Human urethra-engineered with human adipose stem cells with maturation by rearrangement of cells for self-organization - Newly developed scaffold-free three-dimensional bio-printer

• Project/Area Number: 17K11181
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Nagoya University
• Principal Investigator: Tokunori Yamamoto 名古屋大学, 医学系研究科, 特任教授 (20182636)
• 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: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 3Dバイオプリンター / 集塊 / 脂肪幹細胞 / 培養 / 尿道再建 / 集 塊 培養 / 尿道再生 / 集塊 培養 / ３Dプリンター

Outline of Final Research Achievements

We developed newly developed scaffold-free three-dimensional bio-printer by Nakayama　K(JP 2009-509335). Cell aggregatesby human adipose stem　cells (h-ASCs) called “spheroids” are conditioned into three-dimensional macroscopic structures without the need for any scaffold. By adjusting needles length and quantity researchers could change the thickness of urethra from h-MSC(step1:loading, 2:3D printing,3: maturation by rearrangement of cells for self-organization, 3: shear stress). The histologic staining showed that two layers of cells developed in the h-urethra with tention force for the nuds rat and extention with dilation. The urethra showed two layer and human nucli pathologically. The supemanent of urethra revealed 20 cytokaines with regeneration. We succeeded production of an urethra-like structure made of h-ASCs using 3D bio printer and the transplant of it to a nude rat.

Academic Significance and Societal Importance of the Research Achievements

腎で生成された尿は腎盂から尿管を経て膀胱に畜尿され、さらに尿道を経て体外に排尿される。この経路を尿路と言う。健常な膀胱の機能は１）畜尿機能（普段は尿を失禁することなく安定して貯めることができる。）と２）排尿機能（充満時には尿意に基づいて自分の意志で残尿なく排出することができる。）がともに 両立することが求められる。 尿道は排尿機能の体外への排出の重要な役割を果たす。下部尿路再建術において十分再建ができないような症例（先天性尿道下裂(出生１名/300名)、難治性尿道狭窄、尿道膀胱全摘術後）の治療に対してこの技術は有効で社会的意義は高い。

Research Products

• [Journal Article] Tensor-cut: A tensor-based graph-cut blood vessel segmentation method and its application to renal artery segmentation. (2019)
  • Author(s): Wang C, Oda M, Hayashi Y, Yoshino Y, Yamamoto T, Frangi AF, Mori K
  • Journal Title: Med Image Anal. Volume: 1（60） Pages: 101623-101623
  • DOI: 10.1016/j.jpra.2019.01.003
  • Peer Reviewed
• [Journal Article] Precise estimation of renal vascular dominant regions using spatially aware fully convolutional networks, tensor-cut and Voronoi diagrams (2019)
  • Author(s): Chenglong Wang, Holger R. Roth, Takayuki Kitasaka, Masahiro Oda, Yuichiro Hayashi, Yasushi Yoshino, Tokunori Yamamoto, Naoto Sassa, Momokazu Goto, Kensaku Mori
  • Journal Title: Computerized Medical Imaging and Graphics Volume: 77 Pages: 1-13
  • DOI: 10.1016/j.compmedimag.2019.101642
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The influence of the presence of intraductal carcinoma of the prostate on the grade group system's prognostic performance (2019)
  • Author(s): Kato M, Hirakawa A, Kobayashi Y, Yamamoto A, Ishida R,Kamihira O, Kimura T, Majima T, Ishida S, Funahashi Y,Sassa N, Fujita T,Matsukawa Y, Yamamoto T,Hattori R,Gotoh M,Tsuzuki T
  • Journal Title: Prostate Volume: 79(10) Issue: 10 Pages: 1065-1070
  • DOI: 10.1002/pros.23818
  • NAID: 120006725320
  • Peer Reviewed
• [Journal Article] Investigation of the relationship between bladder function and sarcopenia using pressure flow studies in elderly male patients (2019)
  • Author(s): Majima T, Funahashi Y, Matsukawa Y, Inoue S, Sassa N, Kato M, Yamamoto T, Gotoh M
  • Journal Title: Neurourology and Urodynamics Volume: 38(5) Issue: 5 Pages: 1417-1422
  • DOI: 10.1002/nau.24001
  • Peer Reviewed
• [Journal Article] Urodynamic analysis of the sequential impact of diabetes mellitus on bladder function (2019)
  • Author(s): Majimat T, Matskawa Y, Funahashi Y, Takai S, Kato M, Yamamoto T, Gotoh M
  • Journal Title: Int J Urol Volume: 26(6) Issue: 6 Pages: 618-622
  • DOI: 10.1111/iju.13935
  • Peer Reviewed
• [Journal Article] Comparison in the efficacy of fesoterodine or mirabegron add-on therapy to silodosin for patients with benign prostatic hyperplasia complicated by overactive bladder (2019)
  • Author(s): Matsukawa Y, Takai S, Majima T, Funahashi Y, Sassa N, Kato M, Yamamoto T, Gotoh M
  • Journal Title: A randomized, prospective trial using urodynamic studies.Neurourol Urodyn Volume: - Issue: 3 Pages: 941-949
  • DOI: 10.1002/nau.23935
  • Peer Reviewed
• [Journal Article] Pre-treatment serum testosterone level can be a useful factor to predict the improvement in bladder outlet obstruction by tadalafil for male patients with lower urinary tract symptoms induced by benign prostatic obstruction (2019)
  • Author(s): Mastukawa Y, Kanada Y, Takai S, Inoue S, Majima T, Funahashi Y, Kato M, Yamamoto T, Gotoh M
  • Journal Title: Aging Male Volume: 16 Issue: 5 Pages: 1-7
  • DOI: 10.1080/13685538.2018.1563777
  • Peer Reviewed
• [Journal Article] Long-term efficacy and safety of regenerative treatment for male stress urinary incontinence using autologous adipose-derived regenerative cells (2019)
  • Author(s): Gotoh M,Yamamoto T, Shimizu S, Mastukawa Y, Kato M, Majima T, Takai S, Funahashi Y, Toriyama K
  • Journal Title: Int J Urol Volume: 26(3) Pages: 400-405
  • Peer Reviewed
• [Journal Article] Comparison of trophic factors secreted from human adipose-derived stromal vascular fraction with those from adipose-derived stromal/stem cells in the same individuals (2018)
  • Author(s): Hirose Y, Funahashi Y, Matsukawa Y, Majima T, Yamaguchi M, Kawabata S, Gotoh M, Yamamoto T
  • Journal Title: Cytotherapy Volume: 20 Issue: 4 Pages: 589-591
  • DOI: 10.1016/j.jcyt.2018.02.001
  • Peer Reviewed / Open Access / Int'l Joint Research