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METHOD FOR INDUCING DIFFERENTIATION OF PLURIPOTENT STEM CELL INTO CARDIAC MUSCLE NEW

外国特許コード F200010106
整理番号 3494
掲載日 2020年5月18日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2013JP051644
国際公開番号 WO 2013111875
国際出願日 平成25年1月25日(2013.1.25)
国際公開日 平成25年8月1日(2013.8.1)
優先権データ
  • 201261591805 (2012.1.27) US
発明の名称 (英語) METHOD FOR INDUCING DIFFERENTIATION OF PLURIPOTENT STEM CELL INTO CARDIAC MUSCLE NEW
発明の概要(英語) The present invention relates to a method for inducing the differentiation of a pluripotent stem cell into a cardiac muscle, comprising the following steps: (1) a step of culturing the pluripotent stem cell in a culture medium containing at least one WNT signal activator; and (2) a step of culturing a cell produced in step (1) in a culture medium containing at least one WNT signal inhibitor.
従来技術、競合技術の概要(英語) BACKGROUND ART
Human pluripotent stem cells (hPSC) (human embryonic stem cell (hESC) and human induced pluripotent stem cell (hiPSC) including) is, grow indefinitely in an undifferentiated state, with the heart to differentiate into many cell types of human tissues can be (non-patent document 1-7). Therefore, hPSC is, in the treatment of heart disease which can be useful for cell-based. Cell-based treatment, functions of the myocardial cells hPSC efficient production is required. The most common currently used method, cytokine of embryoid bodies (for example, DKK1, bFGF, Activin A, and BMP4) and the suspension culture, or mouse END2 (the proximal endoderm-like cells (visceral endoderm) ) co-culture is the removal of the (non-patent document 13,15-17). However, these methods have low efficiencies (production of heart muscle cells 10-50%) (non-patent document 15), animal cells or fetal bovine serum (FBS) in order to use the contamination cannot be avoided and the heterologous component (non-patent document 18), the, the use of recombinant cytokines is cost-effective for large-scale production is not good. Further, by previous studies, induction of heart muscle cells hPSC strains for optimal cytokine concentration is shown to be different from the individual (non-patent document 19) and, this is the optimization of the method indicates if operation is needed. Recently, universal hPSC lines does not depend on the cardiac muscle differentiation method were reported, the method for efficient differentiation FBS and growth factors such as bFGF or BMP4 (non-patent document 20) in need thereof.
Is a low molecular weight compound, unknown factors in the recombinant cytokine or FBS is a strong candidate as an alternative to the (non-patent document 21) and, for the large-scale culture are suitable for creating a chemically defined medium. So far, such as TGF-β WNT signal and signal activates or inhibits the signal transduction pathway (non-patent document 22, 23) for, or in place of the transcription factor to regulate expression of the (non-patent document 24, 25), a low-molecular compound is used. A plurality of small molecule compound, or tested for the promotion of differentiation and screened. BMP signal inhibitor (Dorsomorphin), p38MAPK (SB203580) signal inhibitor, activator WNT (BIO) signal, and WNT signal inhibitor (XAV939, IWR-1, IWP-1, and IWP-3) is, promote myocardial differentiation have been reported (non-patent document 26-32). However, in these processes, even under serum-containing differentiation can only be obtained at a concentration of 10-60% (non-patent document 26-32). Extensive clinical applications, a more efficient differentiation results in a low-molecular compound are required.
  • 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
  • KYOTO UNIVERSITY
  • 発明者(英語)
  • NAKATSUJI, Norio
  • MINAMI, Itsunari
  • UESUGI, Motonari
  • AIBA, Kazuhiro
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 DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IS JP KE KG KM KN KP KR KZ LA LC LK LR LS LT 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 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 ML MR NE SN TD TG
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