Establishment of refractory inflammatory bowel disease model using human iPS cell-derived self-organizing complex intestinal tissue

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02895
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Mizutani Tomohiro 東京医科歯科大学, 大学院医歯学総合研究科, 講師 (80632588)
• Co-Investigator(Kenkyū-buntansha): 岡本 隆一 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (50451935)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 腸管スフェロイド / iPS細胞 / 腸管グラフト / 自己組織化

Outline of Final Research Achievements

Inflammatory bowel disease is a refractory disease condition with an unknown etiology, and the absence of an ideal experimental model that fully replicates its complex pathology poses a significant challenge so far. This study aimed to create a more physiologically relevant complex intestinal tissue from iPS cell-derived self-organizing intestinal spheroids by co-culturing a diverse other cell populations in a suspension state. The complex multilayered intestinal tissue, derived from iPS cells, demonstrated the ability to form more mature intestinal structure upon xenotransplantation into immunodeficient mice. Based on the findings from this study, the establishment of an in vitro and in vivo experimental system for refractory inflammatory bowel disease could provide deeper insights into the disease's pathology and pave the way for future therapeutic applications.

Free Research Field

消化管再生医療

Academic Significance and Societal Importance of the Research Achievements

本研究によって見いだされた、iPS細胞由来自己組織化複合型腸管スフェロイドは、内胚葉由来の腸上皮細胞と中胚葉由来の間質細胞を有する複合型の腸管組織を作り出した。これは、今までのiPS細胞由来腸オルガノイドが球状構造であったのに対して、腸組織の生理的構造の最大の特徴である管腔構造を再現し得た点において、体外において腸組織が有する複合的な生命現象を解明する実験系としての可能性が強調される。将来的には、全ての細胞種を実装した完全なる腸組織を作出することで、様々な生理および疾患病理を再現しうる体外実験モデルの可能性が期待される。