Reconstruction of Liver Tissue In Situ through Dual Injection of Hepatocytes and ECM

2024 Fiscal Year Final Research Report

• Project/Area Number: 22K18186
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 90110:Biomedical engineering-related
• Research Institution: Kyushu University
• Principal Investigator: Shirakigawa Nana 九州大学, 工学研究院, 助教 (90724386)
• Project Period (FY): 2022-04-01 – 2025-03-31
• Keywords: 再生医療 / 肝臓 / 細胞外マトリックス / 肝障害

Outline of Final Research Achievements

This study aimed to develop an alternative to liver transplantation by constructing liver tissue within the native liver using a double injection method involving hepatocytes and liver-derived extracellular matrix (ECM). In the first year, ECM materials capable of gelation in vivo were developed. Mixtures of type I collagen or gelatin with genipin successfully formed stable gels under physiological conditions. In the second year, a liver cirrhosis mouse model was established by drug administration, and hepatocyte/ECM co-injection led to successful cell engraftment. In the third year, cryosections were prepared to evaluate tissue formation. Although transplanted hepatocytes were localized and survived, lobule-like structures were not observed. Further improvement of ECM composition and optimization of the microenvironment are necessary to promote organized tissue development and functional recovery.

Free Research Field

生物化学工学

Academic Significance and Societal Importance of the Research Achievements

本研究は、肝細胞と肝臓由来ECMを同時に注入することで、生体内において機能的な肝組織の構築を試みた点で、再生医療分野に新たなアプローチを提示する学術的意義がある。特に、体内でゲル化可能なECM基材の開発や、肝疾患モデル動物に対する応用は、微小環境の設計による組織再構築の実現性を示す重要な成果である。社会的には、深刻なドナー不足に直面している肝移植医療に対し、より低侵襲で適用可能な再生医療技術の確立は、新たな治療選択肢を提供する可能性があり、将来的な臨床応用に向けた大きな一歩となる。