Development and analysis of small intestinal disease model using small intestinal stem cells

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08964
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: The University of Tokyo
• Principal Investigator: YAMADA ATSUO 東京大学, 医学部附属病院, 助教 (80534932)
• Co-Investigator(Kenkyū-buntansha): 平田 喜裕 東京大学, 医科学研究所, 准教授 (10529192)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 小腸 / 癌 / 粘膜障害 / 薬剤 / 幹細胞

Outline of Final Research Achievements

To model small intestinal diseases, we used SIAC1 cells, which we have established from small intestinal adenocarcinoma, and mouse small intestine as sources of organoids. Organoids from SIAC1 cells proliferated independent of growth factors, such as EGF and Rspo1, which were indispensable for the growth and maintenance of mouse small intestinal organoids. Notch inhibitors increased differentiation marker expression in SIAC1 organoids, while cetuximab or bevacizumab, molecular targeting drugs against colorectal cancer, failed to inhibit SIAC1 xenograft growth. In mouse organoids, E-cadherin was indispensable for normal proliferation, as the conditional deletion of cdh1 gene in organoids disrupted the crypt-like structure. These results suggest the therapeutic potential of differentiation induction or adhesion inhibition against small intestinal adenocarcinoma.

Free Research Field

小腸疾患