The elucidation of homeostasis regulated by intestinal epithelial stem cells

2018 Fiscal Year Final Research Report

• Project/Area Number: 26221307
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Watanabe Mamoru 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (10175127)
• Co-Investigator(Kenkyū-buntansha): 土屋 輝一郎 東京医科歯科大学, 医学部附属病院, 准教授 (40376786) ; 中村 哲也 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座教授 (70265809)
• Project Period (FY): 2014-05-30 – 2019-03-31
• Keywords: 腸内環境 / 共培養 / 幹細胞機能評価 / 疑似モデル構築 / 全身制御

Outline of Final Research Achievements

Intestinal mucosa is always activated so that all epithelial cells are replaced in approximately one week. Intestinal stem cells supply intestinal epithelial cells to keep normal mucosa by orderly differentiation system. When the control collapses, it becomes the ulcer, resulting in bleeding and infection. Especially, intractable ulceration is often shown in the patients with inflammatory bowel disease (IBD) whose number are increased in Japan. The treatment for the ulcer has however not been established. In this study, our original culturing system of human intestinal epithelial cells as organoids led to clarify the molecular mechanisms for stem cell dysfunction under chronic inflammation and for stem cell regeneration against inflammation. These results might be useful for the development of novel drugs targeting mucosal healing in IBD.

Free Research Field

消化器病学

Academic Significance and Societal Importance of the Research Achievements

腸の細胞を体外で安定し培養することは、様々な環境を再現したモデルを簡単に作成することができます。今回は慢性炎症や再生粘膜を試験管内で再現させることで、幹細胞の機能を解析し、病気の原因や再生の仕組みを明らかにしています。これらの成果は今後炎症性腸疾患に対する新しい治療薬の開発に結びつくことが期待されます。