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

Research Project

Project/Area Number 22K20851
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0902:General internal medicine and related fields
Research InstitutionTokyo 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
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords炎症性腸疾患 / 潰瘍性大腸炎 / クローン病
Outline of Research at the Start

炎症性腸疾患は消化管に慢性炎症を起こす難病で、寛解と再燃を繰り返すことが特徴である。研究代表者らは、新規2次元培養モデルを開発し、マウス大腸上皮の「傷害→再生→治癒」過程をin vitroで再現することに成功し、再生過程で重要な役割を担う遺伝子発現変化を報告した。本研究では、この技術を患者由来ヒト細胞に応用し、炎症性腸疾患患者の上皮で繰り返されるの「傷害→再生→治癒」過程の全貌の解明を目指す。

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.

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。

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (2 results)

All 2024 Other

All Int'l Joint Research (1 results) Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Open Access: 1 results)

  • [Int'l Joint Research] Cleveland Clinic/Washington University in St Louis(米国)

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Long-Term Monolayer Cultivation Captures Homeostatic and Regenerative Features of Human Colonic Epithelial Cells2024

    • Author(s)
      Satoru Fujii, Yi Wang, Shanshan Meng, Ryan J. Musich, Scott T. Espenschied, Kevin Newhall, Yi Han, Shuhei Sekiguchi, Ryoma Matsumoto, Matthew A. Ciorba, L. David Sibley, Ryuichi Okamoto, Thaddeus S. Stappenbeck
    • Journal Title

      bioRxiv

      Volume: -

    • DOI

      10.1101/2024.01.01.573838

    • Related Report
      2023 Annual Research Report
    • Open Access / Int'l Joint Research

URL: 

Published: 2022-09-01   Modified: 2025-01-30  

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