Development of a novel drug-delivery system by a bio-capsule that is built by primary intestinal epithelial cells.

2012 Fiscal Year Final Research Report

• Project/Area Number: 23659394
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: WATANABE Mamoru 東京医科歯科大学, 医歯学総合研究科, 教授 (10175127)
• Co-Investigator(Renkei-kenkyūsha): NAKAMURA Tetsuya 東京医科歯科大学, 医歯学総合研究科, 准教授 (70265809)
• Project Period (FY): 2011 – 2012
• Keywords: 腸管上皮 / バイオカプセル / 薬剤デリバリー / 炎症性腸疾患 / 初代培養法

Research Abstract

Through our studies aimed to establish novel methods to generate “bio-capsules” that are built by intestinal epithelial cells, we succeeded to identify a distinct culture condition, which allows us to produce “bio-capsules” in a highly efficient manner. In addition, we found that the capsules that were generated by the present method are consisted with high number of intestinal stem cells. Also, we confirmed that Rhodamine123, a substrate of P-glycoprotein, could easily accumulate within the inner space of the bio-capsule. These findings establish the basis for the efficient generation of drug-containing, intestinal epithelial cell-derived bio-capsules.

Research Products

• [Journal Article] Bone marrow-mesenchymal stem cells are a major source of interleukin-7 and sustain colitis by forming the niche for colitogenic CD4+ memory T cells (2012)
  • Author(s): Nemoto Y, Kanai T, Takahara M, Oshima S, Nakamura T, Okamoto R, Tsuchiya K, Watanabe M
  • Journal Title: Gut
  • DOI: doi:10.1136/gutjnl-2012-302029
  • Peer Reviewed
• [Journal Article] Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5+ stem cell (2012)
  • Author(s): Yui S, Nakamura T, Sato T, Nemoto Y,Mizutani T, Zheng X, Ichinose S, Nagaishi T, Okamoto R, Tsuchiya K, Clevers H, Watanabe M
  • Journal Title: Nat Med Volume: 18 Pages: 618-623
  • DOI: doi:10.1038/nm.2695
  • Peer Reviewed
• [Journal Article] The development of colitogenic CD4+ T cells is regulated by IL-7 in collaboration with NK cell function in a murine model of colitis (2012)
  • Author(s): Yamaji O, Nagaishi T, Totsuka T, Onizawa M, Suzuki M, Tsuge N, Hasegawa A, Okamoto R, Tsuchiya K, Nakamura T,Arase H, Kanai T, Watanabe M
  • Journal Title: J Immunol Volume: 188(6) Pages: 2524-2536
  • DOI: doi:10.4049/jimmunol.1100371
  • Peer Reviewed
• [Journal Article] Luminal CD4+ T cells penetrate gut epithelial monolayers and egress from lamina propria to blood circulation (2011)
  • Author(s): Nemoto Y, Kanai T, Shinohara T, Ito T, Nakamura T, Okamoto R, Tsuchiya K, Lipp M, Eishi Y, Watanabe M
  • Journal Title: Gastroenterology Volume: 141 Pages: 2130-2139
  • DOI: doi:10.1053/j.gastro.2011.08.035
  • Peer Reviewed
• [Journal Article] Upregulated IL-7R α expression on colitogenic memory CD4+ T cells may participate in the development and persistence of chronic colitis (2011)
  • Author(s): Shinohara T, Nemoto Y, Kanai T, Kameyama K, Okamoto R, Tsuchiya K, Nakamura T, Totsuka T, Ikuta K, Watanabe M
  • Journal Title: J Immunol Volume: 186 Pages: 2623-2632
  • DOI: doi:10.4049/jimmunol.1000057.9
  • Peer Reviewed
• [Presentation] Adult Stem Cell Therapy for Gastrointestinal Diseases (2012)
  • Author(s): Watanabe M
  • Organizer: International Ulcer Week 2012
  • Place of Presentation: Tokyo
  • Year and Date: 2012-07-12
• [Presentation] Regeneration of damaged colon epithelium by transplanted colon Lgr5+ stem cells maintained and expanded in vitro (2012)
  • Author(s): Yui S, Nakamura T, Nemoto Y, Mizutani T, Fukuda M, Nozaki K, Yamauchi Y, Mochiduki W, Zheng X, Nagaishi T, Okamoto R, Tsuchiya K, Watanabe M
  • Organizer: 第10回幹細胞シンポジウム
  • Place of Presentation: 淡路島
  • Year and Date: 2012-06-01
• [Presentation] Stem Cells (2012)
  • Author(s): Watanabe M
  • Organizer: DDW
  • Place of Presentation: San Diego, U.S.A
  • Year and Date: 2012-05-22
• [Presentation] Real-time analysis of p-glycoprotein-mediated drug transport across primary intestinal epitherial cells three-dimensionallycultured in vitro (2012)
  • Author(s): Mizutani T, Nakamura T, Morikawa R, Fukuda M, Mochizuki W, Yamauchi Y,Nozaki K, Yui S, Okamoto R, Tsuchiya K, Watanabe M
  • Organizer: DDW2012
  • Place of Presentation: San Diego, U.S.A
  • Year and Date: 2012-05-21
• [Presentation] Luminal CD4+T cells penetrate gut epithelial monolayers and egress from lamina propia to blood circulation (2011)
  • Author(s): Nemoto Y, Watanabe M
  • Organizer: 第15回国際粘膜免疫学会
  • Place of Presentation: Paris, France
  • Year and Date: 2011-10-25
• [Patent(Industrial Property Rights)] 大腸上皮幹細胞の単離・培養技術と、これを用いた大腸上皮移植技術 (2013)
  • Inventor(s): 渡辺守、中村哲也
  • Industrial Property Rights Holder: 渡辺守、中村哲也
  • Industrial Property Number: 特許 WO2013/061608 A1
  • Acquisition Date: 2013-05-02
  • Overseas