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INDUCTION OF DIFFERENTIATION OF INDUCED PLURIPOTENT STEM CELLS INTO INTESTINAL EPITHELIAL CELLS

外国特許コード F170009236
整理番号 (S2016-0443-N0)
掲載日 2017年9月21日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2017JP008616
国際公開番号 WO 2017154795
国際出願日 平成29年3月3日(2017.3.3)
国際公開日 平成29年9月14日(2017.9.14)
優先権データ
  • 特願2016-044088 (2016.3.8) JP
発明の名称 (英語) INDUCTION OF DIFFERENTIATION OF INDUCED PLURIPOTENT STEM CELLS INTO INTESTINAL EPITHELIAL CELLS
発明の概要(英語) This invention addresses the problem of providing: a novel method that allows, in a simple manner, preparation of cells that exhibit a function similar to that of intestinal epithelial cells of a living body; and an application therefor. Induced pluripotent stem cells are induced to differentiate into intestinal epithelial cells by: (1) a step for differentiating the induced pluripotent stem cells into endoderm-like cells; (2) a step for differentiating the endoderm-like cells obtained in step (1) into intestinal stem cell-like cells; and (3) a step for differentiating the intestinal stem cell-like cells obtained in step (2) into intestinal epithelial cell-like cells, the step including culturing in the presence of an MEK1 inhibitor, a DNA methylation inhibitor, a TGFβ receptor inhibitor, and EGF, and in a condition in which cAMP is fed to the cells.
従来技術、競合技術の概要(英語) BACKGROUND ART
A number of the small intestine the drug-metabolizing enzyme or drug transporter because of the presence, in the same manner as the liver, as an organ relating to the first-pass effect of the drug which is very important. Therefore, early stages of drug development from the membrane permeability of the medicament in the small intestine to evaluate and metabolism, the development of pharmaceutical products having excellent pharmacokinetic properties required. The present invention is, to cure the photo-curable resin material of the three-dimensional object by a molding technique. However, drug transporter Caco-2 cells different from the expression pattern of human small intestine. In addition, the drug-metabolizing enzyme cells Caco-2 expression and enzyme induction almost not found, accurately to assess the pharmacokinetics of the small intestine is difficult. Therefore, membrane permeability and drug metabolism in the small intestine of an overall evaluation was made for the use of primary small intestine epithelial cells is desirable, it is difficult to obtain primary small intestine epithelial cells.
However, human induced pluripotent stem (induced pluripotent stem: iPS) cells are established by yamanaka et al. in the year 2007. The human iPS cells, established by Thomson et al. in the year 1998 human embryonic stem cells (embryonic stem: ES) similar to, pluripotency and proliferative potential in cells with an almost limitless. Human ES cells may be of human iPS ethical fewer problems as compared with the cell, stable cell for drug development is expected as a source.
In addition, the absorption of the drugs used as a test to provide the intestinal epithelial cells, intestinal stem/progenitor cells from a cell derived from the intestinal tract to rapidly acquire selectively have been reported (patent document 1). In addition, an inhibitor of ALK5 produced using a method not maintain pluripotent cells has been proposed (patent document 2).
  • 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)
  • IWAO Takahiro
  • KABEYA Tomoki
  • MATSUNAGA Tamihide
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 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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