Development of therapeutic modality for liver failure using hepatocyte-based liver organoid transplantation approach
| Project/Area Number |
16K01355
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biomedical engineering/Biomaterial science and engineering
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| Research Institution | Osaka University |
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Principal Investigator |
OHASHI KAZUO 大阪大学, 薬学研究科, 招へい教授 (40364062)
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| Co-Investigator(Kenkyū-buntansha) |
川端 健二 国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 幹細胞制御プロジェクト, プロジェクトリーダー (50356234)
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 肝細胞移植 / 肝不全 / 再生医療 / 組織工学 / 臓器作成 / 肝組織工学 |
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| Outline of Final Research Achievements |
The aim of the present study was to establish a novel approach for liver failure using hepatocyte-based liver micro organoid creation. We have utilized hepatocytes isolated and purified from adult mouse livers. Hepatocytes and non-parenchymal cells were used for liver micro organoidc creation. The organoid was then transplanted into the mouse subcutaneous space, kidney capsule space, omental pauch, or intra-abdominal space and liver functions derived from the implanted organoid were investigated. The investigation revealed that intra-abdominal space is a suitable site for their functional survival. When we transplant the liver micro organic into the mice that subsecuently induced severe acute liver failure, the liver micro organid transplantation was found to provide therapeutic value. From these data, transplantation of hepatocyte-based liver micro organid could be a valuable therapeutic tool for liver failure status.
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| Academic Significance and Societal Importance of the Research Achievements |
肝不全を含む末期肝疾患では、肝臓移植が現存する唯一の治療手段である。臓器移植には、深刻かつおそらく解決され得ないドナー不足の問題、多数の医療関係者の関与が必要なこと、臓器提供における社会的課題などの解決すべき課題が伴っている。これらのことから、新規医療の開発は極めて重要な研究開発テーマである。研究代表者の大橋はこれまでに肝細胞を用いた治療的組織作製において世界初の技術開発を数々行ってきた。本研究では、肝不全という病態に焦点をしぼり、肝細胞を用いた組織体（肝オルガノド）を用いた新しい治療開発が目標である。細胞レベルでの肝臓病治療開発に成功すれば、移植医療とともに医療貢献が極めて大きいものとなる。
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Report
(4 results)
Research Products
(24 results)
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[Journal Article] A simple and useful predictive assay for evaluating the quality of isolated hepatocytes for hepatocyte transplantation2019
Author(s)
Matsumura M, Imura T, Inagaki A, Ogasawara H, Fukuoka K , Fathi I, Miyagi S, Ohashi K, Unno M, Kamei T, Satomi S, Goto M
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Journal Title
Scientific Reports
Volume: 9
Issue: 1
Pages: 6166-6166
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Adult hepatocytes direct liver organogenesis through non-parenchymal cell recruitment in the kidney.2018
Author(s)
Utoh R, Komori J, Kuge H, Tatsumi K, Yamada M, Hirohashi S, Tsutsumi M, Amanuma T, Yoshioka A, Nakajima Y, Wake K, Okano T, Lagasse E, Ohashi K.
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Journal Title
J Hepatol.
Volume: 68
Issue: 4
Pages: 744-753
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] The optimization of short-term hepatocyte preservation prior to transplantation2017
Author(s)
Kengo Fukuoka, Akiko Inagaki, Yasuhiro Nakamura, Muneyuki Matsumura, Satoru Yoshida, Takehiro Imura, Yasuhiro Igarashi, Shigehito Miyagi, Kazuo Ohashi, Shin Enosawa, Takashi Kamei, Michiaki Unno, Noriaki Ohuchi, Susumu Satomi, Masafumi Goto
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Journal Title
Transplantation Direct
Volume: in press
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] The investigation on target matrix of collagenase G for achieving tailor-made islet isolation2016
Author(s)
Satoru Yoshida, Youhei Yamagata, Kanako Nakagawa, Kazuhisa Maeda, Kazutaka Murayama, Kimiko Watanabe, Takehiro Imura, Akiko Inagaki, Yasuhiro Igarashi, Shigehito Miyagi, Kazuo Ohashi, Noriaki Ohuchi, Susumu Satomi, Masafumi Goto
Organizer
26th International Congress of the Transplantation Society
Place of Presentation
Hong Kong
Year and Date
2016-08-18
Related Report
Int'l Joint Research
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