A novel approach to liver diseases through regenerative strategy.

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20945
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0905:Surgery of the organs maintaining homeostasis and related fields
• Research Institution: Nagasaki University
• Principal Investigator: Tetsuo Hanako 長崎大学, 病院(医学系), 医員 (90966847)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: Hepato-Biliary Sheet / CLiP / 肝細胞シート / 再生医療 / 胆道構造

Outline of Final Research Achievements

Hepatobiliary sheets (HBS) were prepared by culturing CLiP in bile duct induction medium for 14 days, inducing biliary structures, and seeding mature hepatocytes. Immunostaining showed that the bile duct structures and mature hepatocytes were adjacent to each other, and the HBS functioned well in the bile excretion assay. In addition, CYP3A4 activity and albumin production capacity were significantly higher than those of HS. Gene expression of liver-specific enzymes and transporters was significantly higher. In vivo, bile duct structures and vascular components were seen in the sheets. Blood rat albumin levels were significantly higher in the HBS group from 7 to 28 days postoperatively.

Free Research Field

消化器外科再生医療

Academic Significance and Societal Importance of the Research Achievements

これまで細胞源が豊富で培養法が確立した肝細胞を用いた肝臓の再生医療に関しては様々な研究がなされてきたが、胆管上皮細胞は培養困難と言われており、同細胞を細胞源とした胆道系の作製は困難とされてきました。今回、低分子化合物刺激により誘導した肝前駆細胞を用いることで胆管上皮細胞を誘導でき、それにより胆道構造を新たに作製しました。胆道構造を有する肝細胞シートは、肝臓により近い高次元の組織として機能することが期待できます。