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
Application number
PCT/US2012/061972
Other languages
French (fr)
Other versions
WO2013063305A2 (en
Inventor
Roger Joseph Hajjar
Ioannis Karakikes
Grant SENYEI
Original Assignee
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
Publication of WO2013063305A3 publication Critical patent/WO2013063305A3/en

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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

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 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)

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PCT/US2012/061972 WO2013063305A2 (en) 2011-10-25 2012-10-25 Directed cardiomyocyte differentiation of stem cells

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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
ES2615396T3 (en) 2013-08-22 2017-06-07 Georg-August-Universität Göttingen Stiftung Öffentlichen Rechts Universitätsmedizin Method to produce cardiac muscle by engineering (EHM)
EP3047019B1 (en) * 2013-09-20 2019-07-03 Georg-August-Universität Göttingen Stiftung Öffentlichen Rechts Universitätsmedizin A method to direct differentiation of pluripotent stem cells into functional heart muscle
WO2015058117A1 (en) * 2013-10-18 2015-04-23 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
WO2017207576A1 (en) 2016-06-01 2017-12-07 Miltenyi Biotec Gmbh Process for generation, identification and isolation of human pluripotent stem cell-derived cardiomyocytes and cardiomyocyte subpopulations
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
CN113337458A (en) * 2021-06-02 2021-09-03 呈诺再生医学科技(珠海横琴新区)有限公司 Method for improving yield and purity of pluripotent stem cells directionally induced cardiac muscle 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 *

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