Tissue Engineering for lower urinary tract using multi-layered mesenchymal stem cell sheets

• Project/Area Number: 17K11177
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Shinshu University
• Principal Investigator: ISHIZUKA OSAMU 信州大学, 学術研究院医学系, 教授 (20184541)
• Co-Investigator(Kenkyū-buntansha): 今村 哲也 信州大学, 学術研究院医学系, 助教 (00467143)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 再生療法 / 骨髄幹細胞 / 膀胱 / 尿道 / 再生医療 / 脂肪幹細胞 / 下部尿路 / 多層細胞シート

Outline of Final Research Achievements

Bone marrow stem cells were taken from the animal femurs. The cells were cultured and proliferated as a cell-sheet. These sheets were piled up to be multi-layered sheets. This sheet was transplanted to cryo-injured bladder or urethra. We could find the morphological regeneration by normal and fluorescence microscope and the functional regeneration by urodynamic study for the bladder and urethra.

Academic Significance and Societal Importance of the Research Achievements

学術な意義としては、骨髄幹細胞は自身の細胞を利用しているため、拒絶反応に対する配慮が不要であること、また、採取しただけの細胞では少量で再生を誘導することは不可能と考えられるため、一定期間、培養することによって増殖させた後に増殖を層状に行い、シート状に増殖させることによって、しかも多層構造を構築することにより、高度な機能をもつ膀胱、尿道などの管腔臓器の再生を試みている点である。また、再生された膀胱・尿道組織が十分な機能を持つかの検証も尿流動態検査を行い、生理的な状態で検証する点は独創的と考えられる。この研究成果は、何らかの理由により、膀胱・尿道機能を喪失した患者に光明を与えるものである。

Research Products

• [Journal Article] Biofabricated structures reconstruct functional urinary bladders in radiation -injured rat (2018)
  • Author(s): Imamura, T., Shimamura, S., Ogawa, T., Minagawa, T., Nagai, T., Silwal Gautam, S., Ishizuka,
  • Journal Title: Tissue Eng. Part A Volume: 24 Issue: 21-22 Pages: 1574-1587
  • DOI: 10.1089/ten.tea.2017.0533
  • Peer Reviewed / Open Access
• [Journal Article] FGF2 Has Distinct Molecular Functions from GDNF in the Mouse Germline Niche (2018)
  • Author(s): Masaki Kaito、Sakai Mizuki、Kuroki Shunsuke、Jo Jun-Ichiro、Hoshina Kazuo、Fujimori Yuki、Oka Kenji、Amano Toshiyasu、Yamanaka Takahiro、Tachibana Makoto、Tabata Yasuhiko、Shiozawa Tanri、Ishizuka Osamu、Hochi Shinichi、Takashima Seiji
  • Journal Title: Stem Cell Reports Volume: 10 Issue: 6 Pages: 1-11
  • DOI: 10.1016/j.stemcr.2018.03.016
  • NAID: 120007037475
  • Peer Reviewed / Open Access
• [Journal Article] Biofabricated structures reconstruct functional urinary bladders in radiation -injured rat bladders. (2018)
  • Author(s): Imamura, T., Shimamura, S., Ogawa, T., Minagawa, T., Nagai, T., Silwal Gautam, S., Ishizuka, O.
  • Journal Title: Tissue Eng. Part A Volume: 印刷中
  • NAID: 120007099780
  • Peer Reviewed
• [Journal Article] Design of a single-arm clinical trial of regenerative therapy by periurethral injection of adipose-derived regenerative cells for male stress urinary incontinence in Japan: the ADRESU study protocol. (2017)
  • Author(s): Shimizu, S., Yamamoto, T., Nakayama, S., Hirakawa, A., Kuwatsuka, Y., Funahashi, Y., Matsuoka, Y., Takanari, K., Toriyama, K., Kamei, Y., Narimoto, K., Yamanishi, T., Ishizuka, O., Mizuno, M., Gotoh, M.
  • Journal Title: BMC Urology Volume: 17 Issue: 1 Pages: 89-95
  • DOI: 10.1186/s12894-017-0282-7
  • Peer Reviewed
• [Journal Article] Implantation of autologous bone marrow-derived cells improve erectile dysfunction in spontaneously hypertensive rats. (2017)
  • Author(s): Ishikawa, M., Imamura, T., Nishizawa, O., Ishizuka,O.
  • Journal Title: Shinshu Medical Journal Volume: 65 Pages: 37-44
  • NAID: 130005397650
  • Peer Reviewed
• [Presentation] Implantation of biofabricated autologous adipose derived cell C-type structures regenerate cryo-injured urethra. (2019)
  • Author(s): Gautam Silwal S, Imamura, T., Shimamura, M., Minagawa, T., Manabu, U., Ogawa, T., Ishizuka, O.
  • Organizer: The 51th Annual Meeting of the International Continence Society
  • Int'l Joint Research
• [Presentation] Biofabricated autologous adipose derived C-type cell structure regenerates cryo-injured urethra in rabbits. (2019)
  • Author(s): Sudha, G.S., Imamura, T., Minagawa, T., Ogawa, T., Ishizuka, O.
  • Organizer: The 14th Pan-pacific continence society annual meeting
  • Int'l Joint Research
• [Presentation] 脂肪由来幹細胞による腎機能再生の評価を目的とした凍結傷害によるラット腎機能障害モデルの作成 (2019)
  • Author(s): 道面尚久、今村哲也、井上貴浩、石塚 修
  • Organizer: 第１０７回日本泌尿器科学会総会
• [Presentation] Biofabricated autologous adipose derived cell structures reconstruct cryo-injured urethra in rabbits (2018)
  • Author(s): Gautam Silwal S, Imamura, T., Shimamura, M., Minagawa, T., Takashi, N., Manabu, U., Nakazawa, M., Ogawa, T., Ishizuka, O.
  • Organizer: The 50th Annual Meeting of the International Continence Society
  • Int'l Joint Research
• [Presentation] Implantation of biofibricated C-type structures composed of autologous adipose derived cells restores cryo-injured urethra in rabbits (2018)
  • Author(s): Sudha, SG, Imamura,T., Shimamura,M., Minagawa,T., Nagai,T., Ueno,M., Saito,T.,Nakazawa, M., Ogawa, T., Isizuka,O.
  • Organizer: 第15回泌尿器科再建再生研究会
• [Presentation] 放射線照射傷害膀胱モデルを用いた骨髄由来細胞立体構造体の移植による膀胱再生． (2018)
  • Author(s): 今村哲也、島村 満、ゴータム・スダ、皆川倫範、永井 崇、小川輝之、石塚 修
  • Organizer: 第15回泌尿器科再建再生研究会
• [Presentation] Implantation of bio-fabricated autologous adipose-derived cell structure into cryo-injured urethra of rabbits. (2018)
  • Author(s): Sudha, S.G., Imamura, T., Shimamura, M., Minagawa, T., Nagai, T., Ueno, M., Saito, T., Nakazawa, M., Ogawa, T., Ishizuka, O.
  • Organizer: 第106回日本泌尿器科学会総会
• [Presentation] 放射線照射傷害膀胱への骨髄由来細胞から作成した立体組織の移植による機能的な膀胱再生． (2018)
  • Author(s): 今村哲也、島村 満、Sudha Gautam、道面尚久、永井 崇、皆川倫範、小川輝之、中沢昌樹、松岡大輔、石塚 修
  • Organizer: 第17回日本再生医療学会総会
• [Presentation] Biofabricated bone marrow-derived cell patches restore structure and function of radiation-injured urinary bladder in rat. (2017)
  • Author(s): Imamura,T., Ogawa,T., Minagawa,T., Nagai,T., Sudha,G., Saito,T., Shimamura,M., Hatakeyama,N., Nakazawa,M., Ishizuka, O.
  • Organizer: American Urological Association Annual Meeting 2017
  • Int'l Joint Research
• [Presentation] 骨髄由来細胞から作製した立体構造体を用いた放射線照射傷害膀胱の機能的な膀胱の再生への試み． (2017)
  • Author(s): 今村哲也、島村 満、皆川倫範、ゴータム・スダ、齊藤徹一、小川輝之、中沢昌樹、石塚 修
  • Organizer: 第14回泌尿器科再建再生研究会
• [Presentation] バイオ３Ｄプリンターで作製した骨髄由来細胞構造体による放射線障害膀胱の機能的な膀胱再生への試み． (2017)
  • Author(s): 今村哲也、島村 満、畠山奈々美、ゴータム スダ、永井 崇、小川輝之、皆川倫範、齊藤徹一、鈴木都史郎、中沢昌樹、石塚 修
  • Organizer: 第16回日本再生医療学会総会