杉本　真也 （スギモト　シンヤ）

Sugimoto, Shinya

写真a

所属（所属キャンパス）

医学部 内科学教室（消化器） （信濃町）

職名

助教（有期）
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学歴 【 表示 ／ 非表示 】

  • 2003年04月
    -
    2009年03月

    慶應義塾大学, 医学部

    大学, 卒業

  • 2014年04月
    -
    2018年03月

    慶應義塾大学, 医学研究科医学研究系専攻

    大学院, 修了, 博士

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  • 博士（医学）, 慶應義塾大学, 課程, 2018年03月

    Reconstruction of the Human Colon Epithelium In Vivo

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研究分野 【 表示 ／ 非表示 】

  • ライフサイエンス / 消化器内科学

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研究キーワード 【 表示 ／ 非表示 】

  • 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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著書 【 表示 ／ 非表示 】

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

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

    　概要を見る

    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年

    　概要を見る

    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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  • 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年12月

    　概要を見る

    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 2025年02月

    ISSN  0016-5085

  • First-line biologics as a treatment for ulcerative colitis: a multicenter randomized control study.

    Naganuma M, Shiga H, Shimoda M, Matsuura M, Takenaka K, Fujii T, Yamamoto S, Matsubayashi M, Kobayashi T, Aoyama N, Saito D, Yokoyama K, Moriya K, Tsuchiya K, Shibui S, Kawamoto A, Shimizu H, Okamoto R, Sakamoto K, Yaguchi K, Kunisaki R, Akiyama S, Hayashi R, Hasui K, Kanmura S, Bamba S, Mishima Y, Kakimoto K, Sugimoto S, Nakazawa A, Abe T, Ogata H, Hisamatsu T, Collaborators of the Study

    Journal of gastroenterology 60 （ 4 ） 430 - 441 2025年01月

    ISSN  0944-1174

    　概要を見る

    Background: Despite the availability of several biologics for ulcerative colitis (UC), there remains a critical need to identify first-line treatment biologics. The superiority of infliximab (IFX) over vedolizumab (VED) and ustekinumab (UST) was evaluated as initial UC treatments in patients with biologic-naïve UC. Methods: This multicenter, randomized control trial was conducted across 20 Japanese medical institutions. An independent center randomly allocated patients with UC (Mayo score ≥ 6) who had not previously used biologics to three treatment groups (IFX, VED, UST). The primary endpoint was the clinical remission (CR) rate at week 12, with other endpoints including the treatment continuation rate at week 26 and adverse events (AEs). Results: From May 2021 to June 2023, 107 cases were registered, including 104 for safety and 97 for efficacy evaluation. CR rate at week 12 was 36.4% (95%CI:20.4–54.9), 32.4% (95%CI:17.4–50.5) and 43.3% (95%CI:25.5–62.6) in IFX, VED, and UST group, respectively. Continuation rates at week 26 were 50.0%(IFX), 58.3% (VED), and 82.4% (UST). AEs related to study medication were 14.7% (IFX), 16.7% (VED), and 5.9% (UST). Predictors for CR at week 12 were thiopurine use in IFX (p = 0.04), lower baseline Mayo score (p = 0.007), and lower Patient report outcome 2 (p = 0.003) at week 2 in VED. Conclusion: Due to small sample size, it is challenging to make conclusions for main endpoints from this study while our study suggested that use of thiopurines in IFX group and lower activity at enrollment in VED group may enhance treatment efficacy. (jRCT1031200329; available at https://jrct.niph.go.jp/).

  • Leucine-rich alpha-2 glycoprotein in combination with C-reactive protein for predicting endoscopic activity in Crohn’s disease: a single-centre, cross-sectional study

    Takada Y., Kiyohara H., Mikami Y., Taguri M., Sakakibara R., Aoki Y., Nanki K., Kawaguchi T., Yoshimatsu Y., Sugimoto S., Sujino T., Takabayashi K., Hosoe N., Ogata H., Kato M., Iwao Y., Nakamoto N., Kanai T.

    Annals of Medicine 57 （ 1 ） 2453083 2025年

    ISSN  07853890

    　概要を見る

    Background and objective: Leucine-rich alpha-2 glycoprotein (LRG) is a novel biomarker for Crohn’s disease (CD). The utility of combination use of LRG and C-reactive protein (CRP) has not been reported. This study aimed to investigate the diagnostic performance of LRG in combination with CRP to predict endoscopic activity. Methods: A single-centre, retrospective, cross-sectional study was conducted. Patients with CD who had serum LRG concentrations measured at least once between June 2020 and May 2021 were enrolled. Clinical activity was evaluated with the Harvey–Bradshaw Index (HBI). Spearman’s rank correlation coefficient (rs) was used to analyse the correlations between the HBI, LRG concentrations and CRP concentrations. In patients undergoing ileocolonoscopy or balloon-assisted enteroscopy within 60 days before or after LRG measurement, endoscopic activity was evaluated with the simple endoscopic score for Crohn’s disease (SES-CD). The diagnostic performance of LRG and CRP for endoscopic activity was evaluated using receiver operating characteristic (ROC) analysis. Results: Four hundred and eighty-nine measurements in 343 patients were analysed. Although a strong correlation was found between LRG and CRP concentrations (rs = 0.75), the HBI did not well correlate with LRG or CRP concentrations. Endoscopic activity was analysed in 56 patients. In diagnosing endoscopically moderate to severe activity (SES-CD > 6), the area under the ROC curve of LRG was greater than that of CRP (0.74 vs. 0.63; p = .037). The optimal cut-off value estimated by Youden’s index was 15.5 µg/mL for LRG, and 0.13 mg/dL for CRP. LRG and CRP concentrations were considered positive when they were above these cut-off values, and the sensitivity and specificity for an SES-CD > 6 were 58.3% and 93.8%, respectively. Dual positivity of LRG and CRP showed the highest specificity. Conclusions: Combination use of dual positive LRG and CRP is useful for diagnosing endoscopically moderate to severe disease.

  • Adjustment of Surveillance Intervals for Ulcerative Colitis-Associated Neoplasia Based on Disease Duration

    Sakakibara R., Sugimoto S., Kaieda Y., Kiyohara H., Yoshimatsu Y., Takabayashi K., Murakami S., Kawaida M., Sujino T., Hosoe N., Kato M., Iwao Y., Mikami Y., Kanai T.

    Digestive Endoscopy 2025年

    ISSN  09155635

    　概要を見る

    Objectives: The risk of colitis-associated cancer increases with disease duration in ulcerative colitis (UC), yet surveillance colonoscopy protocols generally stratify risk uniformly for patients with disease lasting over 8 years. This study evaluated whether shorter surveillance intervals might enhance lesion detection rates in patients with extended disease duration. Methods: This retrospective observational study analyzed patients diagnosed with UC-associated neoplasms between 2010 and 2023. Colonoscopies before lesion detection were retrospectively reviewed, and risk stratification was applied according to four established guidelines. The recommended surveillance intervals were recalculated based on the stratified risk, and lesion detection rates were compared across increasing risk categories for specific disease duration. Results: A total of 39 patients were included, with a median disease duration of 21 years (14–27), and a median colonoscopy interval of 1.3 years (1.1–2.2). Lesion detection rates were 72%, 59%, 44%, and 56% for American Society for Gastrointestinal Endoscopy (ASGE), American Gastroenterological Association (AGA), European Crohn's and Colitis Organisation (ECCO), and British Society of Gastroenterology (BSG) guidelines, respectively. Adjusting risk stratification upward by one rank for disease durations of ≥ 15, ≥ 20, ≥ 25, and ≥ 30 years resulted in increased detection rates: 90%, 87%, 82%, and 72% for ASGE; 85%, 82%, 74%, and 64% for AGA; 82%, 74%, 62%, and 49% for ECCO; and 82%, 79%, 72%, and 62% for BSG, respectively. The longest period with a significant difference in detection rates was observed in patients with disease durations of 20–25 years. Conclusions: For patients with long-standing UC, reducing surveillance intervals may improve the detection of colitis-associated neoplasia, with a practical focus on those with 20–25 years of disease duration.

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競争的研究費の研究課題 【 表示 ／ 非表示 】

  • 疾患組織再構築による生体内での腸管病変の可視化

    2024年06月
    -
    2026年03月

    杉本 真也, 挑戦的研究（萌芽）, 補助金,  研究代表者

  • 細胞移植による腸管上皮機能の変換

    2023年04月
    -
    2026年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 杉本 真也, 基盤研究(B), 補助金,  研究代表者

  • 短腸症候群モデルを用いた新規移植療法の開発

    2021年07月
    -
    2023年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 杉本 真也, 挑戦的研究（萌芽）, 補助金,  研究代表者

  • 小腸上皮オルガノイドにより創出した移植グラフトの機能解析

    2020年04月
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    2023年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 杉本 真也, 基盤研究(B), 補助金,  研究代表者

  • 腸管AhRワールドの解明

    2019年02月
    -
    2021年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 金井 隆典, 国際共同研究加速基金(国際共同研究強化(B)), 研究分担者

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受賞 【 表示 ／ 非表示 】

  • 第60回日本消化器免疫学会総会奨励賞

    2023年10月

    受賞区分： 国内学会・会議・シンポジウム等の賞

  • 第31回日本医学会総会奨励賞　内科領域

    2023年04月

    受賞区分： 国内学会・会議・シンポジウム等の賞

  • 若手奨励賞

    2022年10月, 第30回日本消化器関連学会週間（JDDW 2022 FUKUOKA）

    受賞区分： 国内学会・会議・シンポジウム等の賞

  • 第5回同窓会賞（基礎研究分野 猿田享男賞）

    2022年07月, 慶應義塾大学医学部内科学教室

    受賞区分： 塾内表彰等

  • The 11th JSGE-UEG Rising Stars

    2022年04月, The Japanese Society of Gastroenterology - United European Gastroenterology

    受賞区分： 国際学会・会議・シンポジウム等の賞

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担当授業科目 【 表示 ／ 非表示 】

  • 内科学（消化器）講義

    2025年度

  • 内科学（消化器）講義

    2024年度

  • 内科学（消化器）講義

    2023年度

  • 内科学（消化器）講義

    2022年度

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