Functional urotherial system reconstruction from transformed epithelial cells under flow and extension stress

• Project/Area Number: 18K09176
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Nagoya City University
• Principal Investigator: Maruyama Tetsuji 名古屋市立大学, 医薬学総合研究院(医学), 教授 (50305546)
• Co-Investigator(Kenkyū-buntansha): 安井 孝周 名古屋市立大学, 医薬学総合研究院(医学), 教授 (40326153) ; 林 祐太郎 名古屋市立大学, 医薬学総合研究院(医学), 教授 (40238134) ; 水野 健太郎 名古屋市立大学, 医薬学総合研究院(医学), 准教授 (70448710) ; 中根 明宏 名古屋市立大学, 医薬学総合研究院(医学), 准教授 (70464568)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: ホローファイバー / 伸展刺激 / 細胞工学 / 上皮間葉誘導 / 再生医療 / KIT陽性細胞 / 尿路上皮細胞 / シェアーストレス / 上皮間葉系誘導 / 間葉系細胞 / 尿路再建 / 平滑筋細胞 / 流れストレス / 中空システム

Outline of Final Research Achievements

With cytoengineering method, we have made urotherial sheet with functional smooth muscle layer showing regular special pattern. These cells were under laminar flow stimulation exerted shear and stretch stress, and/or electrical stimulation using hollow-fiber cell-culture system. In addition, ES cells were used to induce these urotherial and smooth muscle cell to minimize preparing time and effort.

Academic Significance and Societal Importance of the Research Achievements

尿路再建術に際しては、摘除した尿管組織の補填材料として生体適合性のある機能的な組織が必要とされる。しかし、培養細胞を材料とした組織では力学的強度が不十分であり、また臨床応用可能な必要量が確保できないなどの課題があった。ホローファイバー（中空糸）システムを用いて、幹細胞から再生した尿路上皮細胞と平滑筋細胞とを流体下で共培養する手法により、力学的な強度を持つ尿路組織を作製した。さらに電気刺激とサイトカイン刺激により細胞間接着を強化するとともに間質細胞を分化誘導し、自己調節能力を有し蠕動運動が可能な管腔組織は、尿管などさまざま部位での尿路再建手術に臨床応用が可能な生理的な手術材料となる。

Research Products

• [Journal Article] Antireflux endoscopic injection therapy in postpubertal patients via techniques adopted for the dilated ureteral orifice (2021)
  • Author(s): Maruyama T, Mizuno K, Nishio H, Kato T, Hamakawa T, Ikegami Y, Yasui T, Hayashi Y.
  • Journal Title: BMC Urology Volume: 21 Issue: 1 Pages: 70-75
  • DOI: 10.1186/s12894-021-00842-3
  • Peer Reviewed / Open Access
• [Journal Article] Low Serum Inhibin B/Follicle-Stimulating Hormones and Anti-Mullerian Hormone/Follicle-Stimulating Hormones Ratios as Markers of Decreased Germ Cells in Infants with Bilateral Cryptorchidism (2021)
  • Author(s): Kato T, Mizuno K, Matsumoto D, Nishio H, Nakane A, Kurokawa S, Kamisawa H, Maruyama T, Iwatsuki S, Umemoto Y, Yasui T, Hayashi Y
  • Journal Title: J Urology Volume: 207 Issue: 3 Pages: 701-709
  • DOI: 10.1097/ju.0000000000002344
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Disorganization of claudin-11 and dysfunction of the blood-testis barrier during puberty in a cryptorchid rat model (2020)
  • Author(s): Kato Taiki、Mizuno Kentaro、Nishio Hidenori、Moritoki Yoshinobu、Kamisawa Hideyuki、Kurokawa Satoshi、Nakane Akihiro、Maruyama Tetsuji、Ando Ryosuke、Hayashi Yutaro、Yasui Takahiro
  • Journal Title: Andrology Volume: - Issue: 5 Pages: 231-235
  • DOI: 10.1111/andr.12788
  • Peer Reviewed
• [Presentation] Clinical Analysis of the Role of Thyroid Function in the Differentiation Process of Spermatogonial Stem Cells in Cryptorchid Testes. (2021)
  • Author(s): Mizuno K, Nishio H, Matsumoto D, Kato T, Nakane A, Maruyama T, Yasui T, Hayashi Y.
  • Organizer: American Urological Association Annual Meeting
  • Int'l Joint Research
• [Presentation] Low Serum Inhibin B/Follicle Stimulating Hormone and Anti-Mullerian Hormone. (2021)
  • Author(s): Kato T, Mizuno K, Nishio H, Nakane A, Kurokawa Sa, Kamisawa H, Maruyama T, Iwatsuki S, Umemoto Y, Yasui T, Hayashi Y
  • Organizer: American Urological Association Annual Meeting
  • Int'l Joint Research
• [Presentation] Potential role of EEF1A1 and TPT1 genes expressed in the spermatogonial stem cells as a predictive factor of subsequent testicular growth (2020)
  • Author(s): Kentaro Mizuno, Hidenori Nishio, Tetsuji Maruyama et al
  • Organizer: American Urological Association Annual Meeting 2020, Washington, DC(USA)
• [Presentation] Kdm5a activates the protein kinase A signaling pathway in mouse spermatogonial GC-1 cells (2020)
  • Author(s): Hidenori Nishio, Kentaro Mizuo, Tetsuji Maruyama et al
  • Organizer: American Urological Association Annual Meeting 2020, Washington, DC(USA)
• [Presentation] Disorganization of claudin-11 and dysfunction of the blood-testis barrier during puberty in a cryptorchid rat model (2020)
  • Author(s): Taiki Kato, Kentaro Mizuno, Tetsuji Maruyama et al
  • Organizer: American Urological Association Annual Meeting 2020, Washington, DC(USA) (