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WO2013063305A3 - Directed cardiomyocyte differentiation of stem cells - Google Patents

Directed cardiomyocyte differentiation of stem cells Download PDF

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Publication number
WO2013063305A3
WO2013063305A3 PCT/US2012/061972 US2012061972W WO2013063305A3 WO 2013063305 A3 WO2013063305 A3 WO 2013063305A3 US 2012061972 W US2012061972 W US 2012061972W WO 2013063305 A3 WO2013063305 A3 WO 2013063305A3
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WO
WIPO (PCT)
Prior art keywords
stem cells
cardiomyocytes
cardiac
differentiation system
small molecule
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2012/061972
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French (fr)
Other versions
WO2013063305A2 (en
Inventor
Roger Joseph Hajjar
Ioannis Karakikes
Grant SENYEI
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Icahn School of Medicine at Mount Sinai
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Mount Sinai School of Medicine
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Publication date
Application filed by Mount Sinai School of Medicine filed Critical Mount Sinai School of Medicine
Publication of WO2013063305A2 publication Critical patent/WO2013063305A2/en
Anticipated expiration legal-status Critical
Publication of WO2013063305A3 publication Critical patent/WO2013063305A3/en
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
    • C12N5/0657—Cardiomyocytes; Heart cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2500/00—Specific components of cell culture medium
    • C12N2500/30—Organic components
    • C12N2500/38—Vitamins
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/10—Growth factors
    • C12N2501/155—Bone morphogenic proteins [BMP]; Osteogenins; Osteogenic factor; Bone inducing factor
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/10—Growth factors
    • C12N2501/16—Activin; Inhibin; Mullerian inhibiting substance
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/40—Regulators of development
    • C12N2501/415—Wnt; Frizzeled
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/998—Proteins not provided for elsewhere
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2506/00—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells
    • C12N2506/02—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from embryonic cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2506/00—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells
    • C12N2506/45—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from artificially induced pluripotent stem cells

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Biotechnology (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Genetics & Genomics (AREA)
  • Microbiology (AREA)
  • Cell Biology (AREA)
  • Rheumatology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Cardiology (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

Disclosed is a fully chemically defined, small molecule-mediated, directed differentiation system that promotes differentiation of stem cells, including embryonic stem cells, induced pluripotent stem cells, and adult stem cells, such as human forms of these stem cell types, to ventricular cardiomyocytes in a highly efficient, reproducible and scalable fashion. Molecular characterization revealed the cardiomyocytes' progression through the sequential stages of cardiac fate specification. Phenotypic and electrophysiological analysis illustrated the generation of a highly pure population of cardiomyocytes (greater than 90%) exhibiting the expected physiological characteristics and response to cardioactive compounds. These data indicate that the directed differentiation system, through small molecule-mediated manipulation of developmental signaling pathways, generates a nearly pure population of functional ventricular cardiomyocytes from pluripotent stem cells. The disclosed differentiation system provides a platform to perform large-scale pharmacological screenings and provides a valuable source of cardiac progenitor cells and cardiomyocytes for cell replacement therapies in cardiac repair.
PCT/US2012/061972 2011-10-25 2012-10-25 Directed cardiomyocyte differentiation of stem cells Ceased WO2013063305A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201161551294P 2011-10-25 2011-10-25
US61/551,294 2011-10-25

Publications (2)

Publication Number Publication Date
WO2013063305A2 WO2013063305A2 (en) 2013-05-02
WO2013063305A3 true WO2013063305A3 (en) 2015-06-18

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2012/061972 Ceased WO2013063305A2 (en) 2011-10-25 2012-10-25 Directed cardiomyocyte differentiation of stem cells

Country Status (1)

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WO (1) WO2013063305A2 (en)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK2840132T3 (en) 2013-08-22 2017-02-20 Georg-August-Universität Göttingen Stiftung Öffenlichen Rechts Universitätsmedizin Method of Manufacturing Constructed Heart Muscle (EHM)
JP6681825B2 (en) * 2013-09-20 2020-04-15 レパイロン・ゲーエムベーハーＲｅｐａｉｒｏｎ Ｇｍｂｈ Direct differentiation of pluripotent stem cells into functional myocardium
US10888588B2 (en) 2013-10-18 2021-01-12 Icahn School Of Medicine At Mount Sinai Directed cardiomyocyte differentiation and ventricular specification of stem cells
GB201412554D0 (en) * 2014-07-15 2014-08-27 Cambridge Entpr Ltd In vitro mesodermal differentiation
JP7089484B2 (en) 2016-06-01 2022-06-22 ミルテニイ ビオテック ベー．ファー． ウント コー．カーゲー Methods for Generating, Identifying and Isolating Cardiomyocytes and Cardiomyocyte Subpopulations Derived from Human Pluripotent Stem Cells
CN108048550A (en) * 2017-12-08 2018-05-18 南京医科大学 A kind of Environmental Chemical Pollutants cardiac development toxicity assessment technical method
CN108913655B (en) * 2018-07-16 2022-07-15 浙江大学 Method for establishing human-derived myocardial hypertrophy model based on pluripotent stem cell technology
CN111778205B (en) * 2019-04-04 2022-09-30 青岛百洋智心科技有限公司 Human cardiac muscle cell separation reagent, culture medium, separation method and culture method
GB201908180D0 (en) * 2019-06-07 2019-07-24 Francis Crick Institute Ltd Therapy for heart disorders
CN113337458B (en) * 2021-06-02 2025-11-25 呈诺再生医学科技(珠海横琴新区)有限公司 A method to improve the yield and purity of cardiomyocytes induced by pluripotent stem cells.

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080187494A1 (en) * 2005-09-12 2008-08-07 Es Cell International Pte Ltd Cardiomyocyte Production
US20110097799A1 (en) * 2009-10-19 2011-04-28 Casey Stankewicz Cardiomyocyte production
US20110212061A1 (en) * 2002-05-17 2011-09-01 Mount Sinai School Of Medicine Of New York University Mesoderm and Definitive Endoderm Cell Populations

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110212061A1 (en) * 2002-05-17 2011-09-01 Mount Sinai School Of Medicine Of New York University Mesoderm and Definitive Endoderm Cell Populations
US20080187494A1 (en) * 2005-09-12 2008-08-07 Es Cell International Pte Ltd Cardiomyocyte Production
US20110097799A1 (en) * 2009-10-19 2011-04-28 Casey Stankewicz Cardiomyocyte production

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
BURRIDGE ET AL.: "A Universal System for Highly Efficient Cardiac Differentiation of Human Induced Pluripotent Stem Cells That Eliminates Interline Variability.", PLOS ONE., vol. 6, no. 4, 8 April 2011 (2011-04-08), pages E18293, XP009167975, DOI: doi:10.1371/journal.pone.0018293 *
ZHANG ET AL.: "Dedifferentiation and Proliferation of Mammalian Cardiomyocytes.", PLOS ONE., vol. 5, no. 9, 2010, pages E12559 *

Also Published As

Publication number Publication date
WO2013063305A2 (en) 2013-05-02

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