Development of novel therapies for biliary atresia using bile duct organoids

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16406
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Juntendo University
• Principal Investigator: Suda Kazuto 順天堂大学, 医学部, 准教授 (60784725)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 胆道閉鎖症 / 肝線維化 / 総胆管結紮 / ラット / 胆管オルガノイド / 脾臓注入モデル

Outline of Final Research Achievements

Biliary atresia is a devastating infantile cholangiopathy due to obstruction of the intrahepatic bile duct and can be treated with portoenterostomy. However, a liver transplant is required in some patients due to prolonged postoperative jaundice. As there is a shortage of liver transplant donors, the development of new treatment is required to improve liver function reserve. This study was designed to establish the organoid culture from the differentiated bile duct epithelium, and to determine the therapeutic effect of splenic inoculation of these organoid cells in the rat model of obstructive jaundice induced by ligation of the common bile duct. So far, successful isolation of the bile duct epithelium with a high quantity and viability has been achieved. We also evaluated biochemical and histological characteristics of the common bile duct ligation model of mouse and rat. On the other hand, we have not achieved the establishment of a stably culturing system for organoid cells.

Free Research Field

小児外科

Academic Significance and Societal Importance of the Research Achievements

本研究は、閉塞性黄疸モデルラットの脾臓に胆管上皮ラット由来オルガノイド細胞を移植して、肝組織内への定着および肝機能改善効果を検証する目的で進められた。予備検討としてのマウスや、ラットの閉塞性黄疸モデル作成は予定通り行えた。これによるコントロールとしての病的意義は示せたものの、胆管上皮オルガノイドの安定した培養系確立に難渋したため、移植実験の施行やその効果判定まで検証できていない。今後、培養系のプロトコルを変更して再試行する予定とし、本研究による治療効果としての学術的意義を見出せるよう計画を継続していく。