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METHOD FOR PRODUCING PLURIPOTENT STEM CELL-DERIVED INTESTINAL ORGANOID NEW

外国特許コード F200010201
整理番号 (S2019-0035-N0)
掲載日 2020年7月30日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2019JP042938
国際公開番号 WO 2020091020
国際出願日 令和元年10月31日(2019.10.31)
国際公開日 令和2年5月7日(2020.5.7)
優先権データ
  • 特願2018-207108 (2018.11.2) JP
  • 特願2019-092336 (2019.5.15) JP
発明の名称 (英語) METHOD FOR PRODUCING PLURIPOTENT STEM CELL-DERIVED INTESTINAL ORGANOID NEW
発明の概要(英語) The present invention addresses the problem of producing an intestinal organoid, having characteristics more similar to a small intestine of a living body, from pluripotent stem cells. The intestinal organoid is produced from pluripotent stem cells by: (1) a step of differentiating the pluripotent stem cells into endoderm-like cells; (2) a step of differentiating the endoderm-like cells obtained in the step (1) into intestinal stem cell-like cells; (3) a step of culturing the intestinal stem cell-like cells obtained in the step (2) in the presence of an epidermal growth factor, a fibroblast growth factor, a TGFβ receptor inhibitor, a GSK-3β inhibitor and a ROCK inhibitor; (4) a step of forming a spheroid by culturing the cells after the step (3); (5) a step of forming the intestinal organoid by differentiating the spheroid formed in the step (4), wherein the intestinal organoid is produced by a step including a cultivation in the presence of an epidermal growth factor, a BMP inhibitor and a Wnt signal activator. Additionally, the cells constituting the intestinal organoid formed in the step (5) are subjected to planar culture in the presence of an epidermal growth factor and a TGFβ receptor inhibitor to produce a planar culture system. Gas-liquid culture is used during the planar culture to build a high-function evaluation system having a villi structure.
従来技術、競合技術の概要(英語) BACKGROUND ART
Small intestine may be orally administered medicament very important to consider the dynamic body is an organ. In non-clinical trials of drugs in human small intestine (absorption, excretion, metabolism) the kinetics of the small intestine for comprehensively evaluating the primary use of epithelial cells is desirable, this is difficult to obtain. In recent years, as new in vitro evaluation system, and intestinal tissue 3 to mimic the three-dimensional tissue structures are of interest (organoids). Organoid is the intestinal tract, bowel disease is important for the research and treatment expected to increase as the tool. Experimentally derived from human tissue present in the gastrointestinal tract organoids are used, very high-intrusive, and very difficult to obtain stable supply. Therefore, low-intrusive, can be used as a disease model for human induced pluripotent stem (iPS) cells such as intestinal organoids is derived from the target.
Also, a non-human mammal and disease model is useful in biomedical research. In particular, in experimental animals used in drug discovery as human and monkey are very similar in many points, the drug-metabolizing enzyme or transporter homology of the amino acid sequence of 90-95% is observed, similar substrate specificities. Therefore in the non-clinical trials, as well as in vitro in vivo using Cynomolgous is possible to confirm the correlation, to more accurately predict a human can.
ES cells or iPS cells 2 from the three-dimensional (2D) culture produced by the intestinal epithelium cells (for example Patent Document 1, reference 2), and the like using two-dimensional 3 Matrigel (3D) culture produced by organoids in the gastrointestinal tract (for example, Patent Document 3, 4, Non-Patent Document 1-4) are reported.
  • 出願人(英語)
  • ※2012年7月以前掲載分については米国以外のすべての指定国
  • NAGOYA CITY UNIVERSITY
  • 発明者(英語)
  • MATSUNAGA Tamihide
  • IWAO Takahiro
  • ONOZATO Daichi
  • OGAWA Isamu
国際特許分類(IPC)
指定国 National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN BR BW BY BZ CA CH CL CN CO CR CU CZ DE DJ DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JO JP KE KG KH KN KP KR KW KZ LA LC LK LR LS LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PA PE PG PH PL PT QA RO RS RU RW SA SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW KM ML MR NE SN ST TD TG
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