Reconstruction of liver from arranged-hepatocytes/liver sinusoidal endothelial cells/cholangiocytes tissues

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H04445
• 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: Kyushu University
• Principal Investigator: SAKAI Yusuke 九州大学, 工学研究院, 助教 (10608904)
• Co-Investigator(Kenkyū-buntansha): 江口 晋 長崎大学, 医歯薬学総合研究科(医学系), 教授 (80404218) ; 中澤 浩二 北九州市立大学, 国際環境工学部, 教授 (00304733)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 肝細胞 / 内皮細胞 / 胆管 / 類洞 / 肝再生医療

Outline of Final Research Achievements

Hepatocytes/endothelial cell tissue arranged in a network was prepared using a multi-pored silicone film (MPSF). Rat primary hepatocytes cultured with arranged human umbilical vein endothelial cells (HUVECs) or liver sinusoidal endothelial cells (hLSECs) showed highly expressed liver-specific genes. The tissue maintained its functions subcutaneously in mice, suggesting the reconstruction of capillaries with luminal structure. A method for efficiently producing bile duct tissue from hepatic progenitor cells were established. The junction between bile duct tissue and hepatic bile canaliculus were demonstrated. By combining these techniques, we will establish an innovative method for creating a “liver” with sinusoid and bile duct structures.

Free Research Field

再生医工学

Academic Significance and Societal Importance of the Research Achievements

肝小葉に代表される秩序立った構造と多岐にわたる機能を持つ肝臓の再構築は、困難を極めている。本研究では、初代肝細胞、類洞内皮細胞、胆管細胞を立体配置して“効率的な物質交換を実現する肝細胞／類洞索状構造”と“胆汁排泄を担う胆管”の複合組織を実現する世界初の技術を確立した。再生医療や薬物代謝アッセイ等に有望な肝組織を作製する技術であり、ドナー不足の解消や薬剤代謝予測に繋がることから社会的な意義も大きい。