Reconstruction of Intestinal Epithelial Stem Cell Niche and Therapeutic Application

• Project/Area Number: 15K08972
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Sapporo Medical University
• Principal Investigator: Arimura Yoshiaki 札幌医科大学, 医学部, 研究員 (80305218)
• Co-Investigator(Kenkyū-buntansha): 永石 歓和 札幌医科大学, 医学部, 講師 (30544118) ; 山下 健太郎 札幌医科大学, 医学部, 講師 (90381269) ; 仲瀬 裕志 札幌医科大学, 医学部, 教授 (60362498)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 骨髄間葉系幹細胞 / 炎症性腸疾患 / 幹細胞ニッチ

Outline of Final Research Achievements

Inflammatory bowel disease (IBD) is a chronic refractory disease repeating relapse and remission. Currently, drug therapy with an effect of suppressing inflammation is mainly used for patients with IBD, but despite adequate control of inflammation, there is a group of patients in which epithelial regeneration is impaired. Therefore, the development of curative therapy leading to intestinal epithelial regeneration is an extremely important research subject. In order to artificially reconstruct a more physiological intestinal epithelial stem cell (ISC) niche ex vivo using bone marrow mesenchymal stem cells, this research aims to establish the isolation and culture technology of rat ISC, We worked on the creation of organoid by co-culture of Enteroid and MSC and established the method.

Research Products

• [Journal Article] Establishment of a refined culture method for rat colon organoids. (2017)
  • Author(s): Isshiki H, Arimura Y, Nagaishi K, Kawakami K, Onodera K, Yamashita K, Naishiro Y, Fujimiya M, Imai K, Shinomura Y.
  • Journal Title: Biochem Biophys Res Commun. Volume: 489 Issue: 3 Pages: 305-311
  • DOI: 10.1016/j.bbrc.2017.05.142
  • Peer Reviewed / Open Access
• [Journal Article] Osteopontin attenuates acute gastrointestinal graft-versus-host disease by preventing apoptosis of intestinal epithelial cells. (2017)
  • Author(s): Kawakami K, Minami N, Matsuura M, Iida T, Toyonaga T, Nagaishi K, Arimura Y, Fujimiya M, Uede T, Nakase H.
  • Journal Title: Biochem Biophys Res Commun. Volume: 485 Issue: 2 Pages: 468-475
  • DOI: 10.1016/j.bbrc.2017.02.047
  • Peer Reviewed / Open Access
• [Journal Article] Is Osteopontin a Friend or Foe of Cell Apoptosis in Inflammatory Gastrointestinal and Liver Diseases? (2017)
  • Author(s): Iida T, Wagatsuma K, Hirayama D, Nakase H.
  • Journal Title: Int J Mol Sci. Volume: 19 Issue: 1 Pages: 7-7
  • DOI: 10.3390/ijms19010007
  • Peer Reviewed / Open Access
• [Journal Article] The Phagocytic Function of Macrophage-Enforcing Innate Immunity and Tissue Homeostasis. (2017)
  • Author(s): Hirayama D, Iida T, Nakase H.
  • Journal Title: Int J Mol Sci. Volume: 19 Issue: 1 Pages: 92-92
  • DOI: 10.3390/ijms19010092
  • Peer Reviewed / Open Access
• [Journal Article] 骨髄―腸管連関の解明と治療応用 (2017)
  • Author(s): 永石歓和，山下健太郎，有村佳昭，仲瀬裕志
  • Journal Title: Medical Science Digest Volume: 43 Pages: 72-75
  • Acknowledgement Compliant
• [Journal Article] Malignant potential of gastrointestinal cancers assessed by structural equation modeling (2016)
  • Author(s): Shimizu H, Arimura Y, Onodera K, Takahashi H, Okahara S, Kodaira J, Oohashi H, Isshiki H, Kawakami K, Yamashita K, Shinomura Y, Hosokawa M
  • Journal Title: PLoS ONE Volume: 11 Issue: 2 Pages: e0149327-e0149327
  • DOI: 10.1371/journal.pone.0149327
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 間葉系幹細胞を用いた消化管再生医療 (2016)
  • Author(s): 川上賢太郎，永石歓和，有村佳昭
  • Journal Title: Medical Science Digest Volume: 42 Pages: 65-68
  • Acknowledgement Compliant
• [Journal Article] Low-frequency IL23R coding variant associated with Crohn's disease susceptibility in Japanese subjects identified by personal genomics analysis (2015)
  • Author(s): Onodera K, Arimura Y, Isshiki H, Kawakami K, Nagaishi K, Yamashita K, Yamamoto E, Niinuma T, Naishiro Y, Suzuki H, Imai K, Shinomura Y
  • Journal Title: PLoS ONE Volume: 10 Issue: 9 Pages: e0137801-e0137801
  • DOI: 10.1371/journal.pone.0137801
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] ラット大腸3次元培養における間葉系幹細胞のニッチ作用 (2016)
  • Author(s): 川上賢太郎, 一色裕之, 有村佳昭, 小野寺馨, 永石歓和, 山下健太郎, 藤宮峯子, 仲瀬裕志
  • Organizer: JDDW 2016
  • Place of Presentation: 神戸国際展示場（兵庫県，神戸市）
• [Presentation] パーソナルゲノム解析を通じた日本人クローン病感受性遺伝子の探索 (2016)
  • Author(s): 小野寺馨, 有村佳昭, 榮浪洋介, 横山佳浩, 山本至, 一色裕之, 川上賢太郎, 久保俊之, 山下健太郎, 仲瀬裕志
  • Organizer: JDDW 2016
  • Place of Presentation: 神戸国際展示場（兵庫県，神戸市）