JP6329911B2 - 星状膠細胞作製のためのミクロrna - Google Patents
星状膠細胞作製のためのミクロrna Download PDFInfo
- Publication number
- JP6329911B2 JP6329911B2 JP2014558253A JP2014558253A JP6329911B2 JP 6329911 B2 JP6329911 B2 JP 6329911B2 JP 2014558253 A JP2014558253 A JP 2014558253A JP 2014558253 A JP2014558253 A JP 2014558253A JP 6329911 B2 JP6329911 B2 JP 6329911B2
- Authority
- JP
- Japan
- Prior art keywords
- mir
- cells
- mirna
- disease
- mscs
- 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.)
- Expired - Fee Related
Links
Classifications
-
- 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
- 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
- A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived 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
- A61K35/48—Reproductive organs
- A61K35/50—Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic 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
- A61K35/48—Reproductive organs
- A61K35/51—Umbilical cord; Umbilical cord blood; Umbilical stem cells
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- C12N5/0622—Glial cells, e.g. astrocytes, oligodendrocytes; Schwann cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering N.A.
- C12N2310/141—MicroRNAs, miRNAs
-
- 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
- C12N2320/00—Applications; Uses
- C12N2320/10—Applications; Uses in screening processes
- C12N2320/11—Applications; Uses in screening processes for the determination of target sites, i.e. of active nucleic acids
-
- 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
- C12N2330/00—Production
- C12N2330/10—Production naturally occurring
-
- 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
- C12N2501/01—Modulators of cAMP or cGMP, e.g. non-hydrolysable analogs, phosphodiesterase inhibitors, cholera toxin
-
- 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
- C12N2501/135—Platelet-derived growth factor [PDGF]
-
- 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
- C12N2501/195—Heregulin, neu differentiation 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
- C12N2501/40—Regulators of development
- C12N2501/41—Hedgehog proteins; Cyclopamine (inhibitor)
-
- 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
- C12N2501/65—MicroRNA
-
- 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
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/13—Coculture with; Conditioned medium produced by connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic 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
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/13—Coculture with; Conditioned medium produced by connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic fibroblasts"
- C12N2502/1305—Adipocytes
-
- 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
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/13—Coculture with; Conditioned medium produced by connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic fibroblasts"
- C12N2502/1311—Osteocytes, osteoblasts, odontoblasts
-
- 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
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/13—Coculture with; Conditioned medium produced by connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic fibroblasts"
- C12N2502/1317—Chondrocytes
-
- 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
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/13—Coculture with; Conditioned medium produced by connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic fibroblasts"
- C12N2502/1323—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
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/13—Coculture with; Conditioned medium produced by connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic fibroblasts"
- C12N2502/1329—Cardiomyocytes
-
- 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
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/13—Coculture with; Conditioned medium produced by connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic fibroblasts"
- C12N2502/1335—Skeletal muscle cells, myocytes, myoblasts, myotubes
-
- 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
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/13—Coculture with; Conditioned medium produced by connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic fibroblasts"
- C12N2502/1341—Tenocytes, cells from tendons and ligaments
-
- 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
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/13—Coculture with; Conditioned medium produced by connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic fibroblasts"
- C12N2502/1347—Smooth muscle 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
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/13—Coculture with; Conditioned medium produced by connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic fibroblasts"
- C12N2502/1352—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
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/13—Coculture with; Conditioned medium produced by connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic fibroblasts"
- C12N2502/1352—Mesenchymal stem cells
- C12N2502/1358—Bone marrow mesenchymal stem cells (BM-MSC)
-
- 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
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/13—Coculture with; Conditioned medium produced by connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic fibroblasts"
- C12N2502/1352—Mesenchymal stem cells
- C12N2502/1364—Dental pulp stem cells, dental follicle 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
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/13—Coculture with; Conditioned medium produced by connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic fibroblasts"
- C12N2502/1352—Mesenchymal stem cells
- C12N2502/137—Blood-borne mesenchymal stem cells, e.g. Msc from umbilical cord blood
-
- 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
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/13—Coculture with; Conditioned medium produced by connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic fibroblasts"
- C12N2502/1352—Mesenchymal stem cells
- C12N2502/1376—Mesenchymal stem cells from hair follicles
-
- 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
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/13—Coculture with; Conditioned medium produced by connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic fibroblasts"
- C12N2502/1352—Mesenchymal stem cells
- C12N2502/1382—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
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/13—Coculture with; Conditioned medium produced by connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic fibroblasts"
- C12N2502/1352—Mesenchymal stem cells
- C12N2502/1388—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
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/13—Coculture with; Conditioned medium produced by connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic fibroblasts"
- C12N2502/1394—Bone marrow stromal cells; whole marrow
-
- 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
- C12N2506/025—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from embryonic cells from extra-embryonic cells, e.g. trophoblast, placenta
-
- 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
- C12N2506/1353—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 bone marrow mesenchymal stem cells (BM-MSC)
-
- 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
- C12N2506/1369—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 blood-borne mesenchymal stem cells, e.g. MSC from umbilical blood
-
- 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
- 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
- C12N2506/1392—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 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
- C12N2510/00—Genetically modified cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/178—Oligonucleotides characterized by their use miRNA, siRNA or ncRNA
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Cell Biology (AREA)
- General Health & Medical Sciences (AREA)
- Developmental Biology & Embryology (AREA)
- Zoology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Biotechnology (AREA)
- Immunology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Virology (AREA)
- Epidemiology (AREA)
- Wood Science & Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Genetics & Genomics (AREA)
- Hematology (AREA)
- Reproductive Health (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Analytical Chemistry (AREA)
- Pregnancy & Childbirth (AREA)
- Biophysics (AREA)
- Ophthalmology & Optometry (AREA)
- Molecular Biology (AREA)
- Physics & Mathematics (AREA)
- Hospice & Palliative Care (AREA)
Description
(a)MSCの集団を星状膠細胞の表現型に向かって分化させること;および
(b)MSCの集団におけるmiRNAの発現における変化を、前記MSCを星状膠細胞の表現型に向かって分化させる前および分化させた後において分析すること(ただし、所定のレベルを越えるか、または下回るmiRNAの発現の変化により、前記miRNAが前記神経疾患または神経障害の処置のために調節され得ることが示される)
を含む方法が提供される。
1.間葉系幹細胞を成熟型miRNA(または本明細書中下記で記載されるように改変形態)により一過性にトランスフェクションすること。本発明の教示に従って設計されるmiRNAは、酵素的合成および固相合成の両方を含めて、当技術分野で公知の任意のオリゴヌクレオチド合成法に従って作製することができる。固相合成を実行するための様々な設備および試薬が、例えば、Applied Biosystemsから市販されている。そのような合成のための任意の他の手段もまた用いることができる;オリゴヌクレオチドの実際の合成は十分に当業者の能力の範囲内であり、固相化学(例えば、シアノエチルホスホルアミダイト)、その後、脱保護、脱塩および精製(例えば、自動トリチル・オン法またはHPLCによる精製)を利用して、例えば、下記において詳しく記載されるような確立された方法論により達成することができる:Sambrook,J.およびRussell,D.W.(2001)、“Molecular Cloning:A Laboratory Manual”;Ausubel,R.M.他編(1994、1989)、“Current Protocols in Molecular Biology”、第I巻〜第III巻、John Wiley&Sons、Baltimore、Maryland;Perbal,B.(1988)、“A Practical Guide to Molecular Cloning”、John Wiley&Sons、New York;およびGait,M.J.編(1984)、“Oligonucleotide Synthesis”。
2.間葉系幹細胞を、成熟型miRNAをコードする発現ベクターにより安定的または一過性にトランスフェクションすること。
3.間葉系幹細胞を、プレ−miRNAをコードする発現ベクターにより安定的または一過性にトランスフェクションすること。プレ−miRNA配列は、45〜90ヌクレオチド、60〜80ヌクレオチド、または60〜70ヌクレオチドを含む場合がある。プレ−miRNAの配列は、本明細書中に示されるようなmiRNAおよびmiRNA*を含む場合がある。プレ−miRNAの配列はまた、プリ−miRNAの5’末端および3’末端から0〜160個のヌクレオチドを除外するプリ−miRNAの配列である場合がある。プレ−miRNAの配列はmiRNAの配列を含む場合がある。
4.間葉系幹細胞を、プリ−miRNAをコードする発現ベクターにより安定的または一過性にトランスフェクションすること。プリ−miRNA配列は、45〜30000ヌクレオチド、50〜25000ヌクレオチド、100〜20000ヌクレオチド、1000〜1500ヌクレオチド、または80〜100ヌクレオチドを含む場合がある。プリ−miRNAの配列は、本明細書中に示されるようにプレ−miRNA、miRNAおよびmiRNA*、ならびに、それらの変化体を含む場合がある。miRNA模倣体の調製を化学的合成法によって、または、組換え法によって行うことができる。
miR−204,miR−224,miR−616,miR−122,miR−299,miR−100,miR−138,miR−140,miR−375,miR−217,miR−302,miR−372,miR−96,miR−127−3p,miR−449,miR−135b,miR−101,miR−326,miR−324,miR−335,miR−14,miR−16。
mir−410,mir−3163,mir−148a,mir−148b,mir−152,mir−3121−3p,mir−495,mir−203,mir−4680−3p。
1)分化MSC(様々な神経細胞または神経始原体細胞に至るもの)が、同種T細胞との一方向混合リンパ球培養において刺激因子として役立つ場合があり、同じドナーから単離される同種リンパ球に対して応答するT細胞との比較での増殖応答が、低応答性を実証するために3H−チミジン取り込みによって評価される場合がある。
2)分化MSCが、T細胞により媒介される増殖応答に対する免疫抑制影響を確認するために、一方向混合リンパ球培養に対して、また、T細胞マイトジェン(フィトヘマグルチニンおよびコンカナバリンA)との細胞培養に対して添加/共培養される場合がある。
3)Brown Norwayラットから培養される臍帯細胞および胎盤細胞(非改変細胞および分化細胞)がMSCについて富化される場合があり、これらの細胞が、誘導された実験的自己免疫性脳脊髄炎(EAE)を有するLewisラットに注入される場合がある。代替では、BALB/cマウスの(BALB/cxC57BL/6)F1から培養される臍帯細胞および胎盤細胞、または、Brown Norwayラットから得られる異種細胞(非改変細胞および分化細胞)がMSCについて富化される場合があり、これらの細胞が、誘導された実験的自己免疫性脳脊髄炎(EAE)を有するC57BL/6またはSJL/jレシピエントに注入される場合がある。麻痺に対する臨床効果が、異種のMHC、完全不一致MSCまたはハプロタイプ一致した不一致MSCの治療効果を評価するために調べられる場合がある。そのような実験は、遺伝的障害または遺伝的傾向のある障害を有する患者を家族の一員のハプロタイプ一致したMSCにより処置するための基礎を提供する場合がある。
4)臍帯および胎盤から培養されるBALB/cのMSCが、GFPまたはRFPにより標識されるプレ−miRとともに輸注される場合がある(この場合、GFPまたはRFPは、本発明者らが、誘導されたEAEを有するC57BL/6レシピエントの脳におけるこれらの細胞の遊走および持続を追跡することを可能にするであろう)。標識されたMHC不一致の分化MSCの臨床効果が、疾患、麻痺および組織病理学の兆候をモニターすることによって評価される場合がある。そのような細胞の遊走および局在化もまた、遺伝的に形質導入されたGFP「緑色」ドナーまたはRed2「赤色」ドナーに由来する蛍光性細胞を使用することによってモニターされる場合がある。
MSCを星状膠細胞表現型に向かって分化させるための可溶性因子
材料および方法
星状膠細胞表現型を発現する細胞へのMSCの分化:4つの異なる供給源から得られるMSC(骨髄(BM−MSC)、脂肪細胞由来(AD−MSC)、臍帯由来細胞および胎盤由来細胞)をこれらの研究において用いた。細胞を最初、DMEM+10%FCSに1日間置床し、その後、SHH(250ng/ml)、FGFb(50ng/ml)およびEGF(50ng/ml)を含有するNM培地に5日間にわたって移した。細胞を、IBMX(0.5mM)、dbcycAMP(1mM)、PDGF(5ng/ml)、ニューレグリン(50ng/ml)およびFGFb(20ng/ml)とさらに10日間インキュベーションした。最後の段階で、細胞を、同じ因子が補充されるG5培地において5日間インキュベーションした。
ネスチン、Olig2、β−IIIチューブリン、GFAP、グルタミンシンターゼ。
上記の分化プロトコルを使用した場合、BM−MSC(図1)およびそれ以外のMSCタイプ(データは示されず)の両方が星状膠細胞性の形態学を示し、星状膠細胞のマーカーであるGFAPについて陽性で染色された(図1)。
MSCを星状膠細胞に分化させるためのmiRNA
材料および方法
miRNAマイクロアレイ分析:対照MSCおよび分化MSCにおける特異的miRNAの示差的発現を分析するために、幹細胞ミクロRNAのqPCRアレイを、SBI社から得られるquantiMiR(カタログ#RA620A−1)とともに用いた。
MSCの星状膠細胞への分化に関与している可能性のあるmiRNAを特定するために、対照の非改変MSCのmiRNAシグナチャーを星状膠細胞に分化させられるMSCに対して比較した。
MSCを星状膠細胞表現型に分化させるためのさらなるmiRNAの特定
材料および方法
骨髄の間葉系幹細胞(BM−MSC)をGFAP−GFPレポーターにより形質導入した。その後、細胞をantagomiR−138およびmiR−101の両方によりトランスフェクションした。細胞を10日後に蛍光顕微鏡で観察した。さらなる遺伝子アレイおよびmiRアレイを使用して、分化細胞を特徴づけた。
図9A〜図9Bに例示されるように、miR−138のサイレンシングをmiR−101の過剰発現と一緒に行うことにより、GFAP陽性細胞へのMSCの分化が引き起こされる。加えて、これらの細胞はまた、高レベルのグルタミン酸輸送体を発現した(データは示されず)。
miRNAを使用するMSCにおけるαシヌクレインのダウンレギュレーション
α−シヌクレインが成体の脳において広範囲に発現される。α−シヌクレイン遺伝子内の変異は常染色体優性家族性PDに伴う。ヒト野生型形態の過剰発現およびα−シヌクレイン変異型形態の発現は、不溶性凝集物を形成し、酸化ストレスに対するニューロンの増大した感受性を生じさせるレビー小体の主要構造を構成するより大きい傾向を示す。
配列
Claims (19)
- 神経疾患または神経障害を対象において処置するために有用である星状膠細胞の集団をエクスビボで作製する方法であって、外因性miR−101をMSCの集団において発現させ、かつ、miR−138のMSCの前記集団における発現をダウンレギュレーションし、それにより、前記星状膠細胞の集団を作製することを含む方法。
- 前記MSCが、骨髄、脂肪組織、胎盤、臍帯血および臍帯からなる群から選択される組織から単離される、請求項1に記載の方法。
- 前記MSCは前記対象に対して自己である、請求項1に記載の方法。
- 前記MSCは前記対象に対して非自己である、請求項1に記載の方法。
- 前記MSCは前記対象に対して半同種である、請求項1に記載の方法。
- 前記発現することが、前記MSCを、前記miR−101をコードするかまたは前記miR−101のプレ−miRNAをコードするポリヌクレオチド配列を含む発現ベクターによりトランスフェクションすることによって実行される、請求項1に記載の方法。
- 前記ダウンレギュレーションすることが、前記MSCを、前記miR−138にハイブリダイゼーションし、かつ、その機能を阻害するポリヌクレオチド配列を含む発現ベクターによりトランスフェクションすることによって実行される、請求項1に記載の方法。
- 前記miR−138にハイブリダイゼーションし、かつ、その機能を阻害するポリヌクレオチド配列が、miR−138に対するantagomiRである、請求項7に記載の方法。
- GFAP、EAAT1およびEAAT2からなる群から選択される少なくとも1つのマーカーの増大した発現を前記作製することの後において確認することをさらに含む、請求項1に記載の方法。
- 前記発現の後、前、または前記接触と同時に、血小板由来増殖因子(PDGF)、ニューレグリン、FGF−bおよびc−AMP誘導剤からなる群から選択される少なくとも1つの作用因子を含む分化培地において前記MSCをインキュベーションすることをさらに含む、請求項1に記載の方法。
- 外因性miR−101を含み、およびmiR−138にハイブリダイゼーションし、かつ、その機能を阻害するポリヌクレオチド作用因子を含む、間葉系幹細胞の遺伝子改変され単離された集団であって、前記細胞が星状膠細胞の表現型を有する、遺伝子改変され単離された細胞集団。
- 前記細胞集団の細胞の少なくとも50%が、GFAP、EAAT1およびEAAT2からなる群から選択される少なくとも1つのマーカーを発現する、請求項11に記載の単離された細胞集団。
- 脳疾患または脳障害を処置するための医薬の製造における、請求項11に記載の単離された細胞集団の使用。
- 前記脳疾患または脳障害が神経変性障害である、請求項13に記載の使用。
- 前記神経変性障害は、多発性硬化症、パーキンソン病、てんかん、筋萎縮性側索硬化症(ALS)、レット症候群、自己免疫性脳脊髄炎、卒中、アルツハイマー病、骨髄および脳の傷害、およびハンチントン病からなる群から選択される、請求項14に記載の使用。
- 請求項11または12に記載される単離された細胞集団と、医薬的に許容される担体とを含む医薬組成物。
- 神経疾患または神経障害の処置において使用するためのものである、請求項16に記載の医薬組成物。
- 前記神経疾患または神経障害は神経変性障害である、請求項17に記載の医薬組成物。
- 前記神経変性障害は、多発性硬化症、パーキンソン病、てんかん、筋萎縮性側索硬化症(ALS)、レット症候群、自己免疫性脳脊髄炎、卒中、アルツハイマー病、骨髄および脳の傷害、およびハンチントン病からなる群から選択される、請求項18に記載の医薬組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201261601624P | 2012-02-22 | 2012-02-22 | |
US61/601,624 | 2012-02-22 | ||
PCT/IB2013/051430 WO2013124817A2 (en) | 2012-02-22 | 2013-02-21 | MicroRNAS FOR THE GENERATION OF ASTROCYTES |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2015514392A JP2015514392A (ja) | 2015-05-21 |
JP6329911B2 true JP6329911B2 (ja) | 2018-05-23 |
Family
ID=48040382
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014558253A Expired - Fee Related JP6329911B2 (ja) | 2012-02-22 | 2013-02-21 | 星状膠細胞作製のためのミクロrna |
Country Status (4)
Country | Link |
---|---|
US (1) | US10034902B2 (ja) |
EP (2) | EP3401393B1 (ja) |
JP (1) | JP6329911B2 (ja) |
WO (1) | WO2013124817A2 (ja) |
Families Citing this family (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2808372C (en) | 2010-08-16 | 2021-11-16 | Brainstem Biotec Ltd. | Methods of generating oligodendrocytes and cell populations comprising same |
US10385314B2 (en) | 2010-08-16 | 2019-08-20 | Exostem Biotec Ltd. | Methods of generating oligodendrocytes and cell populations comprising same |
US10227593B2 (en) | 2011-12-13 | 2019-03-12 | Henry Ford Health System | Methods, systems, and compositions for cell-derived/vesicle-based microRNA delivery |
US10034902B2 (en) | 2012-02-22 | 2018-07-31 | Exostem Biotec Ltd. | MicroRNAs for the generation of astrocytes |
EP2844745A2 (en) | 2012-02-22 | 2015-03-11 | Brainstem Biotec Ltd. | Generation of neural stem cells and motor neurons |
WO2014113822A1 (en) * | 2013-01-18 | 2014-07-24 | Henry Ford Health System | Methods, systems, and compositions relating to mirna-146a |
US10308959B2 (en) | 2013-01-18 | 2019-06-04 | Henry Ford Health System | Methods, systems, and compositions relating to MiRNA-146a |
EP3223830A4 (en) * | 2014-11-24 | 2018-06-06 | Cytostormrx LLC | Encapsulated stem cells for the treatment of inflammatory disease |
KR101814868B1 (ko) * | 2015-06-18 | 2018-01-04 | 재단법인대구경북과학기술원 | 마이크로 rna와 nmda 수용체의 상관관계를 이용한 해마의 기능감소 판단 방법, 기능감소 억제 방법 및 기능감소 억제제 스크리닝 방법 |
JP7014449B2 (ja) * | 2016-08-14 | 2022-02-01 | ラモット アット テル アビブ ユニバーシティ, リミテッド | 神経障害を処置するための間葉系細胞由来エキソソーム |
IT201600093825A1 (it) * | 2016-09-19 | 2018-03-19 | Fondazione St Italiano Tecnologia | Composizione farmaceutica di miRNA e suoi usi terapeutici. |
CN106474549B (zh) * | 2016-11-21 | 2019-05-03 | 南通大学 | MicroRNA基因介导的新型组织工程化神经的构建及其在修复神经缺损的应用 |
US20200188440A1 (en) * | 2017-05-16 | 2020-06-18 | Exostem Biotec Ltd. | Methods of inhibiting aging and treating aging-related disorders |
WO2020212996A1 (en) * | 2019-04-18 | 2020-10-22 | Exostem Biotec Ltd. | Differentiated and nondifferentiated msc compositions and use thereof |
KR102285380B1 (ko) * | 2019-12-26 | 2021-08-02 | 한양대학교 산학협력단 | 마이크로RNA-24-3p의 억제제를 포함하는 신경아세포에서 신경세포로의 분화 유도용 조성물 및 방법 |
CN116333994A (zh) * | 2021-12-07 | 2023-06-27 | 上海鲸奇生物科技有限公司 | 非编码rna介导的神经性疾病治疗 |
Family Cites Families (99)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NL154600B (nl) | 1971-02-10 | 1977-09-15 | Organon Nv | Werkwijze voor het aantonen en bepalen van specifiek bindende eiwitten en hun corresponderende bindbare stoffen. |
US3687808A (en) | 1969-08-14 | 1972-08-29 | Univ Leland Stanford Junior | Synthetic polynucleotides |
NL154598B (nl) | 1970-11-10 | 1977-09-15 | Organon Nv | Werkwijze voor het aantonen en bepalen van laagmoleculire verbindingen en van eiwitten die deze verbindingen specifiek kunnen binden, alsmede testverpakking. |
NL154599B (nl) | 1970-12-28 | 1977-09-15 | Organon Nv | Werkwijze voor het aantonen en bepalen van specifiek bindende eiwitten en hun corresponderende bindbare stoffen, alsmede testverpakking. |
US3901654A (en) | 1971-06-21 | 1975-08-26 | Biological Developments | Receptor assays of biologically active compounds employing biologically specific receptors |
US3853987A (en) | 1971-09-01 | 1974-12-10 | W Dreyer | Immunological reagent and radioimmuno assay |
US3867517A (en) | 1971-12-21 | 1975-02-18 | Abbott Lab | Direct radioimmunoassay for antigens and their antibodies |
NL171930C (nl) | 1972-05-11 | 1983-06-01 | Akzo Nv | Werkwijze voor het aantonen en bepalen van haptenen, alsmede testverpakkingen. |
US3850578A (en) | 1973-03-12 | 1974-11-26 | H Mcconnell | Process for assaying for biologically active molecules |
US3935074A (en) | 1973-12-17 | 1976-01-27 | Syva Company | Antibody steric hindrance immunoassay with two antibodies |
US3996345A (en) | 1974-08-12 | 1976-12-07 | Syva Company | Fluorescence quenching with immunological pairs in immunoassays |
US4034074A (en) | 1974-09-19 | 1977-07-05 | The Board Of Trustees Of Leland Stanford Junior University | Universal reagent 2-site immunoradiometric assay using labelled anti (IgG) |
US3984533A (en) | 1975-11-13 | 1976-10-05 | General Electric Company | Electrophoretic method of detecting antigen-antibody reaction |
US4098876A (en) | 1976-10-26 | 1978-07-04 | Corning Glass Works | Reverse sandwich immunoassay |
US4879219A (en) | 1980-09-19 | 1989-11-07 | General Hospital Corporation | Immunoassay utilizing monoclonal high affinity IgM antibodies |
US4469863A (en) | 1980-11-12 | 1984-09-04 | Ts O Paul O P | Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof |
US5023243A (en) | 1981-10-23 | 1991-06-11 | Molecular Biosystems, Inc. | Oligonucleotide therapeutic agent and method of making same |
US4476301A (en) | 1982-04-29 | 1984-10-09 | Centre National De La Recherche Scientifique | Oligonucleotides, a process for preparing the same and their application as mediators of the action of interferon |
US5011771A (en) | 1984-04-12 | 1991-04-30 | The General Hospital Corporation | Multiepitopic immunometric assay |
US5550111A (en) | 1984-07-11 | 1996-08-27 | Temple University-Of The Commonwealth System Of Higher Education | Dual action 2',5'-oligoadenylate antiviral derivatives and uses thereof |
US4666828A (en) | 1984-08-15 | 1987-05-19 | The General Hospital Corporation | Test for Huntington's disease |
US5166315A (en) | 1989-12-20 | 1992-11-24 | Anti-Gene Development Group | Sequence-specific binding polymers for duplex nucleic acids |
US5235033A (en) | 1985-03-15 | 1993-08-10 | Anti-Gene Development Group | Alpha-morpholino ribonucleoside derivatives and polymers thereof |
US5034506A (en) | 1985-03-15 | 1991-07-23 | Anti-Gene Development Group | Uncharged morpholino-based polymers having achiral intersubunit linkages |
US5405938A (en) | 1989-12-20 | 1995-04-11 | Anti-Gene Development Group | Sequence-specific binding polymers for duplex nucleic acids |
US5185444A (en) | 1985-03-15 | 1993-02-09 | Anti-Gene Deveopment Group | Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages |
US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
US4801531A (en) | 1985-04-17 | 1989-01-31 | Biotechnology Research Partners, Ltd. | Apo AI/CIII genomic polymorphisms predictive of atherosclerosis |
US5264423A (en) | 1987-03-25 | 1993-11-23 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibitors for replication of retroviruses and for the expression of oncogene products |
US5276019A (en) | 1987-03-25 | 1994-01-04 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibitors for replication of retroviruses and for the expression of oncogene products |
US5188897A (en) | 1987-10-22 | 1993-02-23 | Temple University Of The Commonwealth System Of Higher Education | Encapsulated 2',5'-phosphorothioate oligoadenylates |
US4924624A (en) | 1987-10-22 | 1990-05-15 | Temple University-Of The Commonwealth System Of Higher Education | 2,',5'-phosphorothioate oligoadenylates and plant antiviral uses thereof |
EP0406309A4 (en) | 1988-03-25 | 1992-08-19 | The University Of Virginia Alumni Patents Foundation | Oligonucleotide n-alkylphosphoramidates |
US5278302A (en) | 1988-05-26 | 1994-01-11 | University Patents, Inc. | Polynucleotide phosphorodithioates |
US5216141A (en) | 1988-06-06 | 1993-06-01 | Benner Steven A | Oligonucleotide analogs containing sulfur linkages |
US5272057A (en) | 1988-10-14 | 1993-12-21 | Georgetown University | Method of detecting a predisposition to cancer by the use of restriction fragment length polymorphism of the gene for human poly (ADP-ribose) polymerase |
US5464764A (en) | 1989-08-22 | 1995-11-07 | University Of Utah Research Foundation | Positive-negative selection methods and vectors |
US5192659A (en) | 1989-08-25 | 1993-03-09 | Genetype Ag | Intron sequence analysis method for detection of adjacent and remote locus alleles as haplotypes |
US5399676A (en) | 1989-10-23 | 1995-03-21 | Gilead Sciences | Oligonucleotides with inverted polarity |
US5264564A (en) | 1989-10-24 | 1993-11-23 | Gilead Sciences | Oligonucleotide analogs with novel linkages |
US5264562A (en) | 1989-10-24 | 1993-11-23 | Gilead Sciences, Inc. | Oligonucleotide analogs with novel linkages |
US5177198A (en) | 1989-11-30 | 1993-01-05 | University Of N.C. At Chapel Hill | Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates |
US5587361A (en) | 1991-10-15 | 1996-12-24 | Isis Pharmaceuticals, Inc. | Oligonucleotides having phosphorothioate linkages of high chiral purity |
US5321131A (en) | 1990-03-08 | 1994-06-14 | Hybridon, Inc. | Site-specific functionalization of oligodeoxynucleotides for non-radioactive labelling |
US5470967A (en) | 1990-04-10 | 1995-11-28 | The Dupont Merck Pharmaceutical Company | Oligonucleotide analogs with sulfamate linkages |
US5677437A (en) | 1990-07-27 | 1997-10-14 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
US5541307A (en) | 1990-07-27 | 1996-07-30 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogs and solid phase synthesis thereof |
US5602240A (en) | 1990-07-27 | 1997-02-11 | Ciba Geigy Ag. | Backbone modified oligonucleotide analogs |
US5489677A (en) | 1990-07-27 | 1996-02-06 | Isis Pharmaceuticals, Inc. | Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms |
US5623070A (en) | 1990-07-27 | 1997-04-22 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
US5608046A (en) | 1990-07-27 | 1997-03-04 | Isis Pharmaceuticals, Inc. | Conjugated 4'-desmethyl nucleoside analog compounds |
US5618704A (en) | 1990-07-27 | 1997-04-08 | Isis Pharmacueticals, Inc. | Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling |
US5610289A (en) | 1990-07-27 | 1997-03-11 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogues |
DE69115702T2 (de) | 1990-08-03 | 1996-06-13 | Sterling Winthrop Inc | Verbindungen und verfahren zur unterdrückung der genexpression |
US5177196A (en) | 1990-08-16 | 1993-01-05 | Microprobe Corporation | Oligo (α-arabinofuranosyl nucleotides) and α-arabinofuranosyl precursors thereof |
US5214134A (en) | 1990-09-12 | 1993-05-25 | Sterling Winthrop Inc. | Process of linking nucleosides with a siloxane bridge |
US5561225A (en) | 1990-09-19 | 1996-10-01 | Southern Research Institute | Polynucleotide analogs containing sulfonate and sulfonamide internucleoside linkages |
JPH06505704A (ja) | 1990-09-20 | 1994-06-30 | ギリアド サイエンシズ,インコーポレイテッド | 改変ヌクレオシド間結合 |
US5486359A (en) | 1990-11-16 | 1996-01-23 | Osiris Therapeutics, Inc. | Human mesenchymal stem cells |
US5714331A (en) | 1991-05-24 | 1998-02-03 | Buchardt, Deceased; Ole | Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility |
US5539082A (en) | 1993-04-26 | 1996-07-23 | Nielsen; Peter E. | Peptide nucleic acids |
US5719262A (en) | 1993-11-22 | 1998-02-17 | Buchardt, Deceased; Ole | Peptide nucleic acids having amino acid side chains |
US5571799A (en) | 1991-08-12 | 1996-11-05 | Basco, Ltd. | (2'-5') oligoadenylate analogues useful as inhibitors of host-v5.-graft response |
US5633360A (en) | 1992-04-14 | 1997-05-27 | Gilead Sciences, Inc. | Oligonucleotide analogs capable of passive cell membrane permeation |
US5434257A (en) | 1992-06-01 | 1995-07-18 | Gilead Sciences, Inc. | Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages |
US5281521A (en) | 1992-07-20 | 1994-01-25 | The Trustees Of The University Of Pennsylvania | Modified avidin-biotin technique |
US5476925A (en) | 1993-02-01 | 1995-12-19 | Northwestern University | Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups |
GB9304618D0 (en) | 1993-03-06 | 1993-04-21 | Ciba Geigy Ag | Chemical compounds |
WO1994022891A1 (en) | 1993-03-31 | 1994-10-13 | Sterling Winthrop Inc. | Oligonucleotides with amide linkages replacing phosphodiester linkages |
US5625050A (en) | 1994-03-31 | 1997-04-29 | Amgen Inc. | Modified oligonucleotides and intermediates useful in nucleic acid therapeutics |
US5541110A (en) | 1994-05-17 | 1996-07-30 | Bristol-Myers Squibb | Cloning and expression of a gene encoding bryodin 1 from Bryonia dioica |
ES2246085T3 (es) | 1998-05-07 | 2006-02-01 | University Of South Florida | Celulas de medula osea como fuente de neuronas util para reparar la medula espinal y el cerebro. |
US6303374B1 (en) | 2000-01-18 | 2001-10-16 | Isis Pharmaceuticals Inc. | Antisense modulation of caspase 3 expression |
KR100449141B1 (ko) * | 2001-04-19 | 2004-09-21 | (주)라이프코드 | 간엽 간세포를 신경세포로 분화시키는 방법 |
US20050058641A1 (en) | 2002-05-22 | 2005-03-17 | Siemionow Maria Z. | Tolerance induction and maintenance in hematopoietic stem cell allografts |
SE0301087D0 (sv) * | 2003-04-14 | 2003-04-14 | Cartela Ab | New monoclonal antibody |
EP1506997A1 (en) | 2003-08-14 | 2005-02-16 | NeuroProgen GmbH Leipzig | Method of generating neural stem cells |
CA2565070A1 (en) | 2004-04-28 | 2005-11-24 | Fibrogen, Inc. | Anti-ctgf agents for the treatment of pancreatic cancer |
CA2850323A1 (en) | 2004-11-12 | 2006-12-28 | Asuragen, Inc. | Methods and compositions involving mirna and mirna inhibitor molecules |
EP1705245B1 (en) | 2005-03-23 | 2009-05-20 | Stiftung CAESAR | Neural stem cells |
ES2524996T3 (es) * | 2005-06-16 | 2014-12-16 | Ramot At Tel Aviv University Ltd. | Células aisladas y poblaciones que comprenden a las mismas para el tratamiento de enfermedades del SNC |
KR101022401B1 (ko) | 2005-09-29 | 2011-03-15 | 아주대학교산학협력단 | 자살유전자를 발현하는 중간엽 줄기세포를 포함하는 암치료용 조성물 |
WO2007066338A1 (en) | 2005-12-08 | 2007-06-14 | Ramot At Tel Aviv University Ltd. | Isolated oligodendrocyte-like cells and populations comprising same for the treatment of cns diseases |
WO2008026198A2 (en) | 2006-08-28 | 2008-03-06 | Yeda Research And Development Co. Ltd. | Methods of generating glial and neuronal cells and use of same for the treatment of medical conditions of the cns |
US20080176328A1 (en) | 2007-01-19 | 2008-07-24 | Seoul National University Industry Foundation | Method of inducing differentiation of mesenchymal stem cells into neurons |
WO2009023525A2 (en) | 2007-08-09 | 2009-02-19 | Dharmacon, Inc. | Methods of modulating mesenchymal stem cell differentiation |
EP2268797A1 (en) | 2008-03-31 | 2011-01-05 | Hadasit Medical Research Services & Development Limited | Motor neurons developed from stem cells |
US8663987B2 (en) | 2008-05-28 | 2014-03-04 | Ramot At Tel-Aviv University Ltd. | Mesenchymal stem cells for the treatment of CNS diseases |
AU2010229872A1 (en) | 2009-03-26 | 2011-11-03 | The Regents Of The University Of California | Mesenchymal stem cells producing inhibitory RNA for disease modification |
US10421961B2 (en) * | 2009-06-10 | 2019-09-24 | Exostem Biotec Ltd | Methods, systems, and compositions for neuronal differentiation of multipotent stromal cells |
EP2475784A1 (en) | 2009-09-08 | 2012-07-18 | Ramot at Tel-Aviv University Ltd. | Methods of diagnosing amyotrophic lateral sclerosis (als) |
WO2011103016A2 (en) * | 2010-02-19 | 2011-08-25 | The Regents Of The University Of Michigan | Compositions and methods for inhibiting ezh2 |
WO2011159075A2 (ko) | 2010-06-14 | 2011-12-22 | 차의과학대학교 산학협력단 | 2차원 배양을 이용한 성체줄기세포의 신경전구세포로의 분화방법 및 신경전구세포를 이용한 신경손상 질환 치료용 약학 조성물 |
KR101183620B1 (ko) | 2010-06-18 | 2012-09-18 | 서울대학교산학협력단 | 지방조직 유래의 간엽줄기세포를 포함하는 파킨슨병 진단용 조성물 및 파킨슨병 진단용 바이오마커 |
CN103189511B (zh) * | 2010-07-12 | 2016-10-12 | 国立大学法人鸟取大学 | 利用siRNA导入的新型hiPSC制作法 |
CA2808372C (en) | 2010-08-16 | 2021-11-16 | Brainstem Biotec Ltd. | Methods of generating oligodendrocytes and cell populations comprising same |
EP2844745A2 (en) | 2012-02-22 | 2015-03-11 | Brainstem Biotec Ltd. | Generation of neural stem cells and motor neurons |
US10034902B2 (en) | 2012-02-22 | 2018-07-31 | Exostem Biotec Ltd. | MicroRNAs for the generation of astrocytes |
US20150024966A1 (en) | 2012-02-22 | 2015-01-22 | Brainstem Biotec Ltd. | Mesenchymal stem cells for in vitro modeling and cell-based therapy of human diseases and banks thereof |
-
2013
- 2013-02-21 US US14/380,155 patent/US10034902B2/en active Active
- 2013-02-21 EP EP18180526.8A patent/EP3401393B1/en active Active
- 2013-02-21 JP JP2014558253A patent/JP6329911B2/ja not_active Expired - Fee Related
- 2013-02-21 EP EP13713247.8A patent/EP2844744A2/en not_active Withdrawn
- 2013-02-21 WO PCT/IB2013/051430 patent/WO2013124817A2/en active Application Filing
Also Published As
Publication number | Publication date |
---|---|
JP2015514392A (ja) | 2015-05-21 |
EP3401393A1 (en) | 2018-11-14 |
US10034902B2 (en) | 2018-07-31 |
US20150037298A1 (en) | 2015-02-05 |
EP3401393B1 (en) | 2020-02-19 |
WO2013124817A3 (en) | 2014-01-03 |
WO2013124817A8 (en) | 2013-10-31 |
WO2013124817A2 (en) | 2013-08-29 |
EP2844744A2 (en) | 2015-03-11 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20200377854A1 (en) | Generation of neural stem cells and motor neurons | |
JP6329911B2 (ja) | 星状膠細胞作製のためのミクロrna | |
US20210228647A1 (en) | Mesenchymal stem cell and use thereof for treatment of muscle injury and muscle-associated diseases | |
JP2024073546A (ja) | 幹細胞微粒子 | |
CA2808372C (en) | Methods of generating oligodendrocytes and cell populations comprising same | |
US11667916B2 (en) | Composition for preventing or treating liver fibrosis, containing exosome or exosome-derived ribonucleic acid | |
EP3624817A1 (en) | Methods of inhibiting aging and treating aging-related disorders | |
US20150024966A1 (en) | Mesenchymal stem cells for in vitro modeling and cell-based therapy of human diseases and banks thereof | |
US20190015453A1 (en) | MicroRNAS FOR THE GENERATION OF ASTROCYTES | |
TW202140783A (zh) | 活體外誘導多潛能性幹細胞增殖及分化 | |
US11624067B2 (en) | In-vitro induction of adult stem cell expansion and derivation | |
US20190367873A1 (en) | Methods of generating oligodendrocytes and cell populations comprising same | |
KR20140046339A (ko) | miRNA-203의 억제를 이용한 줄기세포의 망막세포로의 분화방법 | |
EP3587575A1 (en) | Mirna mir-218 and use thereof for stimulating mesenchymal stem cells | |
WO2024151776A2 (en) | Compositions and methods for treating a neurologic disease using dopaminergic neurons with enhanced anti-inflammatory activity | |
Chang et al. | MicroRNAs in Development, Stem Cell Differentiation, and Regenerative Medicine | |
Linda | Molecular Characterization of Human Adipose Tissue-derived Stem Cells |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20160219 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20161025 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20170123 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170418 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20171006 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20171227 |
|
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: 20180330 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20180423 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6329911 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
LAPS | Cancellation because of no payment of annual fees |