Sugimoto, Shinya

写真a

Affiliation

School of Medicine, Department of Internal Medicine (Gastroenterology and Hepatology) ( Shinanomachi )

Position

Instructor

Academic Background 【 Display / hide 】

  • 2003.04
    -
    2009.03

    Keio University, School of Medicine

    University, Graduated

  • 2014.04
    -
    2018.03

    Keio University, 医学研究科医学研究系専攻

    Graduate School, Completed, Doctoral course

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Academic Degrees 【 Display / hide 】

  • 博士（医学）, Keio University, Coursework, 2018.03

    Reconstruction of the Human Colon Epithelium In Vivo

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Research Areas 【 Display / hide 】

  • Life Science / Gastroenterology

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Research Keywords 【 Display / hide 】

  • オルガノイド

  • 潰瘍性大腸炎関連腫瘍

  • 炎症性腸疾患

  • 短腸症候群

  • 腸管上皮幹細胞

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Books 【 Display / hide 】

  • Organoid derivation and orthotopic xenotransplantation for studying human intestinal stem cell dynamics

    Sugimoto S., Fujii M., Sato T., Methods in Molecular Biology, 2020

    　View Summary

    Intestinal stem cells continuously self-renew throughout life to maintain gut homeostasis. With the advent of the organoid culture system, we are now able to indefinitely expand healthy and diseased tissue-derived human intestinal stem cells in vitro and use them for various applications. Nonetheless, investigating the behavior of human intestinal stem cells in vivo still remains challenging. We recently developed an orthotopic xenotransplantation system that realizes in vivo reconstruction of human intestinal epithelial tissue with preserved stem cell hierarchy by engrafting human normal colon organoids onto the mouse colon surface. We also introduced new growth factors, namely, insulin-like growth factor-1 (IGF-1) and fibroblast growth factor-2 (FGF-2), into the culture condition for human intestinal organoids that significantly increase scalability and transfectability of the organoids. By integrating these recent advances, we organized a tissue-oriented platform encompassing derivation of patient-derived intestinal organoids and their orthotopic xenotransplantation. The research platform based on orthotopic xenotransplantation of human intestinal organoids provides a powerful tool for studying human intestinal stem cell biology in native tissue-relevant contexts as well as for establishing novel disease modeling systems.

  • Establishment of 3D intestinal organoid cultures from intestinal stem cells

    Sugimoto S., Sato T., Methods in Molecular Biology, 2017

    　View Summary

    The intestinal epithelium is the most rapidly renewed tissue in adult mammals, and its renewal is strictly controlled by intestinal stem cells. Extensive studies using genetic models of intestinal epithelium have revealed the mechanisms underlying the self-renewal of intestinal stem cells. Exploiting this knowledge, we developed a novel 3D culture system that enables the outgrowth of intestinal Lgr5+ stem cells derived from mouse and human tissues into ever-expanding crypt–villus mini-guts, known as intestinal epithelial organoids. These organoids are maintained by the self-renewal of stem cells and give rise to all differentiated cell types of the intestinal epithelium. Once established, organoids can be cryopreserved and thawed when needed. This culture system has been widely used for studying stem cell behavior and gene function and for disease modeling.

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Papers 【 Display / hide 】

  • Evaluation of drug-induced lymphocyte stimulation test in mesalazine-associated allergic drug reaction

    Fukasawa N., Kiyohara H., Adachi T., Sugimoto S., Yoshimatsu Y., Murakami S., Mizushima I., Kaieda Y., Takabayashi K., Tsunoda J., Nakamoto N., Fukunaga K., Taguri M., Mikami Y., Kanai T.

    Journal of Allergy and Clinical Immunology Global 5 ( 2 ) 100625 2026.03

    　View Summary

    Background: 5-Aminosalicylic acid (5-ASA) is a fundamental drug for UC management; however, adverse reactions can lead to poor clinical outcomes and increased health care costs. No objective tests currently exist to predict adverse reactions. This study thus investigated 5-ASA across 4 formulations and addressed a key issue in the treatment of mild to moderate ulcerative colitis (UC). Objective: We aimed to examine the utility of the drug-induced lymphocyte stimulation test (DLST) in predicting successful rotation from mesalazine to sulfasalazine (SASP) in patients with UC. Methods: We retrospectively analyzed the largest cohort to date of patients with UC who were suspected of 5-ASA–associated adverse reactions and underwent DLST. We evaluated the DLST positivity rate for the suspected formulation, cross-reactivity to nonsuspected formulations, and clinical outcomes after rotation from mesalazine to SASP. Results: Mesalazine formulations exhibited a DLST positivity rate of 22.0% (18/82), with 45.1% (37/82) of patients testing positive for at least one 5-ASA formulation. Cross-reactivity between mesalazine and SASP was lower at 12.2% (10/82), likely because of structural differences. Adverse reactions typically developed within 2 weeks of initiating 5-ASA and commonly included fever, diarrhea, and bloody stool. Among patients with mesalazine-associated adverse reactions with DLST-negative test result for SASP, 8 of 12 tolerated the rotation. Rotation failure was mainly associated with a positive or borderline DLST result for mesalazine. Conclusions: DLST serves as a useful diagnostic tool for guiding treatment in patients with UC and suspected 5-ASA–associated hypersensitivity reactions. Prospective multicenter studies are needed to validate its clinical utility.

  • Niche-preserving transplantation promotes functional engraftment of intestinal organoids in rat short bowel syndrome

    Endo R., Sugimoto S., Kuwashima Y., Matano M., Hanyu H., Takahashi S., Kato H., Tanaka T., Sihombing A.M., Shirosaki K., Hatano Y., Sugiura Y., Kanai T., Wada M., Sato T.

    Cell Stem Cell 33 ( 1 ) 157 - 165.e6 2026.01

    ISSN  19345909

    　View Summary

    Short bowel syndrome (SBS) is a life-threatening condition in which outcomes often critically depend on ileal function, the only intestinal segment specialized for bile acid uptake and efficient fat absorption. However, whether restoring ileal epithelium-specific nutrient absorption can ameliorate SBS has remained unknown. Here, we demonstrate a niche-preserving transplantation strategy enabling highly efficient engraftment of intestinal organoids into the rat small intestine. Clearing luminal mucus with N-acetylcysteine facilitates ethylenediaminetetraacetic acid (EDTA)-based epithelial detachment, enabling removal of Lgr5<sup>+</sup> stem cells while preserving the stromal niche. This preconditioning increased the engrafted area and enabled the generation of an ilealized jejunum that improved body-weight trajectories and survival in rat SBS. Furthermore, the engrafted epithelia endowed the jejunum with bile acid absorption capacity. These findings provide in vivo evidence for stem cell niche theory, showing that the niche is essential to accommodate donor stem cells, and establish ilealized jejunum as a path toward autologous, region-targeted therapy for SBS.

  • Characterization of Computed Tomography Colonography Findings of Ulcerative Colitis-Associated Neoplasia.

    Kaieda Y, Sugimoto S, Suzuki T, Matsumoto S, Kiyohara H, Takabayashi K, Yoshimatsu Y, Okabayashi K, Shigeta K, Sakakibara R, Wakisaka Y, Murakami S, Jinzaki M, Iwao Y, Mikami Y, Kanai T

    Inflammatory bowel diseases  2025.12

    ISSN  1078-0998

  • Direct reprogramming of mouse fibroblasts into self-renewable alveolar epithelial-like cells

    Morita A., Ishii M., Asakura T., Yotsukura M., Hegab A.E., Kusumoto T., Namkoong H., Ogawa T., Nakatake Y., Oda M., Saito F., Kamata H., Hamamoto J., Okamori S., Ebisudani T., Yasuda H., Sugimoto S., Kuze Y., Seki M., Suzuki Y., Hasegawa N., Asamura H., Watanabe H., Ko M., Sato T., Ieda M., Fukunaga K.

    Npj Regenerative Medicine 10 ( 1 ) 30 2025.12

    　View Summary

    Direct reprogramming is a breakthrough technology that can alter the fate of cells without the passage of stem cells. However, direct reprogramming of somatic cells into pulmonary alveolar epithelial cells has not yet been achieved. Here, we report the direct reprogramming of mouse tail tips and embryonic fibroblasts into induced pulmonary alveolar epithelial-like cells (iPULs) using four transcription factor-coding genes (Nkx2-1, Foxa1, Foxa2, and Gata6) and three-dimensional culture. The iPULs showed lamellar body-like structures and displayed key properties of pulmonary alveolar epithelial cells. Although the potential for iPULs to morphologically differentiate into alveolar epithelial type 1 cells was limited in vitro, the intratracheal administration of iPULs in a bleomycin-induced mouse model of pulmonary fibrosis led to their integration into the alveolar surface, where they formed both alveolar epithelial type 1 and type 2-like cells. Thus, reprogrammed fibroblasts may represent a new source of pulmonary alveolar epithelial cells for regenerative medicine.

  • Understanding the Differentiation Pathway to Bestrophin 4-Positive Cells in Human Colonic Epithelium.

    Wakisaka Y, Sugimoto S, Oda M, Pastuhov S, Fujii M, Sato T, Keio Organoid Consortium

    Gastroenterology 169 ( 1 ) 154 - 157.e5 2025.02

    ISSN  0016-5085

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Reviews, Commentaries, etc. 【 Display / hide 】

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • Visualization of intestinal lesions in vivo by diseased tissue reconstruction

    2024.06
    -
    2026.03

    挑戦的研究（萌芽）, Principal investigator

  • 細胞移植による腸管上皮機能の変換

    2023.04
    -
    2026.03

    文部科学省・日本学術振興会, 科学研究費助成事業, 基盤研究(B), Principal investigator

  • 短腸症候群モデルを用いた新規移植療法の開発

    2021.07
    -
    2023.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Challenging Research (Exploratory), Principal investigator

  • Functional analysis of small intestinal epithelial organoid-based transplant graft

    2020.04
    -
    2023.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Principal investigator

  • 腸管AhRワールドの解明

    2019.02
    -
    2021.03

    文部科学省・日本学術振興会, 科学研究費助成事業, Promotion of Joint International Research (Fostering Joint International Research (B)), Coinvestigator(s)

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Awards 【 Display / hide 】

  • 第60回日本消化器免疫学会総会奨励賞

    2023.10

    Type of Award： Award from Japanese society, conference, symposium, etc.

  • 第31回日本医学会総会奨励賞　内科領域

    2023.04

    Type of Award： Award from Japanese society, conference, symposium, etc.

  • 若手奨励賞

    2022.10, 第30回日本消化器関連学会週間（JDDW 2022 FUKUOKA）

    Type of Award： Award from Japanese society, conference, symposium, etc.

  • 第5回同窓会賞（基礎研究分野 猿田享男賞）

    2022.07, 慶應義塾大学医学部内科学教室

    Type of Award： Keio commendation etc.

  • The 11th JSGE-UEG Rising Stars

    2022.04, The Japanese Society of Gastroenterology - United European Gastroenterology

    Type of Award： Award from international society, conference, symposium, etc.

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Courses Taught 【 Display / hide 】

  • LECTURE SERIES, INTERNAL MEDICINE (GASTROENTEROLOGY)

    2025

  • LECTURE SERIES, INTERNAL MEDICINE (GASTROENTEROLOGY)

    2024

  • LECTURE SERIES, INTERNAL MEDICINE (GASTROENTEROLOGY)

    2023

  • LECTURE SERIES, INTERNAL MEDICINE (GASTROENTEROLOGY)

    2022

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