The investigation for the establishment of organ processing available for transplantation using 3-dimensional scaffold derived from natural liver

• Project/Area Number: 15K15065
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Kyoto University
• Principal Investigator: Yasuchika Kentaro 京都大学, 医学研究科, 研究員 (00378895)
• Co-Investigator(Kenkyū-buntansha): 上本 伸二 京都大学, 医学研究科, 教授 (40252449)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 再生医療 / 肝臓移植 / 組織工学 / 人工肝臓 / 再生医学 / 胎仔肝前駆細胞 / 脱細胞化肝臓 / 再細胞化

Outline of Final Research Achievements

We can get 3-dimmensional liver scaffold (decellularised liver) from rat normal liver after chemical treatment. The ideal protocol for recellularisation of mouse fetal hepatic progenitor cells and adult hepatocytes to decellularised liver was investigated. Bile duct was revealed to be the ideal route for recellularisation compared to portal vein because of the anatomical features. Furthermore, it was revealed that rat liver sinusoidal endothelial cells (LSEC) inoculated via portal vein were integrated into the decellularised liver scaffold with hepatocytes inoculated via bile duct, and deteriorated the thrombus formation after blood circulation. In addition, we successfully decellularised the cirrhotic liver and investigated the interaction of cirrhotic liver to hepatocellular carcinoma cells.

Research Products

• [Journal Article] Efficient recellularisation of decellularised whole-liver grafts using biliary tree and foetal hepatocytes (2016)
  • Author(s): Ogiso S, et.al.
  • Journal Title: Sci Rep. Volume: 21 Issue: 1 Pages: 35887-35887
  • DOI: 10.1038/srep35887
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Liver sinusoidal endothelial cell as a cell source to fabricate vasculature and maintain performance of hepatocyte in engineered liver graft (2016)
  • Author(s): Hidenobu Kojima, Kentaro Yasuchika, Ken Fukumitsu, Satoshi Ogiso, Yuya Miyauchi, Ryoya Yamaoka, Takayuki Kawai, Hokahiro Katayama, Elena Y Yoshitoshi, Sadahiko Kita, Katsutaro Yasuda, Naoya Sasaki, Takamichi Ishii, Junji Komori, Shinji Uemoto
  • Organizer: he Liver Meeting 2016. American Association for the Study of Liver Disease
  • Place of Presentation: Boston, MA, USA
  • Year and Date: 2016-11-11
  • Int'l Joint Research
• [Presentation] Optimizing recellularization of decellularized whole-liver graft: from which route and with which cell? (2016)
  • Author(s): Satoshi Ogiso, Kentaro Yasuchika, Ken Fukumitsu, Takamichi Ishii, Hidenobu Kojima, Yuya Miyauchi, Ryoya Yamaoka, Hokahiro Katayama, Takayuki Kawai, Sadahiko Kita, Shinji Uemoto
  • Organizer: The American College of Surgeons 102nd Clinical Congress
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2016-10-19
  • Int'l Joint Research
• [Presentation] Biliary tree as a window for repopulation of the decellularized liver scaffold. (2016)
  • Author(s): Satoshi Ogiso, Kentaro Yasuchika, Ken Fukumitsu, Takamichi Ishii, Hidenobu Kojima, Yuya Miyauchi, Ryoya Yamaoka, Hokahiro Katayama, Takayuki Kawai, Elena Yukie Yoshitoshi, Sadahiko Kita, Katsutaro Yasuda, Shinji Uemoto
  • Organizer: 26th International congress of the transplantation society
  • Place of Presentation: Hong Kong
  • Year and Date: 2016-08-20
  • Int'l Joint Research
• [Presentation] 胆管経路の選択による脱細胞化肝臓の効率的な再細胞化 (2016)
  • Author(s): 小木曽聡、安近健太郎、福光剣、小島秀信、宮内雄也、山岡竜也、片山外大、河合隆之、吉利エレーナ、喜多貞彦、安田勝太郎、上本伸二
  • Organizer: 第15回日本再生医療学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2016-03-17
• [Presentation] 脱細胞化組織を鋳型としマウス胎仔肝細胞を細胞源とした三次元肝臓の構築 (2015)
  • Author(s): 小木曽聡、福光剣、安近健太郎、小森淳二、片山外大、河合隆之、喜多貞彦、安田勝太郎、吉利エレーナ、上本伸二
  • Organizer: 第70回日本消化器外科学会総会
  • Place of Presentation: 浜松
  • Year and Date: 2015-07-15
• [Presentation] 脱細胞化骨格を鋳型とし肝前駆細胞を細胞源とした人工肝臓の構築 (2015)
  • Author(s): 小木曽聡、安近健太郎、福光剣、小島秀信、宮内雄也、山岡竜也、片山外大、河合隆之、吉利エレーナ、喜多貞彦、安田勝太郎、上本伸二
  • Organizer: 第27回日本肝胆膵外科学会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2015-06-11
• [Presentation] 脱細胞化組織を鋳型とし胎仔肝細胞を細胞源として用いた三次元人工肝臓の構築 (2015)
  • Author(s): 小木曽聡、安近健太郎、福光剣、小島秀信、宮内雄也、山岡竜也、片山外大、河合隆之、吉利エレーナ、喜多貞彦、安田勝太郎、上本伸二
  • Organizer: 第51回日本肝臓学会総会
  • Place of Presentation: 熊本
  • Year and Date: 2015-05-21
• [Presentation] Fetal hepatocyte as a cell source of liver tissue engineering using a decellularized matrix (2015)
  • Author(s): Satoshi Ogiso、Kentaro Yasuchika, Ken Fukumitsu, Hidenobu Kojima, Yuya Miyauchi, Ryuya Yamaoka, Hokahiro Katayama, Takayuki Kawai, Elena Yoshitoshi, Sadahiko Kita, Katsutaro Yasuda, Shinji Uemoto
  • Organizer: The 50th international liver congress 2015, European Association for the Study of the Liver
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2015-04-22
  • Int'l Joint Research