Development of uterus transplantation models in non-human primates

• Project/Area Number: 17H05099
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Obstetrics and gynecology
• Research Institution: Keio University
• Principal Investigator: Kisu Iori 慶應義塾大学, 医学部(信濃町), 特任助教 (30445267)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥24,180,000 (Direct Cost: ¥18,600,000、Indirect Cost: ¥5,580,000); Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2018: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000); Fiscal Year 2017: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
• Keywords: 子宮移植 / 子宮性不妊症 / カニクイザル / 生殖医療 / 移植・再生医療

Outline of Final Research Achievements

Cynomolgus macaques with mismatched and haploidentical MHC and compatible ABO blood type were selected, in which allogenic uterus transplantation were performed. We succeeded in first delivery after recovering from graft rejection and established development of uterus transplantation model in non-human primates.

Academic Significance and Societal Importance of the Research Achievements

霊長類動物での安定した子宮同種移植モデルの作製は前例がなく、その作製の成功により今後の子宮移植の未解決な医学的課題の解明につながる。特にドナーレシピエント間でのHLAマッチングの必要性と免疫応答は臨床応用の最重要課題であり、患者の選択条件などに影響を与えることから、臓器移植領域での学術的意義は大きい。また新たな生殖医療の概念を産婦人科学に生み出すことが期待される。

Research Products

• [Journal Article] Current Progress in Uterus Transplantation Research in Asia. (2019)
  • Author(s): Kisu I, Liu Y, Chen G, Song MJ, Chang CY, Koon TH, Banno K, Aoki D.
  • Journal Title: J Clin Med Volume: 14 Issue: 2 Pages: 245-245
  • DOI: 10.3390/jcm8020245
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Uterus transplantation: advantages and disadvantages of a deceased donor. (2019)
  • Author(s): Kisu I, Banno K, Matoba Y, Aoki D.
  • Journal Title: Arch Gynecol Obstet. Volume: 299 Issue: 5 Pages: 1213-1214
  • DOI: 10.1007/s00404-019-05138-4
  • Peer Reviewed
• [Journal Article] Long-Term Outcome and Rejection After Allogeneic Uterus Transplantation in Cynomolgus Macaques (2019)
  • Author(s): Kisu、Ishigaki、Emoto、Kato、Yamada、Matsubara、Obara、Masugi、Matoba、Adachi、Banno、Saiki、Itagaki、Kawamoto、Iwatani、Nakagawa、Tsuchiya、Sasamura、Urano、Ema、Ogasawara、Aoki、Nakagawa、Shiina
  • Journal Title: Journal of Clinical Medicine Volume: 8 Issue: 10 Pages: 1572-1572
  • DOI: 10.3390/jcm8101572
  • Peer Reviewed / Open Access
• [Journal Article] Re: Rethinking the time interval to embryo transfer after uterus transplantation - DUETS (Dallas UtErus Transplant Study). (2019)
  • Author(s): Kisu I, Banno K, Aoki D.
  • Journal Title: BJOG Volume: 126 Issue: 12 Pages: 1508-1509
  • DOI: 10.1111/1471-0528.15921
  • Peer Reviewed
• [Journal Article] Re: Starting a Uterus transplantation service: Notes from a small island (2018)
  • Author(s): Kisu I, Matoba Y, Banno K, Aoki D
  • Journal Title: BJOG Volume: 125 Issue: 4 Pages: 515-516
  • DOI: 10.1111/1471-0528.15018
  • Peer Reviewed / Open Access
• [Journal Article] Current status of uterus transplantation and approaches for future clinical application in Japan. (2018)
  • Author(s): Kisu I, Banno K, Matoba Y, Adachi M, Aoki D.
  • Journal Title: Transplant Procced Volume: 50 Issue: 9 Pages: 2783-2788
  • DOI: 10.1016/j.transproceed.2018.02.198
  • Peer Reviewed / Open Access
• [Journal Article] Emerging problems in uterus transplantation. (2018)
  • Author(s): Kisu I, Kato Y, Obara H, Matsubara K, Matoba Y, Banno K, Aoki D.
  • Journal Title: BJOG Volume: 125 Issue: 11 Pages: 1352-1356
  • DOI: 10.1111/1471-0528.15230
  • Peer Reviewed / Open Access
• [Journal Article] Basic research on uterus transplantation in non-human primates in Japan. (2018)
  • Author(s): Kisu I, Banno K, Matoba Y, Adachi M, Aoki D.
  • Journal Title: J Obstet Gynaecol Res Volume: 44 Issue: 10 Pages: 1871-1881
  • DOI: 10.1111/jog.13724
  • Peer Reviewed / Open Access
• [Journal Article] 子宮移植の現況と展望 (2018)
  • Author(s): 木須伊織, 的場優介, 阪埜浩司, 青木大輔
  • Journal Title: 日本臨牀 Volume: 76 Pages: 158-164
  • Peer Reviewed
• [Journal Article] 子宮移植 (2018)
  • Author(s): 木須伊織, 的場優介, 阪埜浩司, 青木大輔
  • Journal Title: 産科と婦人科 Volume: 85 Pages: 310-316
  • Peer Reviewed
• [Journal Article] 子宮移植 (2018)
  • Author(s): 木須伊織, 阪埜浩司, 的場優介, 青木大輔
  • Journal Title: 周産期医学 Volume: 48 Pages: 827-832
  • Peer Reviewed
• [Journal Article] 子宮移植：臨床応用に向けて (2018)
  • Author(s): 木須伊織, 阪埜浩司, 青木大輔
  • Journal Title: 日本婦人科腫瘍学会雑誌 Volume: 36 Pages: 243-251
  • Peer Reviewed
• [Journal Article] 子宮移植の現状 (2018)
  • Author(s): 木須伊織
  • Journal Title: 研修ノートNo.100「産婦人科の近未来」日本産婦人科医会 Volume: １ Pages: 23-26
  • Peer Reviewed
• [Journal Article] 子宮移植の現状と展望 (2018)
  • Author(s): 木須 伊織
  • Journal Title: Organ Biology Volume: 25 Pages: 35-40
  • NAID: 130006496761
  • Peer Reviewed
• [Journal Article] 子宮移植 (2017)
  • Author(s): 木須伊織
  • Journal Title: 小児外科 Volume: ４９ Pages: 614-619
  • Peer Reviewed
• [Journal Article] 子宮移植 (2017)
  • Author(s): 木須伊織 , 的場優介、阪埜浩司、青木大輔
  • Journal Title: 産科と婦人科 Volume: 85 Pages: 310-316
  • Peer Reviewed
• [Journal Article] 霊長類動物における子宮移植技術の開発～子宮性不妊症に対する新治療の臨床応用に向けて～ (2017)
  • Author(s): 木須 伊織
  • Journal Title: 日産婦誌 Volume: 69 Pages: 2273-2285
  • Peer Reviewed
• [Journal Article] 子宮移植の世界の現状と課題 (2017)
  • Author(s): 木須伊織, 阪埜浩司, 青木大輔
  • Journal Title: 産婦人科の実際 Volume: 66 Pages: 1833-1838
  • Peer Reviewed
• [Presentation] 生殖医療の最前線：子宮移植の現在と未来 (2019)
  • Author(s): 木須伊織
  • Organizer: 第17回日本生殖看護学会学術集会
  • Invited
• [Presentation] 「移植医療におけるBench to Bedの実際」 (2019)
  • Author(s): 木須伊織, 阪埜浩司, 尾原秀明, 篠田昌宏, 松原健太郎, 山田洋平, 加藤容二郎, 青木大輔
  • Organizer: 第55回日本移植学会総会
• [Presentation] 日本ならびに海外における子宮移植の現状 (2019)
  • Author(s): 木須伊織
  • Organizer: 第8回日本子宮移植研究会学術講演会・市民公開講座
  • Invited
• [Presentation] Current status of uterus transplantation research in Japan: towards clinical application (2018)
  • Author(s): Kisu I, Banno K, Matoba Y, Adachi M, Aoki D
  • Organizer: 第70回日本産科婦人科学会学術講演会
  • Invited
• [Presentation] 非ヒト霊長類動物を用いた子宮同種移植における血管吻合の検討－脳死ドナー想定実験モデルの作製 (2018)
  • Author(s): 木須伊織, 阪埜浩司, 的場優介, 安達将隆, 梅根紀代子, 野上侑哉, 中村加奈子, 小林佑介, 冨永英一郎, 田中守, 青木大輔
  • Organizer: 第70回日本産科婦人科学会学術講演会
• [Presentation] 子宮移植 (2018)
  • Author(s): 木須伊織
  • Organizer: ARTナース医学セミナー2018
  • Invited
• [Presentation] 子宮移植：新たな生殖・移植医療技術の展開 (2018)
  • Author(s): 木須伊織, 阪埜浩司, 的場優介, 青木大輔
  • Organizer: 第43回日本外科系連合学会学術集会
  • Invited
• [Presentation] 子宮移植は新たな臓器移植医療となり得るか？―子宮移植の現況と展望― (2018)
  • Author(s): 木須伊織
  • Organizer: 第14回移植医療教育セミナー
  • Invited
• [Presentation] 非ヒト霊長類動物における世界初の子宮移植後の妊娠 (2018)
  • Author(s): 木須伊織, 加藤容二郎, 尾原秀明, 山田洋平, 松原健太郎, 真杉洋平, 的場優介, 阪埜浩司,青木大輔
  • Organizer: 第54回日本移植学会総会
• [Presentation] 子宮移植は新たな生殖医療になり得るか？ (2018)
  • Author(s): 木須伊織
  • Organizer: 第16回播磨産婦人科内分泌研究会
  • Invited
• [Presentation] 子宮移植の現状について (2017)
  • Author(s): 木須伊織
  • Organizer: 第6回日本子宮移植研究会学術集会・市民公開講座
• [Presentation] 霊長類動物における子宮移植技術の開発～子宮性不妊症に対する新治療の臨床応用に向けて～ (2017)
  • Author(s): 木須伊織
  • Organizer: 第69回日本産科婦人科学会学術集会
• [Presentation] 子宮移植の現状と課題 (2017)
  • Author(s): 子宮移植
  • Organizer: 第9回熊本産婦人科手術学フロンティア学術講演会
  • Invited
• [Presentation] Current status of uterus transplantation research in Japan: towards clinical application (2017)
  • Author(s): Iori Kisu
  • Organizer: The 25th Asian & Oceanic Congress of Obstetrics & Gynaecology
  • Int'l Joint Research
• [Presentation] 子宮移植は可能か？－霊長類動物を用いた基礎実験から臨床応用へ－ (2017)
  • Author(s): 木須伊織
  • Organizer: 第42 日本外科系連合学会学術集会
• [Presentation] 子宮移植に関する最新の知見 (2017)
  • Author(s): 木須伊織
  • Organizer: 第35 日本受精着床学会学術集会
• [Presentation] Uterus transplantation: towards clinical application (2017)
  • Author(s): Iori Kisu
  • Organizer: 第59回日本婦人科腫瘍学会学術講演会
• [Presentation] An undate on recent research findings on uterus transplantation macaque studies. (2017)
  • Author(s): Iori Kisu
  • Organizer: 1st Congress of International Society of Uterus Transplantation
  • Int'l Joint Research / Invited
• [Presentation] 霊長類動物における子宮同種移植手術技術の開発 ～より安定なモデル作製を目指して～ (2017)
  • Author(s): 木須伊織
  • Organizer: 第22回日本生殖内分泌学会学術集会
• [Presentation] 第1回国際子宮移植学会学術報告会：婦人科医療の視点から (2017)
  • Author(s): 木須伊織
  • Organizer: 第7回日本子宮移植研究会学術集会
• [Presentation] Current status of uterus transplantation research in Japan: towards clinical application (2017)
  • Author(s): Kisu I, Banno K, Matoba Y, Adachi M, Aoki D
  • Organizer: The 15th Congress of the Asian Society of Transplantation
  • Int'l Joint Research
• [Book] Chapter 7 Nonhuman Primate Research in Uterus Transplantation (2020)
  • Author(s): Kisu I, Matoba Y, Banno K, Aoki D.
  • Total Pages: 230
  • Publisher: Springer.
• [Book] 実践 臨床生殖免疫学 8. 移植免疫 (3)子宮移植 (2018)
  • Author(s): 木須伊織, 阪埜浩司、青木大輔
  • Total Pages: 730
  • Publisher: 中外医学社