Development of an innovative culture system for primary human hepatocytes to proliferate and preserve for a long term in vitro

2022 Fiscal Year Final Research Report

• Project/Area Number: 19H04439
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 90110:Biomedical engineering-related
• Research Institution: The University of Tokyo
• Principal Investigator: Okitsu Teru 東京大学, 医学部附属病院, 届出研究員 (10378672)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 初代肝細胞 / 細胞培養システム / 細胞ファイバ技術 / コアシェルマイクロファイバ

Outline of Final Research Achievements

The purpose of this study is to develop a system that can culture primary human hepatocytes for a long term while maintaining their proliferation and metabolic/secretory capabilities by applying cell fiber technology. We planned the proof of concept would be performed using primary rat hepatocytes, followed by transition to primary human hepatocytes. By optimizing the conditions of initial cell density and the addition of growth factors to the culture medium, we succeeded in letting primary rat hepatocytes proliferate in core-shell microfibers and culturing them for a long period of time while keeping their hepatic capabilities. Subsequently, the potent usefulness of this culture system in the fields of drug discovery and transplant medicine was demonstrated. The experiment using primary human hepatocytes, which was scheduled for the final year of this project, could not be conducted because the deadline for re-commissioning of the research fund had passed due to a miscommunication.

Free Research Field

組織移植医療

Academic Significance and Societal Importance of the Research Achievements

本研究成果の学術的意義は、簡便な培養システムの開発により、肝細胞が、細胞分裂能と代謝・分泌能を維持したまま、長期生存できる環境を生体外に構築できることを実証したことである。また、その社会的意義は、当該培養システムの創薬・移植医療分野への応用可能性を示したことである。肝臓は、生体の恒常性維持に寄与する重要臓器のひとつである。肝臓を構成する主要細胞である肝細胞の機能を生体外で長期間維持できて、かつ、他施設への普及が容易である培養システムの開発は、医学分野での生理・病理の理解にくわえ、医療/創薬分野における治療法/薬剤の開発・標準化に少なからず貢献をすることが期待される。