Title:
METHOD FOR PRODUCING MULTINUCLEATED MEGAKARYOCYTE WITH ENHANCED PLATELET PRODUCTION CAPABILITY, METHOD FOR PRODUCING PLATELETS, METHOD FOR PRODUCING PLATELET PREPARATION, AND METHOD FOR PRODUCING BLOOD PREPARATION
Document Type and Number:
WIPO Patent Application WO/2022/265117
Kind Code:
A1
Abstract:
The present invention addresses the problem of providing a method that is capable of improving platelet production. This production method is for producing a multinucleated megakaryocyte with an enhanced platelet production capability, the method comprising a multinucleation step in which, in the presence of a growth factor of a megakaryocyte before multinucleation, a megakaryocyte before multinucleation is multinucleated to induce a multinucleated megakaryocyte. In the multinucleation step, the activity of at least one selected from the group consisting of an aromatic hydrocarbon receptor (AhR), Rho-binding kinase (ROCK), a bispecific tyrosine-phosphorylation regulated kinase (DYRK), and myosin 2 is suppressed, and in the presence of harmine, the megakaryocyte before multinucleation is multinucleated to induce a multinucleated megakaryocyte.
Inventors:
ITO YUKITAKA (JP)
MISUMI SACHIYO (JP)
MISUMI SACHIYO (JP)
Application Number:
PCT/JP2022/024432
Publication Date:
December 22, 2022
Filing Date:
June 17, 2022
Export Citation:
Assignee:
MEGAKARYON CORP (JP)
International Classes:
C12N5/078; A61K35/19; A61P7/04; C12N5/10; C12N15/09
Domestic Patent References:
| WO2021075568A1 | 2021-04-22 | |||
| WO2021117886A1 | 2021-06-17 | |||
| WO2021117900A1 | 2021-06-17 | |||
| WO2011034073A1 | 2011-03-24 | |||
| WO2012157586A1 | 2012-11-22 | |||
| WO2014123242A1 | 2014-08-14 | |||
| WO2012015914A2 | 2012-02-02 |
Foreign References:
| JP2019026591A | 2019-02-21 | |||
| JP2021102068A | 2021-07-15 |
Other References:
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NAKAMURA S ET AL.: "Expandable megakaryocyte cell lines enable clinically applicable generation of platelets from human induced pluripotent stem cells", CELL STEM CELL, vol. 14, no. 4, 2014, pages 535 - 548, XP055567214, DOI: 10.1016/j.stem.2014.01.011
HIDEYUKI OGURO ET AL.: "Senescence and Ageing of Stem Cells Regulated by Polycomb Complexes", REGENERATIVE MEDICINE, vol. 6, no. 4, 2007, pages 26 - 32
JESUS GIL ET AL.: "Regulation of the INK4b-ARF-INK4a tumour suppressor locus: all for one or one for all", NATURE REVIEWS MOLECULAR CELL BIOLOGY, vol. 7, 2007, pages 667 - 677, XP037922534, DOI: 10.1038/nrm1987
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"Genbank", Database accession no. NM_001321309
ISAO KII ET AL.: "Selective inhibition of the kinase DYRKIAby targeting its folding process", NAT. COMMUN., vol. 7, no. 11391, 2016, XP055937382, DOI: 10.1038/ncomms11391
TAKAYAMA N. ET AL.: "Transient activation of c-MYC expression is critical for efficient platelet generation from human induced pluripotent stem cells", J. EXP. MED., vol. 13, no. NM_001145809, 2010, pages 2817 - 2830
YAMAGUCHI ET AL.: "Development of an All-in-One Inducible Lentiviral Vector for Gene Specific Analysis of Reprogramming", PLOS ONE, vol. 7, no. 7, 2012, pages 41007
TAKAYAMA N: "Generation of functional platelets from human embryonic stem cells in vitro via ES-sacs, VEGF-promoted structures that concentrate hematopoietic progenitors", BLOOD, vol. 111, no. 11, 2008, pages 5298 - 5306
NAKAMURA S ET AL.: "Expandable megakaryocyte cell lines enable clinically applicable generation of platelets from human induced pluripotent stem cells", CELL STEM CELL, vol. 14, no. 4, 2014, pages 535 - 548, XP055567214, DOI: 10.1016/j.stem.2014.01.011
HIDEYUKI OGURO ET AL.: "Senescence and Ageing of Stem Cells Regulated by Polycomb Complexes", REGENERATIVE MEDICINE, vol. 6, no. 4, 2007, pages 26 - 32
JESUS GIL ET AL.: "Regulation of the INK4b-ARF-INK4a tumour suppressor locus: all for one or one for all", NATURE REVIEWS MOLECULAR CELL BIOLOGY, vol. 7, 2007, pages 667 - 677, XP037922534, DOI: 10.1038/nrm1987
SOO-HYUN KIM ET AL.: "Absence of pl6INK4a and truncation of ARF tumor suppressors in chickens", PNAS, vol. 100, no. 1, 2003, pages 211 - 216
"Genbank", Database accession no. NM_001321309
ISAO KII ET AL.: "Selective inhibition of the kinase DYRKIAby targeting its folding process", NAT. COMMUN., vol. 7, no. 11391, 2016, XP055937382, DOI: 10.1038/ncomms11391
TAKAYAMA N. ET AL.: "Transient activation of c-MYC expression is critical for efficient platelet generation from human induced pluripotent stem cells", J. EXP. MED., vol. 13, no. NM_001145809, 2010, pages 2817 - 2830
YAMAGUCHI ET AL.: "Development of an All-in-One Inducible Lentiviral Vector for Gene Specific Analysis of Reprogramming", PLOS ONE, vol. 7, no. 7, 2012, pages 41007
Attorney, Agent or Firm:
IP LAW FIRM LEXCEED TECH (JP)
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