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Development of an evaluation system for intestinal epithelial disorders in inflammatory bowel disease.

Research Project

Project/Area Number 22K08048
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionUniversity of Tsukuba

Principal Investigator

Kobayashi Mariko  筑波大学, 附属病院, 病院講師 (00932211)

Co-Investigator(Kenkyū-buntansha) 土屋 輝一郎  筑波大学, 医学医療系, 教授 (40376786)
Project Period (FY) 2022-04-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2024: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords炎症性腸疾患 / IBD人工モデル / 上皮障害度
Outline of Research at the Start

炎症性腸疾患(IBD)は寛解と再燃を繰り返す難治性の疾患です。現在の治療目標は炎症を制御し症状を改善させるだけでなく、内視鏡的に潰瘍が消失する粘膜治癒が提唱されています。これは炎症細胞に加えて腸管上皮細胞の修復までが予後と密接に関わることを意味していますが、上皮細胞の障害度を評価するシステムは確立されていません。本研究では、IBD患者検体由来の組織からオルガノイドを樹立し多角的な解析により上皮障害度を評価するシステムを構築することを目的としています。得られる成果により、炎症性疾患に対して上皮細胞の視点から疾患を制御するという新しい概念の創出が期待できます。

Outline of Final Research Achievements

Inflammatory bowel disease (IBD) is a refractory inflammatory bowel disease with repeated remissions and relapses. Current treatment targets not only control inflammation and improve symptoms, but also advocate endoscopic ulcer-free mucosal healing, but no system exists to assess the degree of epithelial cell damage histologically and functionally. The applicants established an artificial model of IBD with human colonic organoids and identified a group of factors involved in IBD epithelial vulnerability. As suppression of the fragility factors promoted epithelial cell proliferation even in an inflammatory environment, they analysed whether epithelial cell fragility is closely related to the disease severity and prognosis of IBD. The results provide the basis for a system to assess the degree of epithelial damage.

Academic Significance and Societal Importance of the Research Achievements

国際的なIBDエキスパートによるコンセンサスにおいても治療目標は粘膜治癒から組織学的治癒まで進むべきと報告されている。IBD研究においては腸内環境全体を視野にした病態解明のために、免疫制御機構、腸内細菌叢との関連解析が主に進められているが、粘膜下の免疫担当細胞と管腔内の腸内細菌のインターフェイスとなる腸管上皮細胞について焦点を当てた研究は未だ少ない。本研究の位置づけとしては、腸管上皮細胞評価システムを構築することにより、炎症評価・腸内細菌評価と統合した腸内環境の全体評価が完成するものである。

Report

(4 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • 2022 Research-status Report
  • Research Products

    (9 results)

All 2024 2023 2022

All Journal Article (9 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 9 results,  Open Access: 4 results)

  • [Journal Article] Efficacy and safety of filgotinib for ulcerative colitis: A real‐world multicenter retrospective study in Japan2024

    • Author(s)
      Akiyama Shintaro、Kobayashi Mariko、et al.
    • Journal Title

      Alimentary Pharmacology & Therapeutics

      Volume: in press Issue: 11 Pages: 1413-1424

    • DOI

      10.1111/apt.17961

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical Usefulness of Hypoxia Imaging Colonoscopy for the Objective Measurement of Ulcerative Colitis Disease Activity2024

    • Author(s)
      Akiyama Shintaro、Sakamoto Taku、Kobayashi Mariko、Matsubara Daisuke、Tsuchiya Kiichiro
    • Journal Title

      Gastrointestinal Endoscopy

      Volume: in press Issue: 6 Pages: 0-0

    • DOI

      10.1016/j.gie.2023.12.035

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Severe cytomegalovirus gastritis due to pembrolizumab-induced agranulocytosis2024

    • Author(s)
      Kobayashi Mariko、Sawafuji Taku、Yamada Takeshi
    • Journal Title

      Gastrointestinal Endoscopy

      Volume: 99 Issue: 2 Pages: 284-286

    • DOI

      10.1016/j.gie.2023.07.037

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] Multicenter propensity score‐matched analysis comparing short <i>versus</i> long cap‐assisted colonoscopy for acute hematochezia2023

    • Author(s)
      Kobayashi Mariko、Tsuchiya Kiichiro、Kaise Mitsuru、Nagata Naoyoshi et al
    • Journal Title

      JGH Open

      Volume: 7 Issue: 7 Pages: 487-496

    • DOI

      10.1002/jgh3.12936

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Organoids transplantation as a new modality to design epithelial signature to create a membrane-protective sulfomucin-enriched segment2023

    • Author(s)
      Watanabe Satoshi、Ogasawara Nobuhiko、Kobayashi Sakurako、Kirino Sakura、Inoue Masami、Hiraguri Yui、Nagata Sayaka、Shimizu Hiromichi、Ito Go、Mizutani Tomohiro、Nemoto Yasuhiro、Tsuchiya Kiichiro、Okamoto Ryuichi、Watanabe Mamoru、Yui Shiro
    • Journal Title

      Journal of Gastroenterology

      Volume: 58 Issue: 4 Pages: 379-393

    • DOI

      10.1007/s00535-023-01959-y

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Nationwide cohort study identifies clinical outcomes of angioectasia in patients with acute hematochezia2022

    • Author(s)
      Kobayashi Mariko、Akiyama Shintaro、Tsuchiya Kiichiro、Kaise Mitsuru、Nagata Naoyoshi
    • Journal Title

      Journal of Gastroenterology

      Volume: 58 Issue: 4 Pages: 367-378

    • DOI

      10.1007/s00535-022-01945-w

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Collagen type I-mediated mechanotransduction controls epithelial cell fate conversion during intestinal inflammation2022

    • Author(s)
      Kobayashi S, Ogasawara N, Watanabe S, Yoneyama Y, Kirino S, Hiraguri Y, Inoue M, Nagata S, Okamoto-Uchida Y, Kofuji S, Shimizu H, Ito G, Mizutani T, Yamauchi S, Kinugasa Y, Kano Y, Nemoto Y, Watanabe M, Tsuchiya K, Nishina H, Okamoto R, Yui S.
    • Journal Title

      Inflammation and Regeneration

      Volume: 42 Issue: 1 Pages: 49-49

    • DOI

      10.1186/s41232-022-00237-3

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Characteristics of inflammatory bowel diseases in patients with concurrent immune-mediated inflammatory diseases2022

    • Author(s)
      Akiyama Shintaro、Fukuda Soma、Steinberg Joshua M、Suzuki Hideo、Tsuchiya Kiichiro
    • Journal Title

      World Journal of Gastroenterology

      Volume: 28 Issue: 25 Pages: 2843-2853

    • DOI

      10.3748/wjg.v28.i25.2843

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prevalence and clinical features of patients with autoimmune pancreatitis and inflammatory bowel disease: A systematic review and meta‐analysis2022

    • Author(s)
      Fukuda Soma、Akiyama Shintaro、Tarakji Ahmad、Hamdeh Shadi、Suzuki Hideo、Tsuchiya Kiichiro
    • Journal Title

      Journal of Gastroenterology and Hepatology

      Volume: 37 Issue: 8 Pages: 1474-1484

    • DOI

      10.1111/jgh.15894

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research

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Published: 2022-04-19   Modified: 2026-01-16  

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