| Project/Area Number |
21K08598
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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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| Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
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| Research Institution | Nagasaki University |
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Principal Investigator |
Hidaka Masaaki 長崎大学, 医歯薬学総合研究科(医学系), 客員研究員 (10457541)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 肝前駆細胞 / 胆管再生 / 肝再生 / 再生医療 |
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| Outline of Research at the Start |
現在の肝臓再生医療では、肝細胞が産生した胆汁は胆管への排泄経路がなく、肝細胞から胆管への胆汁排泄経路構築が大事な解決すべき問題点となっている。
本研究では、ラットおよびヒト成熟肝細胞からCLiPを用いて、胆管への誘導を図ると同時に、肝細胞から胆管への胆汁排泄経路構築を行う。ヒトCLiPから肝と胆管細胞との融合により胆汁排泄経路を備えた肝組織移植が可能となれば、肝再生医療における１つの大きな問題点が解決され、再生医療の一歩を進めることができ得る。
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| Outline of Final Research Achievements |
Liver disease imposes a significant medical burden due to a shortage of liver transplant donors and irreversible progression of liver disease. The aim of this study was to create hepatobiliary tissue organoids (HBOs) and cure liver disease. Hepatic progenitor cells (hCLiPs) were induced using human hepatocytes isolated from cirrhosis using three small molecule compounds. From those progenitor cells, they were successfully induced into bile ducts and mature hepatocytes, exhibited bile secretion and transport functions, and created organoids with both structures. It showed gene expression patterns in both bile ducts and hepatocytes. Functional patient-specific HBOs were also successfully produced from hCLiPs from cirrhotic liver tissue. Hepatobiliary tissue organoids with bile ducts in the tissue were established from human cirrhotic liver.
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| Academic Significance and Societal Importance of the Research Achievements |
肝移植ドナーの不足と肝疾患の進行により、肝硬変、肝不全診療では依然として大きな医療負担を強いている。肝胆膵オルガノイド（HBO）は、試験管内ミニ臓器モデルを提供し、再生医療の発展に役立つ可能性がある。本研究により、ヒトHBOは、肝胆道系疾患の研究、創薬、個別化医療のための効率的なモデルとしての可能性が示された。
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