project/Area Number: 25560191
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: The University of Tokyo
• Principal Investigator: Ushida Takashi 東京大学, 工学(系)研究科(研究院), 教授 (50323522)
• Co-Investigator(Kenkyū-buntansha): YOSHINO Osamu 富山大学, 大学院医学薬学研究部(医学), 准教授 (00466757) ; HIROTA Yasushi 東京大学, 医学部付属病院, 講師 (40598653) ; KISHIDA Akio 東京医科歯科大学, 生体材料工学研究所, 教授 (60224929) ; Furukawa Katsuko S 東京大学, 工学(系)研究科(研究院), 准教授 (90343144)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
• Keywords: 子宮再生 / 脱細胞化担体 / 再生医療 / 再生子宮 / 不妊治療 / 超高静水圧

Outline of Final Research Achievements

With the advancement of women in society, women have gradually been wanting to have children at a later age. This dramatic life-style change has resulted in increased infertility, which has become a major problem. In vitro fertilization has made much progress and the success rate has reached the level of natural pregnancies. However, even if a good embryo can be produced, a proper environment for the embryo to attach is essential, and uterine defects are a major cause of failure of in vitro fertilization.
By considering the uterus to be a receptable for the embryo, we adopted a new perspective on uterus regeneration and engineered a novel "uterine embryo implantation patch". Uterine tissues harvested from animals were therefore decellularized, resulting in scaffolds with the same structural and mechanical properties as in vivo tissues. Furthermore, animal experiments showed that, one month after implantation, we had successfully reconstructed uterine tissues with a high pregnancy rate.

Research Products

• [Journal Article] STAT3 accelerates uterine epithelial regeneration in a mouse model of decellularized uterine matrix transplantation. (2016)
  • Author(s): Takehiro Hiraoka,Yasushi Hirota,Tomoko Saito-Fujita,Mitsunori Matsuo,Mahiro Egashira, Leona Matsumoto,Hirofumi Haraguchi, Sudhansu K. Dey,Katsuko S. Furukawa,Tomoyuki Fujii,Yutaka Osuga.
  • Journal Title: Journal of Clinical Investigation Volume: In press
• [Journal Article] Bone regeneration in calvarial defects in a rat model by implantation of human bone marrow-derived mesenchymal stromal cell spheroids (2015)
  • Author(s): Hideyuki Suenaga, Katsuko S. Furukawa, Yukako Suzuki, suyoshi Takato, Takashi Ushida
  • Journal Title: J Mater Sci: Mater Med Volume: 26(11) Issue: 11 Pages: 254-260
  • DOI: 10.1007/s10856-015-5591-3
  • Peer Reviewed
• [Journal Article] Microstereolithography-Based Fabrication of Anatomically Shaped Beta-Tricalcium Phosphate Scaffolds for Bone Tissue Engineering. (2015)
  • Author(s): Dajiang Du, Teruo Asaoka, Makoto Shinohara, Tomonori Kageyama, Takashi Ushida, and Katsuko Sakai Furukawa
  • Journal Title: BioMed Research International Volume: 2015 Pages: 859456-859456
  • DOI: 10.1155/2015/859456
  • Peer Reviewed
• [Journal Article] Modulation of the effect of transforming growth factor-β3 by low-intensity pulsed ultrasound on scaffold-free dedifferentiated articular bovine chondrocyte tissues. (2015)
  • Author(s): Stephanie Yin Wai Ting, Kevin Montagne, Yoshihiro Nishimura, Takashi Ushida1, Katsuko S Furukawa.
  • Journal Title: Tissue Engineering Part C Methods Volume: 21(10) Pages: 1005-1014
  • Peer Reviewed
• [Journal Article] Enhanced chondrogenesis with upregulation of PKR using a novel hydrostatic pressure bioreactor. (2015)
  • Author(s): Jeonghyun Kim, Kevin Montagne, Takashi Ushida, Katsuko Furukawa.
  • Journal Title: Bioscience, Biotechnology, and Biochemistry (BBB) Volume: 79(2) Pages: 239-241
  • Peer Reviewed
• [Journal Article] Decellularization of aorta tissue using sonication treatment as potential scaffold for vascular tissue engineering (2015)
  • Author(s): N Syazwani, A Azhim, Y Morimoto, KS Furukawa, T Ushida
  • Journal Title: Journal of Medical and Biological Engineering Volume: 35 (2) Issue: 2 Pages: 258-269
  • DOI: 10.1007/s40846-015-0028-5
  • Peer Reviewed
• [Journal Article] he use of sonication treatment to decellularize aortic tissues for preparation of bioscaffolds (2014)
  • Author(s): Azhim A, Syazwani N, Morimoto Y, Furukawa K, Ushida T
  • Journal Title: J Biomaterials Volume: 29(1) Pages: 130-141
  • Peer Reviewed
• [Journal Article] Application of detergents or high hydrostatic pressure as decellularization processes in uterine tissues and their subsequent effects on in vivo uterine regeneration in murine models (2014)
  • Author(s): Erna G. Santoso, Keita Yoshida, Yasushi Hirota, Masanori Aizawa, Osamu Yoshino, Akio Kishida, Yutaka Osuga, Shigeru Saito, Takashi Ushida, Katsuko S. Furukawa
  • Journal Title: PLoS ONE Volume: 9(7)
  • Peer Reviewed / Open Access
• [Journal Article] Application of detergents or high hydrostatic pressure as decellularization processes in uterine tissues and their subsequent effects on in vivo uterine regeneration in murine models (2014)
  • Author(s): Erna G. Santoso, Keita Yoshida, Yasushi Hirota, Masanori Aizawa, Osamu Yoshino, Akio Kishida, Yutaka Osuga, Shigeru Saito, Takashi Ushida, Katsuko S. Furukawa
  • Journal Title: PLOS ONE Volume: 印刷中
  • Peer Reviewed
• [Presentation] 脱細胞化担体への間葉系幹細胞播種による子宮組織再生. (2016)
  • Author(s): 関護和,小松寛,吉田圭太,金定賢,廣田泰,吉野修,斎藤滋,岸田晶夫,大須賀穣,牛田多加志,古川克子.
  • Organizer: 第15回日本再生医療学会総会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2016-03-17
• [Presentation] 脱細胞化担体の引張ひずみ印加移植による子宮組織再生 (2016)
  • Author(s): 吉田圭太,関護和,廣田泰,吉野修,齋藤滋,岸田晶夫,大須賀穣,牛田多加志,古川克子.
  • Organizer: 第15回日本再生医療学会総会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2016-03-17
• [Presentation] Promoted differentiation of smooth muscle cells in hMSCs by cyclic stain via the cAMP pathway. (2016)
  • Author(s): Ｊeonghyun Kim,Kevin Montagne,Teemu Mehtonen,Yasushi Hirota,Osamu Yoshino,Shigeru Saito,Yutaka Osuga,Takashi Ushida,Katsuko Furukawa.
  • Organizer: The 15th Congress of Japanese Society for Regenerative Medicine
  • Place of Presentation: International Convention Center（大阪府大阪市）
  • Year and Date: 2016-03-17
• [Presentation] Facilitation of ex vivo synovial joint maturation via dynamic hydrostatic pressure. (2016)
  • Author(s): Andy Tsung Hsun Wu,菊川詢也,Devin Zhang,牛田多加志,古川克子,
  • Organizer: The 15th Congress of Japanese Society for Regenerative Medicine
  • Place of Presentation: International Convention Center（大阪府大阪市）
  • Year and Date: 2016-03-17
• [Presentation] 組織工学技術を用いた子宮パッチの開発. (2016)
  • Author(s): 松永朋浩,古川克子,牛田多加志.
  • Organizer: 日本機械学会関東支部第22期総会・講演会
  • Place of Presentation: 東京工業大学 大岡山キャンパス（東京都目黒区）
  • Year and Date: 2016-03-10
• [Presentation] 血管を保持した脱細胞担体を用いた子宮組織の再生. (2016)
  • Author(s): Mehtonen Teemu,牛田多加志,古川克子.
  • Organizer: 日本機械学会関東支部第22期総会・講演会
  • Place of Presentation: 東京工業大学 大岡山キャンパス（東京都目黒区）
  • Year and Date: 2016-03-10
• [Presentation] 光造形法をにより作製したマイクロパターンによる細胞機能制御. (2016)
  • Author(s): 石橋直也,篠原誠,Montagne Kevin,横田雅代,牛田多加志,古川克子.
  • Organizer: 日本機械学会関東支部第22期総会・講演会
  • Place of Presentation: 東京工業大学 大岡山キャンパス（東京都目黒区）
  • Year and Date: 2016-03-10
• [Presentation] 伸展刺激による細胞接着斑を介した応答のリアルタイムイメージング. (2016)
  • Author(s): 小山暁久,牛田多加志,古川克子.
  • Organizer: 日本機械学会関東支部第22期総会・講演会
  • Place of Presentation: 東京工業大学 大岡山キャンパス（東京都目黒区）
  • Year and Date: 2016-03-10
• [Presentation] ヒト子宮細胞に及ぼすcyclic strainの影響. (2016)
  • Author(s): Kim Jeonghyun,Montagne Kevin,Santoso Erna,Yasushi Hirota,Takehiro Hiraoka,Shigeru Saito,Yutaka Osuga,Takashi Ushida,Katsuko S Furukawa.
  • Organizer: 日本機械学会第28回バイオエンジニアリング講演会
  • Place of Presentation: 東京工業大学 大岡山キャンパス（東京都目黒区）
  • Year and Date: 2016-01-09
• [Presentation] 超高静水圧による脱細胞化担体を用いた子宮組織再生. (2016)
  • Author(s): 関護和,小松寛,吉田圭太,金定賢,廣田泰,吉野修,斉藤滋,岸田晶夫,大須賀穣,牛田多加志,古川克子.
  • Organizer: 日本機械学会第28回バイオエンジニアリング講演会
  • Place of Presentation: 東京工業大学 大岡山キャンパス（東京都目黒区）
  • Year and Date: 2016-01-09
• [Presentation] 繊維状三時限担体を用いた血管組織の生体外構築. (2016)
  • Author(s): 小松寛,小林一穂,渡辺翔太,長南祐美,増本憲泰,戸張悦男,牛田多加志,古川克子.
  • Organizer: 日本機械学会第28回バイオエンジニアリング講演会
  • Place of Presentation: 東京工業大学 大岡山キャンパス（東京都目黒区）
  • Year and Date: 2016-01-09
• [Presentation] 脱細胞化担体による再生子宮の構築. (2015)
  • Author(s): 吉田圭太，古川克子.
  • Organizer: 第53回日本人工臓器学会大会
  • Place of Presentation: 東京ドームホテル（東京都文京区）
  • Year and Date: 2015-11-19
• [Presentation] Uterine tissue engineering by applying cyclic stretching. (2015)
  • Author(s): Jeonghyun Kim, Kevin Montagne,Yasushi Hirota, Takehiro Hiraoka, Osamu Yoshino, Masayo Yokota, Shigeru Saito, Yutaka Osuga, Takashi Ushida, Katsuko S Furukawa.
  • Organizer: 第53回日本人工臓器学会大会
  • Place of Presentation: 東京ドームホテル（東京都文京区）
  • Year and Date: 2015-11-19
• [Presentation] Cyclic Stretching Promoted cAMP Production in Human Endometrial Stromal Cells Leading to Differentiation into Smooth Muscle Cells. (2015)
  • Author(s): Jeonghyun Kim, Kevin Montagne,Yasushi Hirota, Takehiro Hiraoka, Osamu Yoshino, Masayo Yokota, Shigeru Saito, Yutaka Osuga, Takashi Ushida, Katsuko S Furukawa.
  • Organizer: 第42回日本臨床バイオメカニクス学会
  • Place of Presentation: ソラシティカンファレンスセンター（東京都文京区）
  • Year and Date: 2015-11-13
• [Presentation] 材料表面トポロジーによるMSCの骨芽細胞分化コントロール. (2015)
  • Author(s): 古川克子,Seo Chang,Heonuk Jeong,Yue Feng,Kevin Montagne,Yuji Suzuki,牛田多加志.
  • Organizer: 第42回日本臨床バイオメカニクス学会
  • Place of Presentation: ソラシティカンファレンスセンター（東京都文京区）
  • Year and Date: 2015-11-13
• [Presentation] Hydrostatic Pressure Activates Heterotrimeric G Proteins in Chondrocyte Progenitor Cells. (2015)
  • Author(s): Kevin Montagne , Mutsuo Ogasawara , Jeonghyun Kim , Katsuko Furukawa , Takashi Ushida.
  • Organizer: The 8th Asian-Pacific Conference on Biomechanics
  • Place of Presentation: Hokkaido University（北海道札幌市）
  • Year and Date: 2015-09-16
  • Int'l Joint Research
• [Presentation] Cyclic Stretching of Human Endometrial Stromal Cells Promotes Their Differentiation into Smooth Muscle Cells. (2015)
  • Author(s): Jeonghyun Kim, Yasushi Hirota, Takehiro Hiraoka, Osamu Yoshino, Kevin Montagne, Masayo Yokota, Shigeru Saito, Yutaka Osuga, Takashi Ushida, Katsuko S Furukawa.
  • Organizer: The 8th Asian-Pacific Conference on Biomechanics,
  • Place of Presentation: Hokkaido University（北海道札幌市）
  • Year and Date: 2015-09-16
  • Int'l Joint Research
• [Presentation] 間葉系幹細胞への分化誘導を目指した再生子宮の構築 (2015)
  • Author(s): 関護和，渡辺翔太，小松寛，吉田圭太，金定賢，廣田泰，吉野修，斉藤滋，大須賀穣，牛田多加志，古川克子
  • Organizer: 日本機械学会関東支部第２１回総会・講演会
  • Place of Presentation: 横浜国立大学（神奈川県横浜市）
  • Year and Date: 2015-03-20 – 2015-03-21
• [Presentation] 静水圧または薬剤処理による脱細胞化子宮の再生 (2015)
  • Author(s): Furukawa KS, Santoso EG, Yoshida K, Hirota Y, Aizawa M, Yoshino O, Kishida A, Osuga Y, Saito S, Ushida T
  • Organizer: 第１４回日本再生医療学会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2015-03-19 – 2015-03-21
• [Presentation] 脱細胞化担体を用いた子宮組織再生手法の検討 (2015)
  • Author(s): 吉田圭太，中安愛子，関護和，廣田泰，吉野修，岸田晶夫，齋藤滋，大須賀穣，牛田多加志，古川克子
  • Organizer: 日本機械学会第27回バイオエンジニアリング講演会
  • Place of Presentation: 朱鷺メッセ（新潟県）
  • Year and Date: 2015-01-09 – 2015-01-10
• [Presentation] 脱細胞組織担体を用いたラット子宮組織の再生 (2014)
  • Author(s): 吉田圭太，Erna Gondo Santoso，廣田泰，吉野修，根岸淳，岸田晶夫，齋藤滋，大須賀穣，牛田多加志，古川克子
  • Organizer: 日本機械学会第26回バイオエンジニアリング講演会
  • Place of Presentation: 東北大学片平キャンパス（宮城県）
• [Presentation] 動的培養による子宮組織の再構築 (2014)
  • Author(s): 渡辺 翔太, 小林 一穂, Gondo Santoso Erna, 廣田 泰, 吉田 圭太, 吉野 修, 斉藤 滋, 大須賀 穣, 牛田 多加志, 古川 克子
  • Organizer: 日本機械学会関東支部第20期総会・講演会
  • Place of Presentation: 東京農工大学小金井キャンパス（東京都）
• [Presentation] Reconstruction of rat uterine tissue using a decellularized tissue scaffold (2014)
  • Author(s): Erna G. Santoso, Keita Yoshida, Yasushi Hirota, Masanori Aizawa, Osamu Yoshino, Akio Kishida, Yutaka Osuga, Shigeru Saito, Takashi Ushida, Katsuko S. Furukawa
  • Organizer: 第１３回日本再生医療学会総会
  • Place of Presentation: 国立京都国際会館（京都府）
• [Book] HORMONE FRONTIER IN GYNECOLOGY(Vol.23 No.2) (2016)
  • Author(s): 古川克子,廣田泰,吉野修,岸田昌夫,牛田多加志,齋藤滋,大須賀穣.
  • Publisher: メディカルレビュー社
• [Book] メカノバイオロジー－細胞が力を感じ応答する仕組み－第21章 再生医工学におけるメカノバイオロジーＩ (2015)
  • Author(s): 牛田多加志,古川克子他
  • Total Pages: 368
  • Publisher: 化学同人