Investigating Human Intestinal Epithelial Regeneration with a Novel 2D Culture Model

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20851
• 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: Fujii Satoru 東京医科歯科大学, 大学院医歯学総合研究科, プロジェクト助教 (00964751)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 炎症性腸疾患

Outline of Final Research Achievements

We established an air-liquid interface (ALI) culture method for patient-derived human colonic epithelial cells by adapting a technique originally developed for mouse colonic epithelial cells. Through optimization of the culture medium, we identified conditions that can replicate the columnar epithelium characteristic of normal human colonic epithelial cells. At the start of ALI culture, the cells exhibited a flattened morphology, similar to the flattened epithelial cells frequently observed in inflamed regions of ulcerative colitis. Furthermore, we confirmed that the gene expression patterns of these flattened cultured cells were comparable to those of inflamed colonic epithelium in ulcerative colitis and fetal intestinal mucosa.Further application of this culture system holds promise to expand our understanding of the pathogenesis of inflammatory bowel disease and to develop new therapeutic approaches.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

腸上皮細胞の3次元培養法が初めて報告されて以降、3次元培養法は腸上皮細胞の生理機能や腸疾患の病態の解明、および新規治療薬の開発等に大きな貢献をしてきた。しかし、従来の3次元培養法では炎症性腸疾患で繰り返される「傷害→再生→治癒」過程を再現することは困難であった。それに対し、我々が開発した2次元培養モデルは、ヒト腸粘膜の「傷害→再生→治癒」過程を再現し、その過程を経時的に解析することも可能である。よって、この培養モデルをさらに応用することで、ヒト腸上皮の再生メカニズムの解明が期待されるだけでなく、炎症性腸疾患の病態解明、新規診断法や治療法の開発等にも貢献できると期待される。