JP5982286B2 - 細胞の再プログラミングのための方法とその用途 - Google Patents
細胞の再プログラミングのための方法とその用途 Download PDFInfo
- Publication number
- JP5982286B2 JP5982286B2 JP2012535565A JP2012535565A JP5982286B2 JP 5982286 B2 JP5982286 B2 JP 5982286B2 JP 2012535565 A JP2012535565 A JP 2012535565A JP 2012535565 A JP2012535565 A JP 2012535565A JP 5982286 B2 JP5982286 B2 JP 5982286B2
- Authority
- JP
- Japan
- Prior art keywords
- cells
- cell
- expression
- medium
- msi1
- 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.)
- Active
Links
Images
Classifications
-
- 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
- C12N5/0662—Stem cells
-
- 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
- A61K35/30—Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- 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
- 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
- C12N5/0618—Cells of the nervous system
-
- 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
- C12N5/0618—Cells of the nervous system
- C12N5/0619—Neurons
-
- 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
- C12N5/0618—Cells of the nervous system
- C12N5/0623—Stem 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
- 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
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0647—Haematopoietic stem cells; Uncommitted or multipotent progenitors
-
- 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
- C12N5/0656—Adult fibroblasts
-
- 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
- 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
- C12N5/0662—Stem cells
- C12N5/0667—Adipose-derived stem cells [ADSC]; Adipose stromal stem 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
- 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
- C12N5/0662—Stem cells
- C12N5/0668—Mesenchymal stem cells from other natural sources
-
- 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
- C12N5/0696—Artificially induced pluripotent stem cells, e.g. iPS
-
- 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
- A61K35/48—Reproductive organs
- A61K35/54—Ovaries; Ova; Ovules; Embryos; Foetal cells; Germ cells
- A61K35/545—Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem 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
- C12N2500/05—Inorganic components
- C12N2500/10—Metals; Metal chelators
- C12N2500/20—Transition metals
- C12N2500/24—Iron; Fe chelators; Transferrin
- C12N2500/25—Insulin-transferrin; Insulin-transferrin-selenium
-
- 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
- C12N2501/06—Anti-neoplasic drugs, anti-retroviral drugs, e.g. azacytidine, cyclophosphamide
-
- 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
- C12N2501/065—Modulators of histone acetylation
-
- 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
- C12N2501/105—Insulin-like growth factors [IGF]
-
- 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
- C12N2501/11—Epidermal growth factor [EGF]
-
- 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
- C12N2501/115—Basic fibroblast growth factor (bFGF, FGF-2)
-
- 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
- C12N2501/13—Nerve growth factor [NGF]; Brain-derived neurotrophic factor [BDNF]; Cilliary neurotrophic factor [CNTF]; Glial-derived neurotrophic factor [GDNF]; Neurotrophins [NT]; Neuregulins
-
- 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
- C12N2501/30—Hormones
- C12N2501/38—Hormones with nuclear receptors
- C12N2501/395—Thyroid hormones
-
- 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
- C12N2501/60—Transcription factors
-
- 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
- C12N2501/60—Transcription factors
- C12N2501/602—Sox-2
-
- 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
- C12N2501/60—Transcription factors
- C12N2501/604—Klf-4
-
- 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
- C12N2501/70—Enzymes
- C12N2501/72—Transferases (EC 2.)
- C12N2501/727—Kinases (EC 2.7.)
-
- 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
- C12N2506/09—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from epidermal cells, from skin cells, from oral mucosa cells
- C12N2506/094—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from epidermal cells, from skin cells, from oral mucosa cells from keratinocytes
-
- 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
- C12N2506/11—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from blood or immune system 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
- C12N2506/13—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from connective tissue cells, from mesenchymal cells
- C12N2506/1307—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from connective tissue cells, from mesenchymal cells from adult fibroblasts
-
- 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
- C12N2506/13—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from connective tissue cells, from mesenchymal cells
- C12N2506/1346—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from connective tissue cells, from mesenchymal cells from mesenchymal stem 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
- C12N2506/13—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from connective tissue cells, from mesenchymal cells
- C12N2506/1346—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from connective tissue cells, from mesenchymal cells from mesenchymal stem cells
- C12N2506/1384—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from connective tissue cells, from mesenchymal cells from mesenchymal stem cells from adipose-derived stem cells [ADSC], from adipose stromal stem 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
- C12N2513/00—3D culture
-
- 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
- C12N5/0676—Pancreatic cells
Description
本願は、参照によりその全体が本明細書に組み込まれているものとみなす、2009年10月31日に出願された米国仮出願第61/256,967号に優先権を主張するものである。
本発明は、真核細胞再プログラミングの分野に関し、特に細胞退行分化に関する。本発明はまた、ヒト体細胞(及び他の細胞)からの安定な神経幹様細胞(NSLCs)を発生させる方法と、そのように発生された細胞のヒトの治療における用途に関する。
従来より、医療、科学、及び診断分野において、卵母細胞又は他の幹細胞と融合又は交換されることなく、容易に取得可能な細胞を一般的に取得が困難である細胞へと再プログラムする、或いは細胞が新しい又は異なる機能性を有するように細胞を再プログラムするための要望がある。
神経幹様細胞(NSLC)
用語の意味
シグナル配列は、ポリペプチドをコ-ド化する核酸配列の5’末端に配置されることが好ましい。「シグナルペプチド」とは、シグナル配列の翻訳から生じたペプチド配列を意味する。
細胞形質転換
神経幹様細胞(NSLCs)の取得
ポリヌクレオチドの送達
ポリペプチドの送達
細胞及び細胞系
組織
スクリ-ニング法
(i)実施例1のように、繊維芽細胞のセッティングを行い、培養し、NSLCに形質転換し、
(ii)別個のウェル中で、Msi1、Ngn2及び/又はMBD2をそれぞれの候補化合物と置き換えることによって、化合物のライブラリをスクリ-ングし、
(iii)候補化合物が繊維芽細胞をNSLCsに形質転換することが、置き換えられたMsi1、Ngn2及び/又はMBD2と同程度に可能である場合、化合物「ヒット」を同定し、
(iv)(iii)部分からの化合物が全てのMsi1、Ngn2及びMBD2を置換せず、並びにそれ自体によって繊維芽細胞をNSLCsへ形質転換することができない場合、次に(iii)からの化合物をそれぞれのウェルに入れることによって、(ii)部分では除去されていなかったMsi1、Ngn2及び/又はMBD2を、異なるウェル中のそれぞれの候補化合物で置き換えることによって化合物のライブラリを測定すること、
(v)(iii)部分からの化合物と一緒に、候補化合物が、置換されたMsi1、Ngn2及び/又はMBD2とほぼ同程度に繊維芽細胞をNSLCsへと形質転換させることが可能な場合、化合物「ヒット」を同定し、
(vi)(v)部分からの化合物がMsi1、Ngn2及び/又はMBD2の全てを置換せず、並びに(iii)部分からの化合物と一緒に繊維芽細胞をNSLCsへと形質転換することができない場合、次いで(iii)及び(v)部分からの化合物をそれぞれのウェルに入れることによって、(ii)部分では除去されていなかったMsi1、Ngn2又はMBD2を異なるウェルにて、それぞれの候補化合物で置き換えることによって、化合物のライブラリをスクリ-ニングし、
(vii)(iii)及び(v)部分からの化合物と共に、置換されたMsi1、Ngn2及び/又はMBD2とほぼ同程度に、候補化合物が繊維芽細胞をNSLCsへと形質転換できる場合、化合物「ヒット」を同定し、
(viii)(iii)、(v)及び(vii)部分からの化合物の組み合わせが繊維芽細胞をNSLCへ形質転換させることができるような場合、これらの化合物に対する修正が行われ得、これらの化合物のより有効かつ安全な変型を更にスクリ-ニングする。
神経栄養因子の送達
実施例
実施例I
ヒト繊維芽細胞の調製
構築されたベクタ-を使用するリポフェクタミンによるHFFの一過性トランスフェクション
遺伝子アレイ解析
実施例II
3つの異なる神経原性遺伝子の再プログラミング効率の比較
遺伝子発現解析
免疫組織化学アッセイ
実施例III
ベクタ-の種々の組み合わせによるHFFのトランスフェクション及び細胞骨格の崩壊
遺伝子発現解析
遺伝子アレイ解析
接着及び浮遊条件中のNSLCへのHFFの再プログラミングにおけるNucleofector II DeviceとNucleofector 96-well Shuttle Deviceの比較
神経球形成アッセイ及び細胞分化アッセイ
実施例VI
HFFsの再プログラミングにおけるBMP信号伝達経路の意味
HFF細胞から産生されたNSLCsは皮膚由来前駆体(SKPs)ではない
実施例VIII
神経様細胞(NLCs)からのBDNF放出
実施例IX
NSLCsに向かう異なる細胞型の再プログラミング
ヒトCD34+細胞、ヒトADSC及びヒト角化細胞の調製
実施例X
3D細胞外マトリックス(CDM)の組立て
CDM内における細胞の分化形質転換及び再プログラミング
実施例XI
CDM内の再プログラムされた細胞遺伝子発現解析
遺伝子発現アレイ
リポフェクタミン及びヌクレオフェクチンによるCDM内の細胞の再プログラミング
遺伝子発現解析
実施例XIII
NSLCsのテロメラ-ゼ活性
実施例XIV
腫瘍形成アッセイ
たが、但しhNPCsに関しては、十分な細胞の欠乏のために、5,000細胞/ウェルにみで再懸濁させた。細胞を、1.2%寒天溶液、2×DMEM/20%PBS、及び細胞懸濁液(1:1:1)で混合し、混合物の75μlを、固化された寒天基層を既に含有するウェルに移し、次いで4℃にて15分間放置し、細胞寒天層を固化させた。増殖培地(StemCell Technologies)100μlを添加し、プレ-トを37℃、5%CO2にて8日間インキュベ-トし、可溶化し溶解させて、蛍光平板読み取り機、CyQuant(登録商標)GR染色剤によって検出された。485/538nmフィルタ-を備えたFlexstation(登録商標)(Molecular Devices)を使用して、蛍光測定が実施された。
実施例XVI
一過性トランスフェクションからのNSLCs中におけるプラスミドDNAの非ゲノム組込み
実施例XVII
移植されたhNSLCsの神経保護的効果
1)多発性硬化症の動物モデルにおける効果
細胞の有無でのEAE動物モデルの処置
2)片麻痺性動物モデル(成人ラットの左感覚運動皮質の片側性アブレ-ション)における効果
実施例XVIII
Shuttle装置及び内胚葉系中胚葉への再プログラミングのための異なる小分子を使用した遺伝子の種々の組み合わせによるHFFのトランスフェクション
膵臓プロジェニタ-様細胞へのHFFsの再プログラミング
実施例XIX
多分可能様幹細胞(PLSC)へのヒト脂肪細胞由来幹細胞(ADSC)の再プログラミング
表34:プラスミド及び1日〜14日の培地構成成分
Matrigel(BD Biosciences)でコ-ティングされた6-ウェルプレ-トに細胞を播種し、37℃、5%CO2にてインキュベ-トされた。1日目及び2日目に、VPA及び5-AZAを補充された又は補充されていない100%mTwSR1培地(StemCell Technologies)に交換された。3日目及び6日目に、それぞれの条件からの細胞が、TrypLE中で5分間インキュベ-トすることによって脱着され、計測並びに遠心分離が行われた。細胞が上記のように再トランスフェクトされて、VPA及び5-AZA有無のmTeSR1培地中、Matrigelコ-ティングプレ-トに播種された。1日〜2日に記載されたように、培地が交換された。潜在能力を持つ再プログラムされた細胞の生存及びクロ-ン増殖を推進するために、Y27632(Stemgent、10μM)が7日〜14日に補充された。20日目に、アルカリフォスファタ-ゼ検出キット(Millipore)を使用して並びに免疫組織化学解析によって、細胞が解析された。
多分可能性へのNSLCsの再プログラミング
実施例XX
SCIDマウスにおける奇形腫アッセイ
参考文献
R, Lane EL, Dunnet SB, Rosser AE.Human
stem cells for CNSrepair.Cell Tissue Res.2008;331(1):301-22.
Mimeault,
M., Hauke, R. & Batra, S. K. 2007. Stem cells: a revolution in therapeutics-recent
advances in stem cell biology and their therapeutic applications in
regenerative medicine and cancer therapies. Clin Pharmacol Ther,82, 252-64.
Levesque,
MF and Neuman T. Transdiffentiation of transfected epidermal basal cells into
neural progenitor cells, neuronal cells and/or glial cells. Patent, filling
date 2000.
Shea
TB. Neuritogenesis in mouse NB2a/d1 neuroblastoma cells: triggering by calcium
influx and involvement of actin and tubulin dynamics. Cell Biol Int Rep.
1990;14(11):967-79.
Yeomans ND, Trier JS, Moxey PC, and
Markezin ET. Maturation and differentiation of cultured fetal stomach. Effects
of corticosteroids, pentagastrin, and cytochalasin B. Gasteroenterology 1976;71(5):770-7.
Paterson
FC, Rudland PS. Microtubule-disrupting drugs increase the frequency of
conversion of a rat mammary epithelial stem cell line to elongated,
myoepithelial-like cells in culture. J Cell Phsiol. 1985;125(1):135-50.
Bouwens
L. Transdifferentiation versus stem cell hypothesis for the regeneration of
islet beta-cells in the pancreas. Micro Res Tech. 1998;43(4):332-6.
Bouwens
L. Cytokeratins and cell differentiation in the pancreas. J Pathol.
1998b;184(3):234-9.
Theise ND,
Nimmakayalu M, Gardner R, Illei PB, Morgan G, Teperman L, Henegariu O, Krause
DS. Liver from bone marrow in humans.
Hepatology 2000;32(1):11-6.
Woodbury
D, Schwarz EJ, Prockop DJ, Black IB. Adult rat and human bone marrow stromal
cells differentiate into neurons. J Neurosci Res. 2000;61(4):364-70.
Brunet,
JF; Ghysen, A. Deconstructing cell determination: proneural genes and neuronal
identity. Bioessays. 1999;21:313-318.
Bertrand
N, Castro DS, and Guillemot F. Proneural
genes and the specification of neural cell types. Nat Rev Neurosci. 2002;3(7):517-30.
McCormick
MB, Tamimi RM, Snider L, Asakura A, Bergstrom D, Tapscott SJ. NeuroD2 and neuroD3: distinct expression
patterns and transcriptional activation potentials within the neuroD gene family.
Mol Cell Biol. 1996;16(10):5792-800.
Guillemot
F, Lo LC, Johnson JE, Auerbach A, Anderson DJ, Joyner Al. Mammalian achaete-scute
homolog 1 is required for the early development of olfactory and autonomic
neurons. Cell 1993;75(3):463-76.
Fode
C, Gradwohl G, Morin X, Dierich A, LeMeur M, Goridis C, Guillemot F. The bHLH
protein NEUROGENIN 2 is a determination factor for epibranchial placode-derived
sensory neurons. Neuron 1998;20(3):483-94.
Fernandes
KJL, McKenzie IA, Mill P, Smith KM, Akhavan M, Barnabe-Heider F, Biernaskie J, Junek A, et al. A dermal
niche for multipotent adult skin-derived precursor cells. Nature Cell Biology 2004;6:1082-1093.
Jacobsen
F, Hirsch T, Mittler D, Schulte M, Lehnhardt M, Druecke D, Homann HH, Steinau
HU, Steinstraesser L.Polybrene improves transfection efficacy of recombinant
replication-deficient adenovirus in cutaneous cells and burned skin. J Gene
Med. 2006;8(2):138-46.
Kearns
CM, Gash DM. GDNF protects nigral dopamine neurons against 6-hydroxydopamine in
vivo. Brain Res. 1995;672(1-2):104-11.
Gash
DM, Zhang Z, Ovadia A, Cass WA, Yi A, Simmerman L, Russel D, Martin D, Lapchak
PA, Collins F, Hoffer BJ, Gerhardt GA. Functional
recovery in parkinsonian monkeys treated with GDNF.Nature
1996;380(6571):252-5.
Lindner
MD, Winn SR, Baetge EE, Hammang JP, Gentile FT, Doherty E, McDermott PE,
Frydel B, Ullman MD, Schallert T et al.
Implantation of encapsulated catecholamine and GDNF-producing cells in rats
with unilateral dopamine depletions and parkinsonian symptoms. Exp Neurol.
1995;132(1):62-76.
Kordower
JH, Emborg ME, Bloch J, Ma SY, Chu Y, Leventhal L, McBride J, Chen EY, Palfi S,
Roitberg BZ, Brown WD, Holden JE, et al.
Neurodegeneration prevented by
lentiviral vector delivery of GDNF in primate models of Parkinson's disease.
Science 2000;290(5492):767-73.
Martinez-Serrano
A, Bjorklund A. Immortalized neural progenitor cells for CNS gene transfer and
repair. Trends Neurosci. 1997;20(11):530-8.
Chambers
SM, Fasano CA, Papapetrou EP, Tomishima M, Sadelain M,
Studer L. Highly efficient neural
conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat
Biotechnol. 2009;27(3):275-80.
Claims (12)
- 繊維芽細胞、角化細胞、血液細胞または骨髄細胞から選択される第1の型の細胞を多能性または単分化能性細胞である神経系細胞へと再プログラミングする方法であって、
(1)前記第1の型の細胞に、少なくとも1種の再プログラミング剤を一過性的に適用することであって、前記再プログラミング剤がクロマチン及び/又はDNAの直接的または間接的な再構築ならびに少なくとも1種の遺伝子調節因子の内因性発現を誘導し、前記少なくとも1種の遺伝子調節因子の内因性発現は前記異なる型の所望の細胞の存在に必要である、適用することと、
(2)前記遺伝子調節因子を安定に発現させることと、
(3)複数の第2の遺伝子を安定して発現させることであって、前記第2の遺伝子の安定な発現は前記遺伝子調節因子が安定に発現した結果であり、(i)前記複数の第2の遺伝子の安定な発現が前記所望の細胞の表現型的及び/又は機能的特性の特徴であり、かつ(ii)前記第2の遺伝子のうちの少なくとも1種の安定な発現が胚幹細胞の表現型的及び機能的特性の特徴ではない、発現させることと、
を含み、
前記再プログラミング剤が、Musashi1(Msi1)及びメチル-CpG結合ドメイン蛋白質2(MBD2);Neurogenin2(Ngn2)及びMBD2;Msi1、Ngn2及びMBD2;ならびにMsi1、Ngn2、5−AzaおよびVPA;からなる群から選択される、
方法。 - ステップ(1)が、前記所望の細胞の形質転換を支援するための条件中に細胞を配置することと、前記再プログラミング剤の不在下において前記遺伝子調節因子を安定に発現させるために十分な期間、前記再プログラミング剤の細胞内レベルを維持することと、を含み、および
ステップ(3)が、前記複数の第2の遺伝子を安定に発現させるために十分な期間、前記所望の細胞の形質転換を支援する培養条件に細胞を維持することを含み、それにより、前記期間の最終にて、前記第1の型の細胞が前記異なる型の所望の細胞へ形質転換される、
請求項1に記載の方法。 - 前記第1の型の細胞のクロマチン及び/又はDNAを、前記細胞のクロマチン及び/又はDNAを再構築する薬剤と接触させることを更に含み、
前記クロマチン及び/又はDNAを再構築する薬剤が、ヒストンアセチル化剤、ヒストン脱アセチル化の阻害剤、DNA脱メチル化剤、DNAメチル化の阻害剤及びそれらの組み合わせからなる群から選択される、請求項1または2に記載の方法。 - 前記神経系細胞が、その後、体細胞に分化される多能性細胞である、請求項1または2に記載の方法。
- 前記神経系細胞が、前記第1の型の細胞中で発現される複数種の遺伝子の安定した抑制によって特徴付けられる、請求項1〜4のいずれか1項に記載の方法。
- 前記再プログラミング剤が細胞内に送達される、請求項1〜5のいずれか一項に記載の方法。
- 前記神経系細胞が、ネスチン、Sox2、GFAPおよびMsi1のうちの1種以上を発現する神経幹様細胞;ならびにβIII−チューブリン、Map2b、シナプシンおよびACHEのうちの1種以上を発現する神経様細胞からなる群から選択される、請求項2〜6のいずれか1項に記載の方法。
- 前記再プログラミング剤が、Musashi1(Msi1)ポリペプチド及びメチル-CpG結合ドメイン蛋白質2(MBD2)ポリペプチド;Neurogenin2(Ngn2)ポリペプチド及びメチル-CpG結合ドメイン蛋白質2(MBD2)ポリペプチド;または、Musashi1(Msi1)ポリペプチド、Neurogenin2(Ngn2)ポリペプチド及びメチル-CpG結合ドメイン蛋白質2(MBD2)ポリペプチド、を発現させる発現ベクターである、請求項1〜7のいずれか1項に記載の方法。
- 前記神経系細胞が、以下の特性:
(i)自己再生または増殖する能力(最終的に分化した体細胞の場合を除く);
(ii)癌性細胞ではないこと;
(iii)安定であり、かつ強制的遺伝子発現又は同様な手段によって人工的に維持されないこと;
(iv)プロジェニター細胞、前駆体細胞、体細胞、ならびに同一の系統のより分化した別の細胞型、のうちの少なくとも1種へと分化できること;
(v)インビボにおいて、制御されない成長、奇形腫形成、及び腫瘍形成を表さないこと、
の全てを有する、請求項8に記載の方法。 - 前記再プログラミング剤が、Musashi1(Msi1)ポリペプチド、Neurogenin2(Ngn2)ポリペプチド及びメチル-CpG結合ドメイン蛋白質2(MBD2)ポリペプチドを発現させる発現ベクターであり、
前記神経系細胞が、Sox2、ネスチン、GFAP、Msi1、およびNgn2からなる群から選択される1種以上の神経幹細胞マーカーを発現し、
前記神経系細胞が、神経特異的チューブリン、微小管関連蛋白質2、NCAM、及び神経伝達物質のためのマーカーからなる群から選択される少なくとも1種の神経特異的抗原を発現し、
前記神経系細胞が、全能性または多分化能性の系列ではなく、およびインビボにおいて腫瘍形成または奇形腫形成を示さない、
請求項1〜9のいずれか1項に記載の方法。 - 前記神経系細胞が、以下の特性:
(i)前記第1の型の細胞の特徴である少なくとも1種のマーカーならびに前記神経系細胞の特徴である少なくとも1種のマーカーを発現すること;
(ii)数ヶ月間自己再生する能力;
(iii)癌性細胞ではないこと;
(iv)安定であり、かつ強制的遺伝子発現又は同様な手段によって人工的に維持されないこと;
(v)プロジェニター細胞、前駆体細胞、体細胞または同一の系統のより分化した別の細胞型のうちの少なくとも1種へと分化できること;
(vi)インビボにおいて、制御されない成長、奇形腫形成、及び腫瘍形成を表さないこと;および
(vii)SCIDマウスにおける奇形腫成長について陰性であること、
の全てを有する多能性細胞である、
請求項1〜9のいずれか1項に記載の方法。 - 前記神経系細胞が、CNS変性またはCNS損傷の治療における使用のためのものである、請求項10または11に記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US25696709P | 2009-10-31 | 2009-10-31 | |
US61/256,967 | 2009-10-31 | ||
PCT/CA2010/001727 WO2011050476A1 (en) | 2009-10-31 | 2010-11-01 | Methods for reprogramming cells and uses thereof |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016059620A Division JP2016146841A (ja) | 2009-10-31 | 2016-03-24 | 細胞の再プログラミングのための方法とその用途 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2013509159A JP2013509159A (ja) | 2013-03-14 |
JP5982286B2 true JP5982286B2 (ja) | 2016-08-31 |
Family
ID=43921216
Family Applications (5)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012535565A Active JP5982286B2 (ja) | 2009-10-31 | 2010-11-01 | 細胞の再プログラミングのための方法とその用途 |
JP2016059620A Pending JP2016146841A (ja) | 2009-10-31 | 2016-03-24 | 細胞の再プログラミングのための方法とその用途 |
JP2018127585A Pending JP2018183152A (ja) | 2009-10-31 | 2018-07-04 | 細胞の再プログラミングのための方法とその用途 |
JP2020082207A Pending JP2020124219A (ja) | 2009-10-31 | 2020-05-07 | 細胞の再プログラミングのための方法とその用途 |
JP2022097154A Active JP7407865B2 (ja) | 2009-10-31 | 2022-06-16 | 細胞の再プログラミングのための方法とその用途 |
Family Applications After (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016059620A Pending JP2016146841A (ja) | 2009-10-31 | 2016-03-24 | 細胞の再プログラミングのための方法とその用途 |
JP2018127585A Pending JP2018183152A (ja) | 2009-10-31 | 2018-07-04 | 細胞の再プログラミングのための方法とその用途 |
JP2020082207A Pending JP2020124219A (ja) | 2009-10-31 | 2020-05-07 | 細胞の再プログラミングのための方法とその用途 |
JP2022097154A Active JP7407865B2 (ja) | 2009-10-31 | 2022-06-16 | 細胞の再プログラミングのための方法とその用途 |
Country Status (17)
Country | Link |
---|---|
US (7) | US9528087B2 (ja) |
EP (2) | EP2494039B1 (ja) |
JP (5) | JP5982286B2 (ja) |
KR (3) | KR102014977B1 (ja) |
AU (3) | AU2010312240B2 (ja) |
BR (1) | BR112012009921B1 (ja) |
CA (1) | CA2779310C (ja) |
DK (1) | DK2494039T3 (ja) |
ES (1) | ES2739672T3 (ja) |
HR (1) | HRP20191213T1 (ja) |
IL (3) | IL219453A (ja) |
LT (1) | LT2494039T (ja) |
MX (1) | MX353245B (ja) |
SG (1) | SG10201702120VA (ja) |
SI (1) | SI2494039T1 (ja) |
WO (1) | WO2011050476A1 (ja) |
ZA (1) | ZA201203902B (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2016146841A (ja) * | 2009-10-31 | 2016-08-18 | ニュー・ワールド・ラボラトリーズ・インコーポレイテッドNew World Laboratories Inc. | 細胞の再プログラミングのための方法とその用途 |
Families Citing this family (67)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7642091B2 (en) | 2005-02-24 | 2010-01-05 | Jau-Nan Lee | Human trophoblast stem cells and use thereof |
US9453205B2 (en) | 2009-10-31 | 2016-09-27 | Genesis Technologies Limited | Methods for reprogramming cells and uses thereof |
JP6002581B2 (ja) * | 2010-02-05 | 2016-10-05 | オークランド ユニサービシズ リミテッドAuckland Uniservices Limited | 細胞プログラミング |
CN109536438A (zh) | 2010-11-15 | 2019-03-29 | 艾克塞利瑞提德生物技术公司 | 由人类滋养层干细胞生成神经干细胞 |
KR20140063501A (ko) | 2010-12-22 | 2014-05-27 | 페이트 세러퓨틱스, 인코포레이티드 | 단세포 분류 및 iPSC의 증강된 재프로그래밍을 위한 세포 배양 플랫폼 |
KR101376635B1 (ko) * | 2011-01-14 | 2014-03-24 | 한국생명공학연구원 | Rex1을 포함하는 세포 리프로그래밍 조성물 및 이를 이용한 유도만능줄기세포 제조방법 |
US20140289882A1 (en) * | 2011-07-19 | 2014-09-25 | Oregon Health And Science University | Compositions and methods for re-programming cells without genetic modification for repairing cartilage damage |
US20130224782A1 (en) * | 2012-02-29 | 2013-08-29 | Chenzhong Kuang | Neurogenesis screening method and system using adipose tissue derived stem cells |
US9428730B2 (en) | 2012-02-29 | 2016-08-30 | Mead Johnson Nutrition Company | Coatings and culture media for promoting neurogenesis in adipose tissue derived stem cells |
GB201118964D0 (en) * | 2011-11-03 | 2011-12-14 | Ucl Business Plc | Method |
KR102029391B1 (ko) * | 2011-12-13 | 2019-11-08 | 유니사 벤쳐스 피티와이 엘티디 | 다능성 줄기세포의 제조방법 |
CN102604894B (zh) * | 2012-02-29 | 2014-07-30 | 中国科学院广州生物医药与健康研究院 | 用于制备神经干细胞的培养基及其用途 |
WO2013138368A1 (en) * | 2012-03-12 | 2013-09-19 | Loma Linda University Medical Center | Substances and methods for the treatment of cerebral amyloid angiopathy related conditions or diseases |
CN104870634A (zh) | 2012-07-19 | 2015-08-26 | 宾夕法尼亚州研究基金会 | 再生用于在神经系统中治疗疾病和损伤的功能性神经元 |
US20140134139A1 (en) * | 2012-11-07 | 2014-05-15 | Northwestern University | Cd34+ cells and methods of use |
CN105143445B (zh) | 2012-11-29 | 2020-07-07 | 宝生物欧洲公司 | 衍生自人多能干细胞的肝细胞样细胞的成熟 |
WO2014085493A1 (en) | 2012-11-30 | 2014-06-05 | Jau-Nan Lee | Methods of differentiating stem cells by modulating mir-124 |
EP3556215A1 (en) * | 2012-12-14 | 2019-10-23 | Celularity, Inc. | Anoikis resistant placental stem cells and uses thereof |
US9982232B2 (en) * | 2012-12-17 | 2018-05-29 | John PIMANDA | Methods of generating cells with multilineage potential |
JP2016513974A (ja) * | 2013-03-14 | 2016-05-19 | チルドレンズ メディカル センター コーポレーション | 造血幹細胞系列を初期化するための組成物および方法 |
NZ713219A (en) | 2013-03-14 | 2017-04-28 | Massachusetts Inst Technology | Compositions and methods for epithelial stem cell expansion and culture |
WO2014170488A1 (en) * | 2013-04-19 | 2014-10-23 | Universita' Degli Studi Di Milano | Methods for the conversion of somatic cells into pancreatic-hormone secreting cells |
KR101655383B1 (ko) | 2013-07-27 | 2016-09-08 | 고려대학교 산학협력단 | 소분자 화합물을 포함하는 만능성 줄기세포의 염색체 안정성 유지용 조성물 |
CA2926372C (en) * | 2013-10-10 | 2023-09-26 | Mcmaster University | Diagnosis and monitoring of endometriosis through bdnf and full-length ntrk2 levels |
US20160298080A1 (en) | 2013-12-03 | 2016-10-13 | The Johns Hopkins University | Method for highly efficient conversion of human stem cells to lineage-specific neurons |
US9512406B2 (en) | 2013-12-20 | 2016-12-06 | The J. David Gladstone Institute, a testamentary trust established under the Will of J. David Gladstone | Generating hepatocytes |
FR3016372B1 (fr) * | 2014-01-13 | 2018-01-19 | Centre Leon Berard | Procede de preparation de cellules pluripotentes induites |
EP3099786A1 (en) * | 2014-01-29 | 2016-12-07 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) | Trans-differentiation of differentiated cells |
EP3604499A1 (en) | 2014-03-04 | 2020-02-05 | Fate Therapeutics, Inc. | Improved reprogramming methods and cell culture platforms |
US20150353623A1 (en) * | 2014-04-03 | 2015-12-10 | Loma Linda University | Substances and methods for the treatment of cerebral amyloid angiopathy related conditions or diseases |
US9259357B2 (en) | 2014-04-16 | 2016-02-16 | Loma Linda University | Composition, preparation, and use of chitosan shards for biomedical applications |
KR101731624B1 (ko) * | 2014-07-01 | 2017-05-04 | 광주과학기술원 | 세포 리프로그래밍 유도용 조성물 |
CN107073042A (zh) | 2014-09-03 | 2017-08-18 | 布里格海姆妇女医院公司 | 用于产生内耳毛细胞来治疗听力损失的组合物、系统和方法 |
CN107208045B (zh) | 2014-11-25 | 2018-11-02 | 宾州研究基金会 | 人神经胶质细胞转化成用于大脑和脊髓修复的神经细胞的化学重编程 |
WO2016086132A1 (en) | 2014-11-26 | 2016-06-02 | Accelerated Biosciences Corp. | Induced hepatocytes and uses thereof |
MA41296A (fr) * | 2014-12-30 | 2017-11-07 | Orgenesis Ltd | Procédés de transdifférenciation et procédés d'utilisation de ceux-ci |
KR20170007181A (ko) | 2015-07-10 | 2017-01-18 | 3스캔 인크. | 조직학적 염색제의 공간 다중화 |
CN105062953A (zh) * | 2015-08-06 | 2015-11-18 | 深圳爱生再生医学科技有限公司 | 三维诱导间充质干细胞转化为胰岛细胞的方法 |
JP7263005B2 (ja) | 2015-10-16 | 2023-04-24 | フェイト セラピューティクス,インコーポレイテッド | 基底状態の多能性の誘導及び維持に関するプラットフォーム |
EP3400286A1 (en) | 2016-01-08 | 2018-11-14 | Massachusetts Institute Of Technology | Production of differentiated enteroendocrine cells and insulin producing cells |
CN116763942A (zh) | 2016-02-18 | 2023-09-19 | 宾州研究基金会 | 脑内生成gaba能神经元 |
US10213511B2 (en) | 2016-03-02 | 2019-02-26 | Frequency Therapeutics, Inc. | Thermoreversible compositions for administration of therapeutic agents |
US11260130B2 (en) | 2016-03-02 | 2022-03-01 | Frequency Therapeutics, Inc. | Solubilized compositions for controlled proliferation of stem cells / generating inner ear hair cells using a GSK3 inhibitor: IV |
US10201540B2 (en) | 2016-03-02 | 2019-02-12 | Frequency Therapeutics, Inc. | Solubilized compositions for controlled proliferation of stem cells / generating inner ear hair cells using GSK3 inhibitors: I |
EP3483262B1 (en) * | 2016-06-03 | 2021-11-17 | Institue of Transfusion Medicine, Academy of Military Medical Sciences, People's Liberation Army of China | Small molecule compound combination for reprogramming digestive tract derived epithelial cells to endodermal stem/progenitor cells, reprogramming method and application |
CN105861447B (zh) * | 2016-06-13 | 2017-12-19 | 广州市搏克生物技术有限公司 | 一种非病毒iPSCs诱导组合物及其试剂盒 |
CN109661582B (zh) | 2016-06-20 | 2023-05-23 | 创始科技有限公司 | 自动化细胞处理系统和方法 |
KR20190104359A (ko) | 2016-12-30 | 2019-09-09 | 프리퀀시 테라퓨틱스, 인크. | 줄기/전구체 지지 세포의 자가 재생을 유도하기 위한 1h-피롤-2,5-다이온 화합물 및 이의 사용 방법 |
US20190352604A1 (en) * | 2017-02-24 | 2019-11-21 | Koji Tanabe | Nerve cell production method |
CN108531453B (zh) * | 2017-03-01 | 2020-12-18 | 中国科学院动物研究所 | 一种将非神经元细胞转化为神经元细胞的方法 |
CN110093309B (zh) * | 2018-01-29 | 2021-07-02 | 中国科学院动物研究所 | 一种诱导成纤维细胞转分化为脂肪细胞的方法 |
CN110093305B (zh) * | 2018-01-29 | 2021-07-02 | 中国科学院动物研究所 | 一种诱导肝细胞体外扩增的方法 |
CN110093310B (zh) * | 2018-01-29 | 2021-07-02 | 中国科学院动物研究所 | 一种将成纤维细胞转化为永生化细胞的方法及其应用 |
EP3747991A4 (en) * | 2018-01-29 | 2022-01-19 | Institute Of Zoology, Chinese Academy Of Sciences | METHOD OF INDUCING CELLS |
EP3746109A4 (en) * | 2018-02-02 | 2021-11-03 | The Penn State Research Foundation | METHODS AND MATERIALS FOR TREATING BRAIN INJURY |
CN110305846A (zh) * | 2018-03-20 | 2019-10-08 | 中山大学中山眼科中心 | 视网膜节细胞的制备方法 |
CN112384612A (zh) * | 2018-06-22 | 2021-02-19 | 皮肤2神经元私人有限公司 | 神经元前体细胞的扩增和分化 |
US11617745B2 (en) | 2018-08-17 | 2023-04-04 | Frequency Therapeutics, Inc. | Compositions and methods for generating hair cells by downregulating FOXO |
JP2021533788A (ja) | 2018-08-17 | 2021-12-09 | フリークエンシー セラピューティクス インコーポレイテッド | Jag−1を上方制御することにより有毛細胞を生成するための組成物及び方法 |
AU2019343166A1 (en) * | 2018-09-19 | 2021-05-20 | Regeneration Biomedical, Inc. | WNT-activated adipose-derived stem cell apparatuses, methods and systems |
US11518971B2 (en) | 2018-11-27 | 2022-12-06 | Research Triangle Institute | Method and apparatus for spatial control of cellular growth |
US20220186183A1 (en) * | 2019-01-02 | 2022-06-16 | Cellapeutics Bio | Novel glia-like cells differenatiated from somatic cells, preparation method therefor, cocktail composition for preparing same, cell therapeutic agent for preventing or treating neurological disorders, comprising same, and method for preventing and treating neurological disorders by administering same |
EP3908297A4 (en) * | 2019-01-11 | 2022-06-29 | Figene, LLC | Fibroblast regenerative cells |
KR102183208B1 (ko) * | 2019-07-25 | 2020-11-25 | 한국과학기술연구원 | Ngn2(neurogenin-2)를 이용하여 척수 손상 모델에서 반응성 성상세포를 신경세포로 리프로그래밍하는 방법 |
CA3164120A1 (en) * | 2019-12-09 | 2021-06-17 | The Brigham And Women's Hospital, Inc. | Methods for generating hematopoietic stem cells |
CN111471651A (zh) * | 2020-04-24 | 2020-07-31 | 中国人民解放军第四军医大学 | 一种人脂肪干细胞无血清培养基及其制备方法 |
CN113862218A (zh) * | 2021-10-12 | 2021-12-31 | 广州医科大学附属第一医院(广州呼吸中心) | 一种肿瘤相关性血管周细胞亚群及制备方法与应用 |
Family Cites Families (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6087168A (en) | 1999-01-20 | 2000-07-11 | Cedars Sinai Medical Center | Conversion of non-neuronal cells into neurons: transdifferentiation of epidermal cells |
US20020136709A1 (en) | 2000-12-12 | 2002-09-26 | Nucleus Remodeling, Inc. | In vitro-derived adult pluripotent stem cells and uses therefor |
AU2002313817A1 (en) * | 2001-08-27 | 2003-03-10 | Advanced Cell Technology, Inc. | Trans-differentiation and re-differentiation of somatic cells and production of cells for cell therapies |
US20030217378A1 (en) | 2002-04-05 | 2003-11-20 | The University Of Georgia Research Foundation, Inc | Cloning using rapidly matured oocytes |
AU2003252559A1 (en) * | 2002-08-17 | 2004-03-03 | Hae-Young Suh | A method for transdifferentiating mesenchymal stem cells into neuronal cells |
WO2006086746A2 (en) * | 2005-02-09 | 2006-08-17 | Burnham Institute For Medical Research | Homogeneous neural precursor cells |
WO2007016037A2 (en) | 2005-07-27 | 2007-02-08 | Board Of Regents, The University Of Texas System | Methods for trans-differentiating cells |
CN101389761A (zh) | 2006-02-27 | 2009-03-18 | 银怎株式会社 | 使用bmi-1使星形胶质细胞去分化成为神经干细胞 |
EP2099290A4 (en) * | 2006-12-07 | 2010-01-13 | Teva Pharma | PROCESS FOR GENERATING AND EXPANDING PROGENITOR CELLS OF TISSUES AND TISSUE CELLS MILLED FROM INTACT BONE MARROW OR UMBILICAL INTACT CORD TISSUE |
WO2009018832A1 (en) * | 2007-08-09 | 2009-02-12 | Rigshospitalet | Method for increasing the plasticity level of a cell |
ES2589122T3 (es) | 2007-08-31 | 2016-11-10 | Whitehead Institute For Biomedical Research | Estimulación de la ruta de la Wnt en la reprogramación de células somáticas |
EP2096169B1 (en) | 2007-10-31 | 2020-11-18 | Kyoto University | Nuclear reprogramming method |
US20090136461A1 (en) * | 2007-11-28 | 2009-05-28 | Moon Suk Kim | Neuronal differentiation method of adult stem cells using small molecules |
EP2245140A2 (en) * | 2007-11-30 | 2010-11-03 | New York Medical College | Compositions comprising hdac inhibitors and methods of their use in restoring stem cell function and preventing heart failure |
EP2242838A1 (en) | 2007-12-17 | 2010-10-27 | GliaMed, Inc. | Stem-like cells and method for reprogramming adult mammalian somatic cells |
SG10201607710UA (en) * | 2008-03-17 | 2016-11-29 | Scripps Research Inst | Combined chemical and genetic approaches for generation of induced pluripotent stem cells |
WO2009126655A2 (en) * | 2008-04-07 | 2009-10-15 | Nupotential, Inc. | Reprogramming a cell by inducing a pluripotent gene through use of a small molecule modulator |
WO2010052904A1 (en) | 2008-11-05 | 2010-05-14 | Keio University | Method for producing neural stem cells |
EP2393915A4 (en) | 2009-02-05 | 2012-12-26 | Regenertech Pty Ltd | PROCESS FOR THE PREPARATION OF PRECURSOR CELLS FROM DIFFERENTIATED CELLS |
US20120115225A1 (en) * | 2009-04-23 | 2012-05-10 | Xu C W | Reprogramming of somatic cells with purified proteins |
JP5921430B2 (ja) * | 2009-05-20 | 2016-05-24 | マヨ ファウンデーション フォー メディカル エデュケーション アンド リサーチMayo Foundation For Medical Education And Research | 哺乳類細胞の心臓発生能を決定する方法 |
US9453205B2 (en) * | 2009-10-31 | 2016-09-27 | Genesis Technologies Limited | Methods for reprogramming cells and uses thereof |
AU2010312240B2 (en) * | 2009-10-31 | 2016-12-15 | Genesis Technologies Limited | Methods for reprogramming cells and uses thereof |
WO2011163531A2 (en) * | 2010-06-23 | 2011-12-29 | Vivoscript, Inc. | Compositions and methods for re-programming cells without genetic modification for treatment of cardiovascular diseases |
WO2013033213A1 (en) * | 2011-08-30 | 2013-03-07 | The J. David Gladstone Institutes | Methods for generating cardiomyocytes |
WO2013116307A1 (en) | 2012-01-30 | 2013-08-08 | Mount Sinai School Of Medicine | Method for programming differentiated cells into hematopoietic stem cells |
-
2010
- 2010-11-01 AU AU2010312240A patent/AU2010312240B2/en active Active
- 2010-11-01 US US13/504,988 patent/US9528087B2/en active Active
- 2010-11-01 LT LTEP10825907.8T patent/LT2494039T/lt unknown
- 2010-11-01 EP EP10825907.8A patent/EP2494039B1/en active Active
- 2010-11-01 JP JP2012535565A patent/JP5982286B2/ja active Active
- 2010-11-01 KR KR1020187008318A patent/KR102014977B1/ko active IP Right Grant
- 2010-11-01 KR KR1020197024507A patent/KR102134240B1/ko active IP Right Grant
- 2010-11-01 DK DK10825907.8T patent/DK2494039T3/da active
- 2010-11-01 MX MX2012004881A patent/MX353245B/es active IP Right Grant
- 2010-11-01 EP EP19170686.0A patent/EP3567103B1/en active Active
- 2010-11-01 BR BR112012009921-3A patent/BR112012009921B1/pt not_active IP Right Cessation
- 2010-11-01 SI SI201031910T patent/SI2494039T1/sl unknown
- 2010-11-01 KR KR1020127014081A patent/KR101874463B1/ko active IP Right Grant
- 2010-11-01 SG SG10201702120VA patent/SG10201702120VA/en unknown
- 2010-11-01 CA CA2779310A patent/CA2779310C/en active Active
- 2010-11-01 WO PCT/CA2010/001727 patent/WO2011050476A1/en active Application Filing
- 2010-11-01 ES ES10825907T patent/ES2739672T3/es active Active
-
2012
- 2012-04-29 IL IL219453A patent/IL219453A/en active IP Right Grant
- 2012-05-29 ZA ZA2012/03902A patent/ZA201203902B/en unknown
-
2016
- 2016-03-24 JP JP2016059620A patent/JP2016146841A/ja active Pending
- 2016-10-19 US US15/298,006 patent/US10131879B2/en active Active
- 2016-10-19 US US15/297,972 patent/US10017737B2/en active Active
- 2016-10-19 US US15/298,034 patent/US10260046B2/en active Active
-
2017
- 2017-03-15 AU AU2017201774A patent/AU2017201774B2/en active Active
- 2017-08-24 IL IL254144A patent/IL254144A0/en unknown
-
2018
- 2018-07-04 JP JP2018127585A patent/JP2018183152A/ja active Pending
- 2018-11-19 US US16/195,005 patent/US10557123B2/en active Active
-
2019
- 2019-04-09 AU AU2019202451A patent/AU2019202451B2/en active Active
- 2019-07-03 HR HRP20191213TT patent/HRP20191213T1/hr unknown
-
2020
- 2020-01-24 US US16/752,462 patent/US20200165570A1/en not_active Abandoned
- 2020-02-23 IL IL272848A patent/IL272848B/en active IP Right Grant
- 2020-05-07 JP JP2020082207A patent/JP2020124219A/ja active Pending
-
2022
- 2022-06-16 JP JP2022097154A patent/JP7407865B2/ja active Active
-
2023
- 2023-03-22 US US18/188,421 patent/US20230227785A1/en active Pending
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2016146841A (ja) * | 2009-10-31 | 2016-08-18 | ニュー・ワールド・ラボラトリーズ・インコーポレイテッドNew World Laboratories Inc. | 細胞の再プログラミングのための方法とその用途 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7407865B2 (ja) | 細胞の再プログラミングのための方法とその用途 | |
US11795439B2 (en) | Methods for reprogramming cells and uses thereof | |
EP2982747B1 (en) | Method for producing reprogrammed derivative neuronal stem cell from non-neuronal cell by using hmga2 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20131028 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20150127 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20150424 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20150526 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20150625 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150724 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20150724 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20151124 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160324 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20160510 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20160712 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20160801 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5982286 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |