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2018 Fiscal Year Final Research Report

Development of innovative treatment for liver cancer by elucidation of mechanism of invasion and metastasis liver cancer using miniature human liver

Research Project

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Project/Area Number 16K10586
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionKumamoto University

Principal Investigator

YAMASHITA Youichi  熊本大学, 大学院生命科学研究部(医), 特任准教授 (00404070)

Co-Investigator(Kenkyū-buntansha) 井嶋 博之  九州大学, 工学研究院, 教授 (10274515)
辻田 英司  独立行政法人国立病院機構福岡東医療センター(臨床研究部), 独立行政法人国立病院機構福岡東医療センター臨床研究部, 外科医長 (20389414)
相島 慎一  佐賀大学, 医学部, 教授 (70346774)
白木川 奈菜  九州大学, 工学研究院, 助教 (90724386)
Project Period (FY) 2016-04-01 – 2019-03-31
Keywordsミニチュアヒト肝臓 / 脱細胞鋳型肝臓 / ヒト初代培養肝細胞 / 不死化ヒト肝細胞 / ex vivo還流培養 / 浸潤・転移
Outline of Final Research Achievements

We succeeded in creating a decellularized liver maintaining a fine vasculature by portal vein infusion of Triton X to rat liver. By newly incorporating an artificial lung device into the circulation circuit, ex vivo culture was possible for up to 2 days. A protocol for collection of human primary hepatocytes was established, and a miniature human liver having like a sinusoid structure was created by seeding from the hepatic artery and ex vivo circulation culture. Immortalization of human primary culture hepatocytes was achieved by gene transfer, but the liver specific function was reduced to 1/10. We succeeded in visualizing circulating cancer cells using Keyence system in this circulatory circuit.

Free Research Field

肝胆膵外科

Academic Significance and Societal Importance of the Research Achievements

ミニチュアヒト肝臓の創生と高酸素供給を実現したその還流培養法の確立は、現在培養細胞で代替的に行われている新規薬物の毒性試験へ応用できる可能性がある。また、スケールアップする事で、ヒトの肝臓を創生する事が可能となり、移植グラフトなどへ応用できる可能性がある。初代培養を不死化する事で、スケールアップの際に最も問題となる細胞量の確保を克服できる可能性がある。

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Published: 2020-03-30  

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