CA2447703A1 - Methods for proliferating terminal differentiated cells and recombinant vectors therefor - Google Patents

Methods for proliferating terminal differentiated cells and recombinant vectors therefor Download PDF

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Publication number
CA2447703A1
CA2447703A1 CA002447703A CA2447703A CA2447703A1 CA 2447703 A1 CA2447703 A1 CA 2447703A1 CA 002447703 A CA002447703 A CA 002447703A CA 2447703 A CA2447703 A CA 2447703A CA 2447703 A1 CA2447703 A1 CA 2447703A1
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cyclin
differentiated cells
dependent kinase
terminal differentiated
cells
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CA002447703A
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CA2447703C (en
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Masaaki Ikeda
Mimi Adachi
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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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4738—Cell cycle regulated proteins, e.g. cyclin, CDC, INK-CCR
    • 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
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/10—Transferases (2.)
    • C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
    • C12N9/1205—Phosphotransferases with an alcohol group as acceptor (2.7.1), e.g. protein kinases
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • 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
    • C12N2501/405—Cell cycle regulated proteins, e.g. cyclins, cyclin-dependant kinases
    • 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
    • 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
    • C12N2510/00—Genetically modified 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
    • C12N2799/00—Uses of viruses
    • C12N2799/02—Uses of viruses as vector
    • C12N2799/021—Uses of viruses as vector for the expression of a heterologous nucleic acid
    • C12N2799/022—Uses of viruses as vector for the expression of a heterologous nucleic acid where the vector is derived from an adenovirus

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Wood Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Cell Biology (AREA)
  • General Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • Cardiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Microbiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Biophysics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Toxicology (AREA)
  • Rheumatology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Enzymes And Modification Thereof (AREA)

Abstract

Terminal differentiated cells are proliferated by introducing a cyclin and a cyclin dependent kinase into the nucleus of said terminal differentiated cells, and then cultivating or holding said cells. In particular, there is provided a method for proliferating terminal differentiated cells comprising adding a nucleotide sequence coding for a nuclear localization signal to at lease one of a cyclin gene and a cyclin dependent kinase gene, and introducing each of said genes to terminal differentiated cells in vitro, and then cultivating said cells, or introducing each of said genes directly to terminal differentiated cells in vivo. Said cyclin is a cyclin that can activate CDK4 or CDK6, and said cyclin dependent kinase is a cyclin dependent kinase that is activated by D-type cyclin. The present invention also provides a recombinant vector used for such a method or a pharmaceutical composition comprising said vector.

Claims (14)

1. A method for proliferating terminal differentiated cells comprising, introducing a cyclin and a cyclin dependent kinase into the nucleus of terminal differentiated cells, and then cultivating or holding said cells.
2. A method for proliferating terminal differentiated cells comprising:

adding a nucleotide sequence coding for a nuclear localization signal to at lease one of a cyclin gene and a cyclin dependent kinase gene; and introducing each of said genes to terminal differentiated cells in vitro, and then cultivating said cells, or introducing each of said genes directly to terminal differentiated cells in vivo.
3. The method of claim 1 or 2, wherein said cyclin is a cyclin that is capable of activating a mammalian CDK4 or CDK6.
4. The method of any one of claims 1 to 3, wherein said cyclin dependent kinase is a cyclin dependent kinase that is activated by cyclin D1, D2 or D3.
5. The method of any one of claims 1 to 4, wherein said terminal differentiated cells are cardiomyocytes, nerve cells, kidney cells, or pancreatic cells.
6. The method of any one of claims 2 to 5, wherein said cyclin gene and said cyclin dependent kinase gene are transferred to the terminal differentiated cells by using an adenovirus vector.
7. A recombinant vector comprising a cyclin gene comprising a nucleotide sequence coding for a nuclear localization signal, or a cyclin dependent kinase gene comprising a nucleotide sequence coding for a nuclear localization signal.
8. A recombinant vector comprising a cyclin gene and a cyclin dependent kinase gene, wherein at least one of said genes is (are) attached with a nucleotide sequence coding for a nuclear localization signal.
9. The recombinant vector of claim 7 or 8, wherein said cyclin is a cyclin that is capable of activating a mammalian CDK4 or CDK6.
10. The recombinant vector of claim 7 or 8, wherein said cyclin dependent kinase is a cyclin dependent kinase that is activated by cyclin D1, D2 or D3.
11. The recombinant vector of any one of claims 7 to 10, further comprising an adenovirus vector.
12. A mammalian cell or tissue that was proliferated by the method of any one of claims 1 to 6.
13. A pharmaceutical composition for proliferating terminal differentiated cells or tissues, comprising an effective amount of the recombinant vector of any one of claims 7 to 11.
14. A method for treating cardiopathy in a human patient comprising directly introducing into myocardium of the patient the pharmaceutical composition of claim 13, and proliferating said myocardium of the patient.
CA2447703A 2001-05-17 2001-09-21 Methods for proliferating terminal differentiated cells and recombinant vectors therefor Expired - Fee Related CA2447703C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
JP2001148266 2001-05-17
JP2001-148266 2001-05-17
PCT/JP2001/008208 WO2002095026A1 (en) 2001-05-17 2001-09-21 Method of proliferating terminal differentiated cells and recombinant vector therefor

Publications (2)

Publication Number Publication Date
CA2447703A1 true CA2447703A1 (en) 2002-11-28
CA2447703C CA2447703C (en) 2011-04-19

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Family Applications (1)

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CA2447703A Expired - Fee Related CA2447703C (en) 2001-05-17 2001-09-21 Methods for proliferating terminal differentiated cells and recombinant vectors therefor

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JP (1) JP4499994B2 (en)
BR (1) BR0117014A (en)
CA (1) CA2447703C (en)
WO (1) WO2002095026A1 (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014038653A1 (en) * 2012-09-07 2014-03-13 国立大学法人京都大学 Production method for kidney-derived somatic stem cells
WO2014038655A1 (en) * 2012-09-07 2014-03-13 国立大学法人京都大学 Method of producing intestinal epithelium-derived somatic stem cells
CN107847523B (en) 2015-04-07 2022-03-11 J·大卫格莱斯顿学会(根据J·大卫格莱斯顿意愿建立的遗嘱信托) Method for inducing cell division of postmitotic cells

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Publication number Publication date
BR0117014A (en) 2004-04-20
JP4499994B2 (en) 2010-07-14
JPWO2002095026A1 (en) 2004-09-09
WO2002095026A8 (en) 2003-03-06
CA2447703C (en) 2011-04-19
WO2002095026A1 (en) 2002-11-28

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