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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論文 【 表示 ／ 非表示 】

  • 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 2023年02月

    ISSN  1598-9100

  • DEVELOPMENT AND APPLICATION OF WATER-AIDED COLONOSCOPY

    Mizukami T., Sugimoto S.

    Gastroenterological Endoscopy （Gastroenterological Endoscopy)  65 （ 1 ） 19 - 28 2023年01月

    ISSN  03871207

    　概要を見る

    The sigmoid colon tends to form loops and bends easily and is therefore considered a difficult site for colonoscope insertion. Inexperienced trainees may accidentally dilate the sigmoid colon following excessive air insufflation, and colonoscope insertion is challenging in such cases even with the use of the axis-retaining shortening method. The water infusion method developed in Japan involves injection of a small amount of water, which facilitates shortening and straightening. The collapse-submergence method, which includes a combination of degassing at the sigmoid colon and the water infusion method, is an improved technique that eliminates the water-air interface to provide a better field of view. The water immersion method can be easily learned even by trainees and is shown to improve the cecal intubation rate and suppress loop formation, which minimizes patient discomfort. This method is also utilized to perform detorsion of sigmoid volvulus and evaluation of irritable bowel syndrome and intestinal morphological abnormalities. Water-aided colonoscopy is popular in the U.S. and Europe, and studies have reported improved adenoma detection rates using “water exchange.” This innovative method is not only useful for endoscope insertion but also aids with underwater endoscopic mucosal resection. Water infusion-related techniques put to advantage the characteristics of water and overcome the limitations encountered with air insufflation methods and are expected to become increasingly popular in the future.

  • In Vivo Intestinal Research Using Organoid Transplantation.

    Sugimoto S, Kobayashi E, Kanai T, Sato T

    The Keio journal of medicine （Keio Journal of Medicine)  71 （ 4 ） 73 - 81 2022年12月

    ISSN  0022-9717

    　概要を見る

    Our understanding of the biology of the intestinal epithelium has advanced since the establishment of an organoid culture system. Although organoids have enabled investigation of the mechanism of self-renewal of human intestinal stem cells in vitro, it remains difficult to clarify the behavior of human normal and diseased intestinal epithelium in vivo. Recently, we developed a xenotransplantation system in which human intestinal organoids are engrafted onto epithelium-depleted mouse colons. This xenograft recapitulated the original tissue structures. Upon xenotransplantation, normal colon organoids developed normal colon crypt structures without tumorigenesis, whereas tumor-derived organoids formed colonic tumors resembling the original tumors. The non-tumorigenicity of human intestinal organoids highlights the safety of organoid-based regenerative medicine. As an example of regenerative medicine for short bowel syndrome, we devised a unique organ-repurposing approach to convert colons into small intestines by organoid transplantation. In this approach, the transplanted rat small intestinal organ-oids not only engrafted onto the rat colons but also remodeled the colon subepithelial structures into a small intestine-like conformation. Luminal flow accelerated the maturation of villi in the small intes-tine, which promoted the formation of a lymphovascular network mimicking lacteals. In this review, we provide an overview of recent advances in gastrointestinal organoid transplantation and share our understanding of human disease biology and regenerative medicine derived from these studies.

  • Usefulness of Texture and Color Enhancement Imaging (TXI) in Assessing Mucosal Healing in Patients with Ulcerative Colitis.

    Hayashi Y, Takabayashi K, Kato M, Tojo A, Aoki Y, Hagihara Y, Yoshida K, Yoshimatsu Y, Kiyohara H, Sugimoto S, Nanki K, Mikami Y, Sujino T, Mutaguchi M, Kawaguchi T, Hosoe N, Yahagi N, Ogata H, Kanai T

    Gastrointestinal endoscopy （Gastrointestinal Endoscopy)  97 （ 4 ） 759 - 766.e1 2022年11月

    ISSN  0016-5107

    　概要を見る

    Background and aims: Endoscopic remission is known to be defined as a Mayo endoscopic subscore (MES) of ≤1 in patients with ulcerative colitis (UC). However, some individuals experience relapse even after showing endoscopic remission under white-light imaging (WLI), and no tool exists that can detect these individuals. The aim of this study was to clarify the usefulness of texture and color enhancement imaging (TXI) in the assessment of inflammation in patients with UC. Methods: This was a prospective, single-arm, observational study conducted at a university hospital. From January 2021 to December 2021, 146 UC patients with endoscopic remission were enrolled. Images were evaluated by WLI, TXI, and pathologic evaluation, followed by prognostic studies. The primary endpoint of the study was the cumulative relapse of UC in each TXI score. The secondary endpoints were the association between TXI and pathologic scores, predictors of relapse, and interobserver agreement between the MES and TXI scores. Results: Patients with TXI score 2 had significantly lower UC relapse-free rates than did those with TXI scores 0-1 (log-rank test, P < .01). When pathologic remission was defined as Matts grade ≤2, the rate of pathologic remission decreased significantly with higher TXI scores (P = .01). In multivariate analysis, TXI score 2 was the only risk factor for UC relapse (P < .01; hazard ratio, 4.16; 95% confidence interval, 1.72-10.04). Interobserver agreement on the TXI score was good (κ = 0.597-0.823). Conclusion: TXI can be used to identify populations with poor prognosis in MES 1, for whom treatment intensification has been controversial.

  • CXCL16 inhibits epithelial regeneration and promotes fibrosis during the progression of radiation enteritis.

    Cui Y, Wu H, Liu Z, Ma T, Liang W, Zeng Q, Chen D, Qin Q, Huang B, Wang MH, Huang X, He Y, Kuang Y, Sugimoto S, Sato T, Wang L

    The Journal of pathology （Journal of Pathology)  259 （ 2 ） 180 - 193 2022年11月

    ISSN  0022-3417

    　概要を見る

    Radiation enteritis (RE) is a prevalent complication of radiotherapy for pelvic malignant tumors, characterized by severe intestinal epithelial destruction and progressive submucosal fibrosis. However, little is known about the pathogenesis of this disease, and so far, there is no specific targeted therapy. Here, we report that CXCL16 is upregulated in the injured intestinal tissues of RE patients and in a mouse model. Genetic deletion of Cxcl16 mitigates fibrosis and promotes intestinal stem cell-mediated epithelial regeneration after radiation injury in mice. Mechanistically, CXCL16 functions on myofibroblasts through its receptor CXCR6 and activates JAK3/STAT3 signaling to promote fibrosis and, at the same time, to transcriptionally modulate the levels of BMP4 and hepatocyte growth factor (HGF) in myofibroblasts. Moreover, we find that CXCL16 and CXCR6 auto- and cross-regulate themselves in positive feedback loops. Treatment with CXCL16 neutralizing monoclonal antibody attenuates fibrosis and improves the epithelial repair in RE mouse model. Our findings emphasize the important role of CXCL16 in the progression of RE and suggest that CXCL16 signaling could be a potential therapeutic target for RE. © 2022 The Pathological Society of Great Britain and Ireland.

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総説・解説等 【 表示 ／ 非表示 】

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競争的研究費の研究課題 【 表示 ／ 非表示 】

  • 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
    -
    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

  • 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年04月
    -
    2018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, 特別研究員奨励費, 補助金,  研究代表者

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受賞 【 表示 ／ 非表示 】

  • 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

  • 令和4年度 科学技術分野の文部科学大臣表彰 若手科学者賞

    2022年04月

    受賞区分： その他

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担当授業科目 【 表示 ／ 非表示 】

  • 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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