The development of the treatment for complete remission of IBD using human in vivo model

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22867
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Watanabe Sho 東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (00878100)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 炎症塑性リセット / オルガノイド / ヒト体外モデル / 潰瘍性大腸炎

Outline of Final Research Achievements

Inflammatory bowel disease (IBD) is an intractable disease that once "in remission" is not "cured," but rather relapses, resulting in a prolonged illness period. Even in remission, the intestinal epithelial cells, such as the crypt distortion, have not completely normalized, and ulcer recurrence due to its fragility has long been reported, but its cause is unknown. In this study, we constructed a model and identified specific factors based on comprehensive gene expression analysis in an inflammatory model using human colonic organoids. We succeeded in resetting the inflammatory vulnerability, as cell proliferation was observed even under inflammatory stimuli when these factors were deficient. The expression of the factors was also confirmed in patients with ulcerative colitis, suggesting that they are novel therapeutic targets.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

潰瘍性大腸炎の治療目睫は炎症の抑制から上皮の再生を伴う粘膜治癒に移行しています。しかし、粘膜治癒を達成しても組織学的に異常を認める場合は依然、再燃する危険性があります。組織学的治癒まで達成するメカニズムや治療薬の開発は潰瘍性大腸炎の再燃を予防し、難病から脱却する完全治癒を達成することが期待できることからも社会的意義の高い成果と考えています。