Sugimoto, Shinya

写真a

Affiliation

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

Position

Instructor
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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 】

  • Understanding the Differentiation Pathway to BEST4(+) Cells in Human Colonic Epithelium.

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

    Gastroenterology  2025.02

    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  2025.01

    ISSN  0944-1174

    　View Summary

    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

    ISSN  07853890

    　View Summary

    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.

  • Ulcerative colitis-associated neoplasms often harbor poor prognostic histologic components with low detection by biopsy.

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

    Intestinal research 22 ( 4 ) 428 - 438 2024.05

    ISSN  1598-9100

    　View Summary

    Background/Aims: Poorly differentiated adenocarcinoma, signet-ring cell carcinoma, and mucinous adenocarcinoma (por/sig/muc), which are considered to be histologic subtypes with a poor prognosis, occur more frequently with colitis-associated cancer than with sporadic tumors. However, their invasiveness and manifestations are unclear. This study aimed to determine the prevalence of the por/sig/muc component in ulcerative colitis-associated neoplasms (UCANs) and its association with invasiveness and to clarify its clinicohistologic and endoscopic features. Methods: This retrospective observational study included patients diagnosed with ulcerative colitis-associated high-grade dysplasia or adenocarcinoma from 1997 to 2022 who were divided according to the presence or absence of a por/sig/muc component. Results: Thirty-five patients had UCAN with a por/sig/muc component and 66 had UCAN without this component. The 5-year survival rate was significantly lower in the por/sig/muc group than in the tub group (67% vs. 96%, P=0.001), which was attributed to disease above stage III and depth to below the subserosa. Biopsy-based diagnosis before resection detected a por/sig/muc component in only 40% of lesions (14/35). Lesions with a por/sig/muc component were prevalent even in the early stages: stage 0 (4/36, 11%), I (8/20, 40%), II (7/12, 58%), III (10/14, 71%), and IV (6/8, 75%). Conclusions: This is the first investigation that shows UCANs with a por/sig/muc component tended to be deeply invasive and were often not recognized preoperatively. Endoscopists should be aware that UCAN often has a por/sig/muc component that is not always recognized on biopsy, and the optimal treatment strategy needs to be carefully considered.

  • Efficacy of Dose Escalation of Oral 5-Aminosalicylic Acid for Ulcerative Colitis With a Mayo Endoscopic Subscore of 1: An Open Label Randomized Controlled Trial.

    Fukuda T, Aoki Y, Kiyohara H, Yokoyama A, Nakazawa A, Yoshimatsu Y, Sugimoto S, Nanki K, Mikami Y, Fukuhara K, Mizuno S, Sujino T, Mutaguchi M, Takabayashi K, Morohoshi Y, Hosoda Y, Ogata H, Iwao Y, Naganuma M, Kanai T

    Inflammatory bowel diseases 31 ( 3 ) 716 - 724 2024.04

    ISSN  1078-0998

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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)

    2024

  • LECTURE SERIES, INTERNAL MEDICINE (GASTROENTEROLOGY)

    2023

  • LECTURE SERIES, INTERNAL MEDICINE (GASTROENTEROLOGY)

    2022

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