Functional analysis of small intestinal epithelial organoid-based transplant graft
Project/Area Number |
20H03746
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
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Research Institution | Keio University |
Principal Investigator |
SUGIMOTO Shinya 慶應義塾大学, 医学部(信濃町), 助教 (20626387)
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Co-Investigator(Kenkyū-buntansha) |
袴田 陽二 日本獣医生命科学大学, 獣医学部, 教授 (00218380)
小林 英司 慶應義塾大学, 医学部(信濃町), 特任教授 (00245044)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2022: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
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Keywords | 短腸症候群 / 小腸移植 / 幹細胞 / 細胞移植 / 組織修復 / 上皮置換 / 潰瘍性大腸炎 / 炎症性腸疾患 / オルガノイド / 体性幹細胞 / 小腸疾患 / 再生機構 / 臓器再生 / 潰瘍性大腸炎関連腫瘍 / 細胞競合 / 吸収機能 |
Outline of Research at the Start |
腸管上皮幹細胞をオルガノイドとして永続的に体外培養可能となり,研究ツールとしてのみならず,再生医療への応用も期待されている.とりわけ,十分な治療法がなく命を落とす患者の多い難治性小腸疾患に対する革新的な治療法の開発が望まれている.本研究では,ラットおよびヒト小腸上皮オルガノイドを用いて,大腸上皮を小腸上皮オルガノイドで置換することで小腸上皮化大腸を創出し,その機能解析を行うことを目的とする.
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Outline of Final Research Achievements |
Combining the organoid transplantation technique with surgery, we developed a technique to create small intestinalized colon grafts by removing a portion of colonic epithelium from rats and transplanting organoids derived from the small intestine. Functional analysis of intestinal organoids, human small intestinal epithelium transplanted into mouse colon, and small intestinalized colon grafts in rats was performed. We successfully demonstrated the small intestinal function of the epithelium constructed by small intestinal epithelial organoids and confirmed the concept of organoid-based therapy for a small animal model of short bowel syndrome.
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Academic Significance and Societal Importance of the Research Achievements |
小腸上皮は移植した先の組織の構造を変化させ、小腸としての機能を発揮しうることが明らかになった。大腸の上皮を小腸オルガノイドにより置換した小腸化大腸を移植するという新しい治療戦略は、今回コンセプトが確認された小動物(マウス、ラット)と比較してサイズが大きなヒトにおいても応用可能と考えられる。今後、自己の小腸オルガノイドと大腸組織を用いた自家移植を行うことで、免疫抑制剤を必要としない新規治療法の開発へとつながることが期待される。
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Report
(4 results)
Research Products
(72 results)
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[Journal Article] Identification of Quiescent LGR5+ Stem Cells in the Human Colon2022
Author(s)
Ishikawa K, Sugimoto S, Oda M, Fujii M, Toshimitsu K, Sawada K, Shimokawa M, Saito M, Kawasaki K, Ishii R, Taniguchi K, Sato T.
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Journal Title
Gastroenterology.
Volume: 163
Issue: 5
Pages: 1391-1406
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] 潰瘍性大腸炎に伴うdysplasiaに対する内視鏡治療はどのように考えるのか?2022
Author(s)
高林 馨, 杉本 真也, 吉松 裕介, 清原 裕貴, 三上 洋平, 筋野 智久, 河口 貴昭, 加藤 元彦, 細江 直樹, 岩男 泰, 矢作 直久, 金井 隆典, 緒方 晴彦
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Journal Title
消化器・肝臓内科
Volume: 12
Pages: 158-164
Related Report
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[Journal Article] An organoid-based organ-repurposing approach to treat short bowel syndrome2021
Author(s)
Sugimoto S, Kobayashi E, Fujii M, Ohta Y, Arai K, Matano M, Ishikawa K, Miyamoto K, Toshimitsu K, Takahashi S, Nanki K, Hakamata Y, Kanai T, Sato T.
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Journal Title
Nature
Volume: 592
Pages: 99-104
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Mucosal concentrations of N-acetyl-5-aminosalicylic acid is related to endoscopic activity in ulcerative colitis patients with mesalamine.2020
Author(s)
Fukuda T, Naganuma M, Takabayashi K, Hagihara Y, Tanemoto S, Nomura E, Yoshimatsu Y, Sugimoto S, Nanki K, Mizuno S, Mikami Y, Fukuhara K, Sujino T, Mutaguchi M, Inoue N, Ogata H, Iwao Y, Abe T, Kanai T.
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Journal Title
J Gastroenterol Hepatol.
Volume: 35
Issue: 11
Pages: 1878-1885
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Dose escalation of oral 5-aminosalicylic acid for ulcerative colitis with Mayo endoscopic subscore of one improves long-term prognosis: a one-year multicentre, open-label, randomized controlled trial2023
Author(s)
Yasuhiro Aoki, Tomohiro Fukuda, Hiroki Kiyohara, Ayumi Yokoyama, Atsushi Nakazawa, Yusuke Yoshimatsu, Shinya Sugimoto, Kosaku Nanki, Yohei Mikami, Kayoko Fukuhara, Shinta Mizuno, et al.
Organizer
18th Congress of European Crohn’s and Colitis Organization (ECCO 2023)
Related Report
Int'l Joint Research
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[Presentation] Investigation of endoscopic chronological evolution of ulcerative colitis-associated neoplasia2022
Author(s)
Yusuke Wakisaka, Shinya Sugimoto, Yasushi Iwao, Kaoru Takabayashi, Yusuke Yoshimatsu, Hiroki Kiyohara, Takaaki Kawaguchi, Tomohisa Sujino, Naoki Hosoe, Haruhiko Ogata, Yohei Mikami, Takanori Kanai
Organizer
The 10th Annual Meeting of the Asian Organization for Crohn's & Colitis
Related Report
Int'l Joint Research
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[Presentation] Evaluation of diagnostic criteria for Sporadic neoplasm in ulcerative colitis2022
Author(s)
Kaoru Takabayashi, Yasuhiro Aoki, Yusuke Yoshimatsu, Hiroki Kiyohara, Shinya Sugimoto, Yohei Mikami, Tomohisa Sujino, Takaaki Kawaguchi, Naoki Hosoe, Yasushi Iwao, Haruhiko Ogata, Takanori Kanai.
Organizer
The 10th Annual Meeting of the Asian Organization for Crohn's & Colitis
Related Report
Int'l Joint Research
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[Presentation] Successful Combination Therapy with Infliximab and Cyclosporine A for Refractory Myelodysplastic Syndrome associated Small Intestinal Ulcers: A case report2022
Author(s)
Shogo Sunaga, Hiroki Kiyohara, Kurato Miyazaki, Ryosuke Kasuga, Kaoru Takabayashi, Naoki Hosoe, Takaaki Kawaguchi, Yohei Mikami, Kosaku Nanki, Yusuke Yoshimatsu, Shinya Sugimoto, Tomohisa Sujino, Yasushi Iwao, Haruhiko Ogata, Takanori Kanai
Organizer
The 10th Annual Meeting of the Asian Organization for Crohn's & Colitis
Related Report
Int'l Joint Research
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[Presentation] Effectiveness and Durability of Ustekinumab Therapy With or Without Immunomodulators for Ulcerative Colitis Patients2022
Author(s)
Yasuhiro Aoki, Tomohisa Sujino, Takaaki Kawaguchi, Shinya Sugimoto, Fumie Shimada, Yusuke Yoshimatsu, Hiroki Kiyohara, Kosaku Nanki, Yohei Mikami, Kaoru Takabayashi, Naoki Hosoe, Haruhiko Ogata, Yasushi Iwao, Takanori Kanai
Organizer
The 10th Annual Meeting of the Asian Organization for Crohn's & Colitis
Related Report
Int'l Joint Research
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[Presentation] Serum LRG as a novel biomarker of disease and endoscopic activity in patients with Crohn’s disease2022
Author(s)
Yoshiaki Takada, Hiroki Kiyohara, Yohei Mikami, Fumie Shimada, Yuta Matsubara, Ryoya Sakakibara, Yasuhiro Aoki, Masataka Ichikawa, Yusuke Wakisaka, Yuya Hagihara, Shun Tanemoto, Satoko Umeda, Yusuke Yoshimatsu, Keiko Ono, Emi Irie, Shinya Sugimoto, Kosaku Nanki, et al.
Organizer
The 10th Annual Meeting of the Asian Organization for Crohn's & Colitis
Related Report
Int'l Joint Research
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[Presentation] Prognosis in the treatment of the 2nd line anti-TNF inhibitor in patients with ulcerative colitis2022
Author(s)
Hiroki Kiyohara, Takaaki Kawaguchi, Yohei Mikami, Yusuke Yoshimatsu, Shinya Sugimoto, Tomohisa Sujino, Kaoru Takabayashi, Naoki Hosoe, Yasushi Iwao, Haruhiko Ogata, Takanori Kanai
Organizer
The 10th Annual Meeting of the Asian Organization for Crohn's & Colitis
Related Report
Int'l Joint Research
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[Presentation] 内視鏡Mayoスコア1の臨床的寛解潰瘍性大腸炎患者に対する経口5-ASA製剤の増量は臨床的再燃を抑制する2022
Author(s)
福田知広, 青木康浩, 清原裕貴, 横山 歩, 吉松裕介, 杉本真也, 南木康作, 三上洋平, 福原佳代子, 水野慎大, 筋野智久, 牟田口 真, 高林 馨, 諸星雄一, 中澤 敦, 細田泰雄, 緒方晴彦, 岩男 泰, 長沼 誠, 金井隆典
Organizer
第13回日本炎症性腸疾患学会学術集会
Related Report
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[Presentation] 自然整復した成人の特発性小腸重積症の一例2022
Author(s)
韓可, 吉松裕介, 杉本真也, 清原裕貴, 三上洋平, 筋野智久, 河口貴昭, 高林馨, 細江直樹, 緒方晴彦, 金井隆典
Organizer
日本消化器病学会 関東支部第372回例会
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[Presentation] 原因不明の消化管狭窄を来たし、審査腹腔鏡で診断し得た二例2022
Author(s)
水島 一郎, 三上 洋平, 河口 貴昭, 岡田 はるか, 須永 将梧, 津軽 開, 戸ヶ崎 和博, 杉本 真也, 清原 裕貴, 南木 康作, 平田 賢郎, 浜本 康夫, 筋野 智久, 高林 馨, 細江 直樹, 緒方 晴彦, 金井 隆典
Organizer
第368回日本消化器病学会関東支部例会
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[Presentation] 微小変化型ネフローゼ症候群に合併した重症IBD-unclassifiedの一例2021
Author(s)
海江田 祐太, 清原 裕貴, 宮崎 蔵人, 三上 洋平, 河口 貴昭, 南木 康作, 筋野 智久, 高林 馨, 杉本 真也, 細江 直樹, 緒方 晴彦, 岩男 泰, 金井 隆典
Organizer
日本消化器病学会関東支部第366回例会
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[Presentation] IBDにおける適切なモニタリング法の選択 クローン病の疾患活動性モニタリング法としての、血清LRG値の有用性の検討2021
Author(s)
高田 祐明, 三上 洋平, 青木 康浩, 市川 将隆, 脇坂 悠介, 萩原 裕也, 種本 俊, 梅田 智子, 吉松 裕介, 杉本 真也, 清原 裕貴, 南木 康作, 筋野 智久, 河口 貴昭, 高林 馨, 細江 直樹, 緒方 晴彦, 金井 隆典
Organizer
第39回大腸検査学会総会
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[Presentation] Incidence and risk factors of venous thromboembolism in inpatients with inflammatory bowel disease2021
Author(s)
Yasuhiro Aoki, Hiroki Kiyohara, Kosaku Nanki, Yohei Mikami, Takaaki Kawaguchi, Tomohisa Sujino, Shinya Sugimoto, Kaoru Takabayashi, Kayoko Fukuhara, Naoki Hosoe, Haruhiko Ogata, Yasushi Iwao, Takanori Kanai
Organizer
The 9th Annual Meeting of the Asian Organization for Crohn's and Colitis (AOCC 2021)
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Int'l Joint Research
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[Presentation] Continuous intravenous cyclosporine therapy improves short term prognosis in patients with severe ulcerative colitis refractory to multiple molecular target therapies2021
Author(s)
Yuta Matsubara, Hiroki Kiyohara, Yasuhiro Aoki, Tomohiro Fukuda, Kosaku Nanki, Yohei Mikami, Takaaki Kawaguchi, Tomohisa Sujino, Shinya Sugimoto, Kaoru Takabayashi, Kayoko Fukuhara, Naoki Hosoe, Haruhiko Ogata, Yasushi Iwao, Makoto Naganuma, Takanori Kanai
Organizer
The 9th Annual Meeting of the Asian Organization for Crohn's and Colitis (AOCC 2021)
Related Report
Int'l Joint Research
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[Presentation] IBD発癌の諸問題・基礎~臨床まで 血管増生を背景とした境界のある発赤は潰瘍性大腸炎関連平坦型dysplasia発見の有用なマーカーである2021
Author(s)
池端 昭慶, 下田 将之, 岡林 剛史, 茂田 浩平, 清島 亮, 松井 信平, 杉本 真也, 矢作 直久, 金井 隆典, 北川 雄光, 金井 弥栄, 岩男 泰
Organizer
第76回日本大腸肛門病学会学術集会
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[Presentation] 炎症性腸疾患患者における静脈血栓塞栓症の臨床的検討2021
Author(s)
青木 康浩, 清原 裕貴, 南木 康作, 三上 洋平, 河口 貴昭, 筋野 智久, 杉本 真也, 高林 馨, 福原 佳代子, 細江 直樹, 緒方 晴彦, 岩男 泰, 金井 隆典
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第12回日本炎症性腸疾患学会学術集会
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