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 】

  • Gastrointestinal symptoms in COVID-19 and disease severity: a Japanese registry-based retrospective cohort study.

    Matsubara Y, Kiyohara H, Mikami Y, Nanki K, Namkoong H, Chubachi S, Tanaka H, Azekawa S, Sugimoto S, Yoshimatsu Y, Sujino T, Takabayashi K, Hosoe N, Sato T, Ishii M, Hasegawa N, Okada Y, Koike R, Kitagawa Y, Kimura A, Imoto S, Miyano S, Ogawa S, Fukunaga K, Kanai T, Japan COVID-19 Task Force

    Journal of gastroenterology  2024.01

    ISSN  0944-1174

  • Clinical challenges of short bowel syndrome and the path forward for organoid-based regenerative medicine

    Endo R., Sugimoto S., Shirosaki K., Kato H., Wada M., Kanai T., Sato T.

    Regenerative Therapy （Regenerative Therapy)  24   64 - 73 2023.12

    　View Summary

    Short bowel syndrome (SBS) is a rare condition, the main symptom of which is malabsorption following extensive resection of the small intestine. Treatment for SBS is mainly supportive, consisting of supplementation, prevention and treatment of complications, and promotion of intestinal adaptation. While development of parenteral nutrition and drugs promoting intestinal adaptation has improved clinical outcomes, the prognosis of patients with SBS remains poor. Intestinal transplantation is the only curative therapy but its outcome is unsatisfactory. In the absence of definitive therapy, novel treatment is urgently needed. With the advent of intestinal organoids, research on the intestine has developed remarkably in recent years. Concepts such as the “tissue-engineered small intestine” and “small intestinalized colon,” which create a functional small intestine by combining organoids with other technologies, are potentially novel regenerative therapeutic approaches for SBS. Although they are still under development and there are substantial issues to be resolved, the problems that have prevented establishment of the complex function and structure of the small intestine are gradually being overcome. This review discusses the current treatments for SBS, the fundamentals of the intestine and organoids, the current status of these new technologies, and future perspectives.

  • Characteristics of flat-type ulcerative colitis-associated neoplasia on chromoendoscopic imaging with indigo carmine dye spraying.

    Takabayashi K, Sugimoto S, Nanki K, Yoshimatsu Y, Kiyohara H, Mikami Y, Sujino T, Kato M, Hosoe N, Shimoda M, Yahagi N, Ogata H, Iwao Y, Kanai T

    Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society （Digestive Endoscopy)   2023.06

    ISSN  0915-5635

    　View Summary

    Objectives: Despite recent advances in endoscopic equipment and diagnostic techniques, early detection of ulcerative colitis-associated neoplasia (UCAN) remains difficult because of the complex background of the inflamed mucosa of ulcerative colitis and the morphologic diversity of the lesions. We aimed to describe the main diagnostic patterns for UCAN in our cohort, including lateral extension surrounding flat lesions. Methods: Sixty-three lesions in 61 patients with flat-type dysplasia that were imaged with dye chromoendoscopy (DCE) were included in this analysis. These DCE images were analyzed to clarify the dye-chromoendoscopic imaging characteristics of flat dysplasia, and the lesions were broadly classified into dysplastic and nondysplastic mucosal patterns. Results: Dysplastic mucosal patterns were classified into two types: small round patterns with round to roundish structures, and mesh patterns with intricate mesh-like structures. Lesions with a nondysplastic mucosal pattern were divided into two major types: a ripple-like type and a gyrus-like type. Of note, 35 lesions (55.6%) had a small round pattern, and 51 lesions (80.9%) had some type of mesh pattern. About 70% of lesions with small round patterns and 49% of lesions with mesh patterns were diagnosed as high-grade dysplasia or carcinoma, while about 30% of lesions with small round patterns and 51% of lesions with mesh patterns were diagnosed as low-grade dysplasia. Conclusion: When a characteristic mucosal pattern, such as a small round or mesh pattern, is found by DCE, the possibility of UCAN should be considered.

  • Bacteriophage therapy against pathological Klebsiella pneumoniae ameliorates the course of primary sclerosing cholangitis.

    Ichikawa M, Nakamoto N, Kredo-Russo S, Weinstock E, Weiner IN, Khabra E, Ben-Ishai N, Inbar D, Kowalsman N, Mordoch R, Nicenboim J, Golembo M, Zak N, Jablonska J, Sberro-Livnat H, Navok S, Buchshtab N, Suzuki T, Miyamoto K, Teratani T, Fujimori S, Aoto Y, Konda M, Hayashi N, Chu PS, Taniki N, Morikawa R, Kasuga R, Tabuchi T, Sugimoto S, Mikami Y, Shiota A, Bassan M, Kanai T

    Nature communications （Nature Communications)  14 （ 1 ） 3261 2023.06

    　View Summary

    Primary sclerosing cholangitis (PSC) is characterized by progressive biliary inflammation and fibrosis. Although gut commensals are associated with PSC, their causative roles and therapeutic strategies remain elusive. Here we detect abundant Klebsiella pneumoniae (Kp) and Enterococcus gallinarum in fecal samples from 45 PSC patients, regardless of intestinal complications. Carriers of both pathogens exhibit high disease activity and poor clinical outcomes. Colonization of PSC-derived Kp in specific pathogen-free (SPF) hepatobiliary injury-prone mice enhances hepatic Th17 cell responses and exacerbates liver injury through bacterial translocation to mesenteric lymph nodes. We developed a lytic phage cocktail that targets PSC-derived Kp with a sustained suppressive effect in vitro. Oral administration of the phage cocktail lowers Kp levels in Kp-colonized germ-free mice and SPF mice, without off-target dysbiosis. Furthermore, we demonstrate that oral and intravenous phage administration successfully suppresses Kp levels and attenuates liver inflammation and disease severity in hepatobiliary injury-prone SPF mice. These results collectively suggest that using a lytic phage cocktail shows promise for targeting Kp in PSC.

  • Risk of venous thromboembolism with a central venous catheter in hospitalized Japanese patients with inflammatory bowel disease: a propensity score-matched cohort study.

    Aoki Y, Kiyohara H, Mikami Y, Nanki K, Kawaguchi T, Yoshimatsu Y, Sugimoto S, Sujino T, Takabayashi K, Hosoe N, Ogata H, Iwao Y, Kanai T

    Intestinal research （Intestinal Research)  21 （ 3 ） 318 - 327 2023.02

    ISSN  1598-9100

    　View Summary

    Background/Aims: Thromboprophylaxis is recommended for hospitalized patients with inflammatory bowel disease (IBD) in Western countries, although it is selectively administered to high-risk patients in East Asia. A central venous catheter (CVC) is commonly placed in patients with IBD. Although CVC placement is considered a risk factor for venous thromboembolism (VTE), the degree of increased risk in patients with IBD is uncertain. This study aimed to identify the risk of VTE with CVC placement in hospitalized Japanese patients with IBD without thromboprophylaxis. Methods: This retrospective cohort study included patients with ulcerative colitis or Crohn’s disease who were admitted for disease flares at Keio University Hospital between January 2016 and December 2020. Patients who already had thrombosis or were administered any antithrombotic treatment on admission were excluded. VTE development during the hospitalization was surveyed, and VTE risk associated with CVC indwelling was estimated using propensity score matching and inverse probability of treatment weighting analyses. Results: Altogether, 497 hospitalized patients with IBD (ulcerative colitis, 327; Crohn’s disease, 170) were enrolled. VTE developed in 9.30% (12/129) of catheterized patients and in 0.82% (3/368) of non-catheterized patients. The propensity score matching yielded 127 matched pairs of patients. The catheterized group demonstrated higher odds for VTE than the non-catheterized group (odds ratio, 13.15; 95% confidence interval, 1.68–102.70). A similar result was obtained in the inverse probability of treatment weighting analysis (odds ratio, 11.02; 95% confidence interval, 2.64–46.10). Conclusions: CVC placement is a major risk factor for VTE among hospitalized Japanese patients with IBD without thromboprophylaxis.

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Reviews, Commentaries, etc. 【 Display / hide 】

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

  • 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)

  • 腸管上皮－間質ニッチの包括的理解と自己補完的組織培養技術の確立

    2015.04
    -
    2018.03

    文部科学省・日本学術振興会, 科学研究費助成事業, 特別研究員奨励費, Principal investigator

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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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