Development of the transplantable artificial liver using iPS cells and decellularized liver
| Project/Area Number |
16H05489
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatric surgery
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
河合 隆之 京都大学, 医学研究科, 客員研究員 (00813867)
上本 伸二 京都大学, 医学研究科, 教授 (40252449)
石井 隆道 京都大学, 医学研究科, 特定病院助教 (70456789)
福光 剣 京都大学, 医学研究科, 特定病院助教 (70700516)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2016: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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| Keywords | 臓器作製 / 幹細胞生物学 / 再生医療 / 多能性幹細胞 / 人工肝臓 / 肝移植 / 組織工学 / 肝臓移植 / ヒトiPS細胞 / 人工臓器 / 再生医学 / iPS細胞 / 脱細胞化肝臓 |
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| Outline of Final Research Achievements |
We produced a transplantable bio-artificial liver using the decellularized tissue derived from rat native liver. First, we established a protocol and evaluation system such as cell engraftment method and culture method for decellularized tissue of liver and primary culture cells. Next, the basic structure of the liver was reproduced using hepatocyte-like cells differentiated from human iPS cells, and the fundamental hepatocyte function was evaluated. Moreover, not only in the liver but also in the small intestine, a transplantable artificial small intestine was developed using the same method. When decellularized tissue of the rat small intestine was used at the defect site of the small intestine, regeneration of the small intestine wall was observed with the decellularized tissue as a scaffold.
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| Academic Significance and Societal Importance of the Research Achievements |
移植医療において、ドナー不足は深刻な課題である。様々な代替医療の研究が進む中、移植可能な人工肝臓の作製は、課題を解決する方法として、最も理想的な手段であるが実現には多くの困難を伴う方法でもある。脱細胞化組織や自己の組織から作製するiPS細胞を用いることで、移植可能でかつ拒絶反応のない理想的な臓器を作製することが理論的に可能となる。今回、ヒトiPS細胞から肝細胞様細胞へ分化誘導した後に脱細胞化組織の中で培養し、肝臓組織の一部の組織構造や機能を再現したことを示した。今後は、肝不全の患者を救命できるだけの十分な機能と組織構造を有する肝臓を作製できるよう、さらなる技術開発が期待される。
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Report
(4 results)
Research Products
(26 results)
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[Journal Article] Novel hybrid three-dimensional artificial liver using human induced pluripotent stem cells and a rat decellularized liver scaffold2019
Author(s)
Takahito Minami, Takamichi Ishii, Kentaro Yasuchika, Ken Fukumitsu, Satoshi Ogiso, Yuya Miyauchi, Hidenobu Kojima, Takayuki Kawai, Ryoya Yamaoka, Yu Oshima, Hiroshi Kawamoto, Maki Kotaka, Katsutaro Yasuda, Kenji Osafune, Shinji Uemoto
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Journal Title
Regenerative therapy
Volume: 10
Pages: 127-133
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Presentation] A novel culture system preserving natural scaffolds of fibrotic livers accelerates progression of hepatocellular carcinoma cells2018
Author(s)
Yuya Miyauchi, Kentaro Yasuchika Yu Oshima, Hiroshi Kawamoto, Takahito Minami, Hidenobu Kojima, Ryoya Yamaoka, Takayuki Kawai, Satoshi Ogiso, Ken Fukumitsu, Takamichi Ishii, Shinji Uemoto
Organizer
The Asian Pacific Association for the Study of the Liver Single topic Conference on HCC
Related Report
Invited
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[Presentation] A novel three-dimensional culture system, decellularized-tissue obtained from cirrhotic livers, enhances an epithelial-mesenchymal transition phenotype in HCC cells2017
Author(s)
Yuya Miyauchi, Kentaro Yasuchika, Ken Fukumitsu, Satoshi Ogiso, Hidenobu Kojima, Ryoya Yamaoka, Takayuki Kawai, Hokahiro Katayama, Elena Y Yoshitoshi, Sadahiko Kita, Katsutaro Yasuda, Naoya Sasaki, Takamichi Ishii, Junji Komori, Shinji Uemoto
Organizer
American college of Surgeons clinical congress
Related Report
Invited
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[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
Related Report
Int'l Joint Research
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[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
Related Report
Int'l Joint Research
