Title:
METHOD FOR INDUCING DIFFERENTIATION OF PLURIPOTENT STEM CELLS INTO INTESTINAL EPITHELIAL CELLS
Document Type and Number:
WIPO Patent Application WO/2019/156200
Kind Code:
A1
Abstract:
The present invention addresses the problem of providing a novel means whereby cells showing a function more closely similar to the function of intestinal epithelial cells of a living body can be easily and efficiently prepared. According to the present invention, differentiation of pluripotent stem cells into intestinal epithelial cells is induced by: (1) a step for differentiating the pluripotent stem cells into intestinal stem cell-like cells; and (2) a step for differentiating the intestinal stem cell-like cells obtained in step (1) into intestinal epithelial cell-like cells with the combined use of an MEK1 inhibitor, a DNA methylation inhibitor, a TGFβ receptor inhibitor, EGF and a cAMP activator.
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Inventors:
MATSUNAGA TAMIHIDE (JP)
IWAO TAKAHIRO (JP)
KABEYA TOMOKI (JP)
MIMA SHINJI (JP)
MIYASHITA TOSHIHIDE (JP)
IWAO TAKAHIRO (JP)
KABEYA TOMOKI (JP)
MIMA SHINJI (JP)
MIYASHITA TOSHIHIDE (JP)
Application Number:
PCT/JP2019/004553
Publication Date:
August 15, 2019
Filing Date:
February 08, 2019
Export Citation:
Assignee:
UNIV NAGOYA CITY PUBLIC UNIV CORP (JP)
FUJIFILM CORP (JP)
FUJIFILM CORP (JP)
International Classes:
C12N5/071; C12N1/00; C12N5/0735; C12N5/10; C12Q1/02
Domestic Patent References:
| WO2017154795A1 | 2017-09-14 | |||
| WO2014132933A1 | 2014-09-04 | |||
| WO2017154795A1 | 2017-09-14 | |||
| WO2014165663A1 | 2014-10-09 |
Foreign References:
| JP2008206510A | 2008-09-11 | |||
| JP2012511935A | 2012-05-31 |
Other References:
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KODAMA N. ET AL.: "Characteristic Analysis of Intestinal Transport in Enterocyte-Like Cells Differentiated from Human Induced Pluripotent Stem Cells", DRUG METABOLISM AND DISPOSITION, vol. 44, no. 10, 2016, pages 1662 - 1667, XP055629227, DOI: 10.1124/dmd.116.069336
KABEYA T. ET AL.: "Cyclic AMP Signaling Promotes the Differentiation of Human Induced Pluripotent Stem Cells into Intestinal Epithelial Cells", DRUG METABOLISM AND DISPOSITION, vol. 46, no. 10, October 2018 (2018-10-01), pages 1411 - 1419, XP055629232, DOI: 10.1124/dmd.118.082123
UEDA T., BIOCHEM BIOPHYS RES COMMUN., vol. 391, no. 1, 1 January 2010 (2010-01-01), pages 38 - 42
MCCRACKEN K. W., NAT PROTOC., vol. 6, no. 12, 10 November 2011 (2011-11-10), pages 1920 - 8
SPENCE J. R., NATURE, vol. 470, no. 7332, 3 February 2011 (2011-02-03), pages 105 - 109
OGAKI S., STEM CELLS, vol. 31, no. 6, June 2013 (2013-06-01), pages 1086 - 1096
OZAWA T., SCI REP., vol. 5, 12 November 2015 (2015-11-12), pages 16479
OGAKI S., SCI REP., vol. 5, 30 November 2015 (2015-11-30), pages 17297
IWAO T., DRUG METAB PHARMACOKINET, vol. 29, no. 1, 2014, pages 44 - 51
IWAO T., DRUG METAB DISPOS, vol. 43, no. 6, 2015, pages 603 - 610
"Mouse Embryo A Laboratory Manual", 1994, COLD SPRING HARBOR LABORATORY PRESS
CIBELLI ET AL., SCIENCE, vol. 280, 1998, pages 1256 - 1147
WILMUT ET AL., NATURE, vol. 385, 1997, pages 810
IRIYA ET AL., PROTEIN NUCLEIC ACID ENZYME, vol. 44, 1999, pages 892
BAGUISI ET AL., NATURE BIOTECHNOLOGY, vol. 17, 1999, pages 456
WAKAYAMA ET AL., NATURE, vol. 394, 1998, pages 369
NATURE GENETICS, vol. 22, 1999, pages 127
PROC. NATL. ACAD. SCI. USA, vol. 96, 1999, pages 14984
RIDEOUTIII ET AL., NATURE GENETICS, vol. 24, 2000, pages 109
TACHIBANA ET AL.: "Human Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer", CELL, 2013
YU J ET AL., SCIENCE, vol. 318, no. 5858, 2007, pages 1917 - 1920
NAKAJIMA ET AL., STEM CELLS, vol. 25, 2007, pages 983 - 985
KIM ET AL., CELL STEM CELL, vol. 1, 2007, pages 346 - 352
REVAZOVA ET AL., CLONING STEM CELLS, vol. 9, 2007, pages 432 - 449
REVAZOVA ET AL., CLONING STEM CELLS, vol. 10, 2008, pages 11 - 24
STRELCHENKO N. ET AL., REPROD BIOMED ONLINE, vol. 9, 2004, pages 623 - 629
KLIMANSKAYAI. ET AL., NATURE, vol. 444, 2006, pages 481 - 485
CHUNG Y., CELL STEM CELL, vol. 2, 2008, pages 113 - 117
ZHANG X. ET AL., STEM CELLS, vol. 24, 2006, pages 2669 - 2676
WASSARMAN,P. M. ET AL., METHODS IN ENZYMOLOGY, vol. 365, 2003
MATSUI ET AL., CELL, vol. 70, 1992, pages 841 - 847
SHAMBLOTT ET AL., PROC. NATL. ACAD. SCI. USA, vol. 95, no. 23, 1998, pages 13726 - 13731
TURNPENNY ET AL., STEM CELLS, vol. 21, no. 5, 2003, pages 598 - 609
TAKAHASHI KYAMANAKA S, CELL, vol. 126, no. 4, 2006, pages 663 - 676
TAKAHASHI, K ET AL., CELL, vol. 131, no. 5, 2007, pages 861 - 72
NAKAGAWA M ET AL., NAT. BIOTECHNOL., vol. 26, no. 11, 2008, pages 1269 - 1275
KIM J B ET AL., NATURE, vol. 454, no. 7204, 2008, pages 646 - 650
KIM J B ET AL., CELL, vol. 136, no. 3, 2009, pages 411 - 419
KIM DKIM C HMOON J I ET AL., CELL STEM CELL, vol. 4, 2009, pages 472 - 476
SILVA J ET AL., PLOS. BIOL., vol. 6, no. 10, 2008, pages e253
STADTFELD M ET AL., SCIENCE, vol. 322, no. 5903, 2008, pages 949 - 953
WOLTJEN KMICHAEL I PMOHSENI P ET AL., NATURE, vol. 458, 2009, pages 771 - 775
YUSA KRAD RTAKEDA J ET AL., NAT METHODS, vol. 6, 2009, pages 363 - 369
YU JHU KSMUGA-OTTO KTIAN S ET AL., SCIENCE, vol. 324, 2009, pages 797 - 801
CHEMICAL ABSTRACTS, Columbus, Ohio, US; abstract no. 1135306-29-4
TAKENAKA THARADA NKUZE JCHIBA MIWAO TMATSUNAGA T: "Human small intestinal epithelial cells differentiated from adult intestinal stem cells as a novel system for predicting oral drug absorption in humans", DRUG METAB DISPOS, vol. 42, 2014, pages 1947 - 54
TAKENAKA THARADA NKUZE JCHIBA MIWAO TMATSUNAGA T: "Application of a Human Intestinal Epithelial Cell Monolayer to the Prediction of Oral Drug Absorption in Humans as a Superior Alternative to the Caco-2 Cell Monolayer", J PHARM SCI., vol. 105, 2016, pages 915 - 924
TACHIBANA TKATO MSUGIYAMA Y: "Prediction of nonlinear intestinal absorption of CYP3A4 and P-glycoprotein substrates from their in vitro Km values", PHARM RES., vol. 29, 2012, pages 651 - 68
CHONG SDANDO SASOUCEK KMMORRISON RA: "In vitro permeability through caco-2 cells is not quantitatively predictive of in vivo absorption for peptide-like drugs absorbed via the dipeptide transporter system", PHARM RES., vol. 13, 1996, pages 120 - 3
ZHU CJIANG LCHEN TMHWANG KK: "A comparative study of artificial membrane permeability assay for high throughput profiling of drug absorption potential", EUR J MED CHEM., vol. 37, 2002, pages 399 - 407
CHENG KCLI CUSS AS: "Prediction of oral drug absorption in humans-from cultured cell lines and experimental animals", EXPERT OPIN DRUG METAB TOXICOL., vol. 4, 2008, pages 581 - 90
See also references of EP 3750985A4
KODAMA N. ET AL.: "Characteristic Analysis of Intestinal Transport in Enterocyte-Like Cells Differentiated from Human Induced Pluripotent Stem Cells", DRUG METABOLISM AND DISPOSITION, vol. 44, no. 10, 2016, pages 1662 - 1667, XP055629227, DOI: 10.1124/dmd.116.069336
KABEYA T. ET AL.: "Cyclic AMP Signaling Promotes the Differentiation of Human Induced Pluripotent Stem Cells into Intestinal Epithelial Cells", DRUG METABOLISM AND DISPOSITION, vol. 46, no. 10, October 2018 (2018-10-01), pages 1411 - 1419, XP055629232, DOI: 10.1124/dmd.118.082123
UEDA T., BIOCHEM BIOPHYS RES COMMUN., vol. 391, no. 1, 1 January 2010 (2010-01-01), pages 38 - 42
MCCRACKEN K. W., NAT PROTOC., vol. 6, no. 12, 10 November 2011 (2011-11-10), pages 1920 - 8
SPENCE J. R., NATURE, vol. 470, no. 7332, 3 February 2011 (2011-02-03), pages 105 - 109
OGAKI S., STEM CELLS, vol. 31, no. 6, June 2013 (2013-06-01), pages 1086 - 1096
OZAWA T., SCI REP., vol. 5, 12 November 2015 (2015-11-12), pages 16479
OGAKI S., SCI REP., vol. 5, 30 November 2015 (2015-11-30), pages 17297
IWAO T., DRUG METAB PHARMACOKINET, vol. 29, no. 1, 2014, pages 44 - 51
IWAO T., DRUG METAB DISPOS, vol. 43, no. 6, 2015, pages 603 - 610
"Mouse Embryo A Laboratory Manual", 1994, COLD SPRING HARBOR LABORATORY PRESS
CIBELLI ET AL., SCIENCE, vol. 280, 1998, pages 1256 - 1147
WILMUT ET AL., NATURE, vol. 385, 1997, pages 810
IRIYA ET AL., PROTEIN NUCLEIC ACID ENZYME, vol. 44, 1999, pages 892
BAGUISI ET AL., NATURE BIOTECHNOLOGY, vol. 17, 1999, pages 456
WAKAYAMA ET AL., NATURE, vol. 394, 1998, pages 369
NATURE GENETICS, vol. 22, 1999, pages 127
PROC. NATL. ACAD. SCI. USA, vol. 96, 1999, pages 14984
RIDEOUTIII ET AL., NATURE GENETICS, vol. 24, 2000, pages 109
TACHIBANA ET AL.: "Human Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer", CELL, 2013
YU J ET AL., SCIENCE, vol. 318, no. 5858, 2007, pages 1917 - 1920
NAKAJIMA ET AL., STEM CELLS, vol. 25, 2007, pages 983 - 985
KIM ET AL., CELL STEM CELL, vol. 1, 2007, pages 346 - 352
REVAZOVA ET AL., CLONING STEM CELLS, vol. 9, 2007, pages 432 - 449
REVAZOVA ET AL., CLONING STEM CELLS, vol. 10, 2008, pages 11 - 24
STRELCHENKO N. ET AL., REPROD BIOMED ONLINE, vol. 9, 2004, pages 623 - 629
KLIMANSKAYAI. ET AL., NATURE, vol. 444, 2006, pages 481 - 485
CHUNG Y., CELL STEM CELL, vol. 2, 2008, pages 113 - 117
ZHANG X. ET AL., STEM CELLS, vol. 24, 2006, pages 2669 - 2676
WASSARMAN,P. M. ET AL., METHODS IN ENZYMOLOGY, vol. 365, 2003
MATSUI ET AL., CELL, vol. 70, 1992, pages 841 - 847
SHAMBLOTT ET AL., PROC. NATL. ACAD. SCI. USA, vol. 95, no. 23, 1998, pages 13726 - 13731
TURNPENNY ET AL., STEM CELLS, vol. 21, no. 5, 2003, pages 598 - 609
TAKAHASHI KYAMANAKA S, CELL, vol. 126, no. 4, 2006, pages 663 - 676
TAKAHASHI, K ET AL., CELL, vol. 131, no. 5, 2007, pages 861 - 72
NAKAGAWA M ET AL., NAT. BIOTECHNOL., vol. 26, no. 11, 2008, pages 1269 - 1275
KIM J B ET AL., NATURE, vol. 454, no. 7204, 2008, pages 646 - 650
KIM J B ET AL., CELL, vol. 136, no. 3, 2009, pages 411 - 419
KIM DKIM C HMOON J I ET AL., CELL STEM CELL, vol. 4, 2009, pages 472 - 476
SILVA J ET AL., PLOS. BIOL., vol. 6, no. 10, 2008, pages e253
STADTFELD M ET AL., SCIENCE, vol. 322, no. 5903, 2008, pages 949 - 953
WOLTJEN KMICHAEL I PMOHSENI P ET AL., NATURE, vol. 458, 2009, pages 771 - 775
YUSA KRAD RTAKEDA J ET AL., NAT METHODS, vol. 6, 2009, pages 363 - 369
YU JHU KSMUGA-OTTO KTIAN S ET AL., SCIENCE, vol. 324, 2009, pages 797 - 801
CHEMICAL ABSTRACTS, Columbus, Ohio, US; abstract no. 1135306-29-4
TAKENAKA THARADA NKUZE JCHIBA MIWAO TMATSUNAGA T: "Human small intestinal epithelial cells differentiated from adult intestinal stem cells as a novel system for predicting oral drug absorption in humans", DRUG METAB DISPOS, vol. 42, 2014, pages 1947 - 54
TAKENAKA THARADA NKUZE JCHIBA MIWAO TMATSUNAGA T: "Application of a Human Intestinal Epithelial Cell Monolayer to the Prediction of Oral Drug Absorption in Humans as a Superior Alternative to the Caco-2 Cell Monolayer", J PHARM SCI., vol. 105, 2016, pages 915 - 924
TACHIBANA TKATO MSUGIYAMA Y: "Prediction of nonlinear intestinal absorption of CYP3A4 and P-glycoprotein substrates from their in vitro Km values", PHARM RES., vol. 29, 2012, pages 651 - 68
CHONG SDANDO SASOUCEK KMMORRISON RA: "In vitro permeability through caco-2 cells is not quantitatively predictive of in vivo absorption for peptide-like drugs absorbed via the dipeptide transporter system", PHARM RES., vol. 13, 1996, pages 120 - 3
ZHU CJIANG LCHEN TMHWANG KK: "A comparative study of artificial membrane permeability assay for high throughput profiling of drug absorption potential", EUR J MED CHEM., vol. 37, 2002, pages 399 - 407
CHENG KCLI CUSS AS: "Prediction of oral drug absorption in humans-from cultured cell lines and experimental animals", EXPERT OPIN DRUG METAB TOXICOL., vol. 4, 2008, pages 581 - 90
See also references of EP 3750985A4
Attorney, Agent or Firm:
SIKS & CO. (JP)
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