JP2013226159A - 神経前駆細胞又は神経幹細胞の神経細胞への分化及び増殖の誘導方法、分化及び増殖誘導用組成物、及び薬学的製剤 - Google Patents
神経前駆細胞又は神経幹細胞の神経細胞への分化及び増殖の誘導方法、分化及び増殖誘導用組成物、及び薬学的製剤 Download PDFInfo
- Publication number
- JP2013226159A JP2013226159A JP2013160426A JP2013160426A JP2013226159A JP 2013226159 A JP2013226159 A JP 2013226159A JP 2013160426 A JP2013160426 A JP 2013160426A JP 2013160426 A JP2013160426 A JP 2013160426A JP 2013226159 A JP2013226159 A JP 2013226159A
- Authority
- JP
- Japan
- Prior art keywords
- neural
- cells
- stem cells
- disease
- mesenchymal stem
- 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.)
- Granted
Links
- 210000001178 neural stem cell Anatomy 0.000 title claims abstract description 42
- 230000004069 differentiation Effects 0.000 title claims abstract description 27
- 230000035755 proliferation Effects 0.000 title claims abstract description 21
- 238000000034 method Methods 0.000 title claims abstract description 18
- 239000000203 mixture Substances 0.000 title claims abstract description 17
- 230000001939 inductive effect Effects 0.000 title claims abstract description 15
- 210000003061 neural cell Anatomy 0.000 title claims abstract description 13
- 210000004027 cell Anatomy 0.000 title abstract description 46
- 230000001537 neural effect Effects 0.000 title abstract description 7
- 239000002243 precursor Substances 0.000 title abstract description 4
- 239000008194 pharmaceutical composition Substances 0.000 title description 4
- 210000002901 mesenchymal stem cell Anatomy 0.000 claims abstract description 63
- 210000004700 fetal blood Anatomy 0.000 claims abstract description 56
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 28
- 208000028389 Nerve injury Diseases 0.000 claims abstract description 10
- 230000008764 nerve damage Effects 0.000 claims abstract description 10
- 208000020431 spinal cord injury Diseases 0.000 claims abstract description 8
- 208000015114 central nervous system disease Diseases 0.000 claims abstract description 7
- 230000000472 traumatic effect Effects 0.000 claims abstract description 7
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 6
- 201000011240 Frontotemporal dementia Diseases 0.000 claims abstract description 6
- 208000023105 Huntington disease Diseases 0.000 claims abstract description 6
- 208000018737 Parkinson disease Diseases 0.000 claims abstract description 6
- 208000000609 Pick Disease of the Brain Diseases 0.000 claims abstract description 6
- 208000006011 Stroke Diseases 0.000 claims abstract description 6
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims abstract description 6
- 210000005155 neural progenitor cell Anatomy 0.000 claims description 23
- 210000002569 neuron Anatomy 0.000 claims description 20
- 238000012258 culturing Methods 0.000 claims description 14
- 230000005779 cell damage Effects 0.000 claims description 5
- 208000037887 cell injury Diseases 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
- 238000002659 cell therapy Methods 0.000 abstract description 5
- 238000002955 isolation Methods 0.000 abstract 1
- 230000002062 proliferating effect Effects 0.000 abstract 1
- 239000002609 medium Substances 0.000 description 9
- 238000012744 immunostaining Methods 0.000 description 7
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 6
- 101000713575 Homo sapiens Tubulin beta-3 chain Proteins 0.000 description 6
- 102100036790 Tubulin beta-3 chain Human genes 0.000 description 6
- 210000004556 brain Anatomy 0.000 description 6
- 230000006378 damage Effects 0.000 description 6
- 210000005087 mononuclear cell Anatomy 0.000 description 6
- 210000000130 stem cell Anatomy 0.000 description 6
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- 102000009664 Microtubule-Associated Proteins Human genes 0.000 description 5
- 108010020004 Microtubule-Associated Proteins Proteins 0.000 description 5
- 208000027418 Wounds and injury Diseases 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 238000003501 co-culture Methods 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 239000012091 fetal bovine serum Substances 0.000 description 5
- 208000014674 injury Diseases 0.000 description 5
- 239000001963 growth medium Substances 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 210000003606 umbilical vein Anatomy 0.000 description 4
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 3
- 210000001185 bone marrow Anatomy 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 210000005036 nerve Anatomy 0.000 description 3
- 210000004498 neuroglial cell Anatomy 0.000 description 3
- 238000009256 replacement therapy Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 241000283707 Capra Species 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 239000012981 Hank's balanced salt solution Substances 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 210000001130 astrocyte Anatomy 0.000 description 2
- 239000007640 basal medium Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 210000004748 cultured cell Anatomy 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 230000007472 neurodevelopment Effects 0.000 description 2
- 230000004031 neuronal differentiation Effects 0.000 description 2
- 210000004248 oligodendroglia Anatomy 0.000 description 2
- 210000001428 peripheral nervous system Anatomy 0.000 description 2
- 210000004116 schwann cell Anatomy 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000002356 single layer Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 1
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 229960003896 aminopterin Drugs 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000004271 bone marrow stromal cell Anatomy 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- -1 for example Substances 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 210000003041 ligament Anatomy 0.000 description 1
- 210000004993 mammalian placenta Anatomy 0.000 description 1
- 230000008774 maternal effect Effects 0.000 description 1
- 239000012982 microporous membrane Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 description 1
- 235000019171 pyridoxine hydrochloride Nutrition 0.000 description 1
- 239000011764 pyridoxine hydrochloride Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 239000006208 topical dosage form Substances 0.000 description 1
- 210000003954 umbilical cord Anatomy 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 229940011671 vitamin b6 Drugs 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
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
- A61K35/48—Reproductive organs
- A61K35/51—Umbilical cord; Umbilical cord blood; Umbilical stem cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- 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
- C12N5/0623—Stem cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- 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
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/03—Coculture with; Conditioned medium produced by non-embryonic pluripotent 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
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Neurology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Neurosurgery (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Developmental Biology & Embryology (AREA)
- Cell Biology (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Psychology (AREA)
- Virology (AREA)
- Immunology (AREA)
- Reproductive Health (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
Abstract
【解決手段】本発明の方法に従って臍帯血から分離・培養して得た間葉系幹細胞は神経前駆細胞又は神経幹細胞を神経細胞として分化及び増殖させるので、本発明の間葉系幹細胞及びこれを含む組成物は脳卒中、パーキンソン病、アルツハイマー病、ピック病、ハンチントン病、筋萎縮性側索硬化症、外傷性中枢神経系疾患及び脊髄損傷疾患を含む神経損傷疾患に対する細胞治療に有効に使用できる。
【選択図】図1
Description
また、本発明は、神経細胞損傷疾患の治療が必要な対象の神経細胞損傷部位に臍帯血由来間葉系幹細胞又はこれを含む組成物を投与する段階を含む、神経損傷疾患の治療方法を提供する。前記対象はヒトを含む哺乳動物でありうる。
ステップ1)臍帯血(umbilical cord blood, UCB)の収得
臍帯血のサンプルは、同意の下、産母の臍静脈から収得した。具体的には、44mlのCPDA-A抗凝固剤(ミドリ十字)を含んでいるUCB収集バック(collection bag)の16ゲージの注射針を臍静脈に挿入してUCBが収集バックに流れるようにした。収集された血液を48時間以内に処理し、細胞の生存率は90%以上であった。
ステップ1で得た臍帯血をフィコール・ハイパックグラディエント(密度:1.077g/ml、シグマ(Sigma)社)で遠心分離して単球細胞を収得した。そうした後、前記単核球細胞を数回洗浄して不純物を除去し、5乃至15重量%のFBS(ハイクローン(HyClone)社)を含む最小基本培地(α-MEM、ギブコ(Gibco BRL)社)に懸濁した。その後、予め計量された量の懸濁液を上記と同じ培地に添加し、5%の二酸化炭素インキュベータに37℃で一週間に2回ずつ培地を交換しながら培養した。培養された細胞が単一層を形成すると、顕微鏡でスピンドル模様を有する間葉系幹細胞の生成を確認した。その後、前記形成された間葉系幹細胞を、細胞が充分に増殖されるまで繰り返して継代培養した(Yang SE et al., Cytotherapy, 6(5):476-486, 2004)。
生理学的及び形態学的に神経前駆細胞と類似した特性を有するマウス脳由来のNG108-15細胞(Neuroblastoma X glioma hybrid)(ATCC, Cat. No. ATCC-CRL-HB-12317)を、DEME(Dulbecco’s modified Eagle’s medium)(4 mM/Lグルタミン、4.5g/Lグルコース、4.0mg/Lピリドキシン-HCl、0.1mMヒポキサンチン・グアニン、400nMアミノプテリン、0.016mMチミジン、5乃至15重量%ウシ胎児血清)で培養した。
マウス胎児の脳皮質由来の神経幹細胞(Chemicon, Cat. No. SCR029)を神経幹細胞基本培地(Neural stem cell basal medium)(20ng/ml FGF-2、20ng/ml EGF及び2mg/mlヘパリン)で培養した。
実施例1のヒト臍帯血由来間葉系幹細胞(hUCB-MSCs)をトランスウェルチャンバー(図1参照)及び実施例2の培養培地を用いて実施例2のNG108-15(hUCB-MSCs:NG108-15=1:1)と共同培養した。対照群として、NG108-15を単独で実施例2の培養培地で培養した。図1に示されたように、トランスウェルチャンバーは1μmの孔を有する微細孔膜(microporous membrane)によって互いに分離された下部(lower compartment)及び上部(upper compartment)で構成されている。hUCB-MSCは上部に、NG108-15は下部に配置した。
実施例1の方法で、他の2つの個体から間葉系幹細胞(hUCB-MSCs-1及びhUCB-MSCs-2)を収得した。実施例4と同じ方法で実施例2のNG108-15を単独で培養したり、hUCB-MSCs-1又はhUCB-MSCs-2と共同で7日間培養した。位相差顕微鏡(×100)で前記細胞の分化及び増殖を観察した。
実施例3の神経幹細胞を、トランスウェルチャンバーを用いて実施例3の培地で単独で培養するか(対照群)、実施例5のhUCB-MSCs-1又はhUCB-MSCs-2と共同で培養した。hUCB-MSCsは上部に、神経幹細胞は下部に配置した。
実施例3の神経幹細胞を、トランスウェルチャンバーを用いて実施例3の培地で単独で培養するか(対照群)、実施例1のhUCB-MSCsと共同で培養した(hUCB-MSCs:神経幹細胞=1:1)。hUCB-MSCsは上部に、前記神経幹細胞は下部に配置した。
各々実施例4及び6の方法に従って、実施例2のNG108-15を単独で培養するか(対照群)、実施例1のhUCB-MSCsと共同で培養して、実施例3の神経幹細胞を単独で培養するか(対照群)、実施例5のhUCB-MSCs-1及びhUCB-MSCs-2と共同で培養した。7日後に、トリパンブルー染色法(trypan blue staining)を用い、生きている細胞の数を測定した(図7及び図8参照)。
図7及び図8に示したように、NG108-15及び神経幹細胞の数は、共同培養した間葉系幹細胞の濃度に従って増加し、これは、臍帯血由来間葉系幹細胞が神経前駆細胞の神経細胞への分化を誘導するのに効果的であるだけではなく、それと同時に、神経細胞の数を増加させ、前記効果を持続且つ向上させるのに効果的であるということを示している。
Claims (6)
- 臍帯血由来の間葉系幹細胞を神経前駆細胞又は神経幹細胞と共同培養することを含む、神経前駆細胞又は神経幹細胞の神経細胞への分化及び増殖の誘導方法。
- 請求項1において、
前記臍帯血由来間葉系幹細胞と神経前駆細胞又は神経幹細胞の比率が1:0.1乃至1:10で
あることを特徴とする方法。 - 臍帯血由来間葉系幹細胞を含み、神経損傷疾患の治療を必要とする対象の神経細胞損傷部位に投与される薬学的製剤。
- 請求項3において、
前記神経損傷疾患が、脳卒中(stroke)、パーキンソン病、アルツハイマー病、ピック病(Pick’s disease)、ハンチントン病(Huntington’s disease)、筋萎縮性側索硬化症(amyotrophic lateral sclerosis)、外傷性中枢神経系疾患(traumatic central nervous system diseases)、及び脊髄損傷疾患(spinal cord injury disease)からなる群より選択される1つであることを特徴とする薬学的製剤。 - 請求項3において、
前記対象が、哺乳動物であることを特徴とする薬学的製剤。 - 臍帯血由来の間葉系幹細胞を有効成分として含む、神経前駆細胞又は神経幹細胞の神経細胞への分化及び増殖誘導用組成物。
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US86787506P | 2006-11-30 | 2006-11-30 | |
US60/867,875 | 2006-11-30 | ||
KR1020060120479A KR100959995B1 (ko) | 2006-12-01 | 2006-12-01 | 인간 제대혈 유래 간엽 줄기세포를 유효성분으로 포함하는,신경전구세포 또는 신경줄기세포의 신경세포로의 분화 및증식 유도용 조성물 |
KR10-2006-0120479 | 2006-12-01 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2009539185A Division JP2010511381A (ja) | 2006-11-30 | 2007-11-29 | 神経前駆細胞又は神経幹細胞の神経細胞への分化及び増殖の誘導方法、分化及び増殖誘導用組成物、及び薬学的製剤 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2013226159A true JP2013226159A (ja) | 2013-11-07 |
JP5871865B2 JP5871865B2 (ja) | 2016-03-01 |
Family
ID=39468070
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2009539185A Pending JP2010511381A (ja) | 2006-11-30 | 2007-11-29 | 神経前駆細胞又は神経幹細胞の神経細胞への分化及び増殖の誘導方法、分化及び増殖誘導用組成物、及び薬学的製剤 |
JP2013160426A Active JP5871865B2 (ja) | 2006-11-30 | 2013-08-01 | 神経前駆細胞又は神経幹細胞の神経細胞への分化及び増殖の誘導方法、分化及び増殖誘導用組成物、及び薬学的製剤 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2009539185A Pending JP2010511381A (ja) | 2006-11-30 | 2007-11-29 | 神経前駆細胞又は神経幹細胞の神経細胞への分化及び増殖の誘導方法、分化及び増殖誘導用組成物、及び薬学的製剤 |
Country Status (9)
Country | Link |
---|---|
US (2) | US9387226B2 (ja) |
EP (1) | EP2099901B1 (ja) |
JP (2) | JP2010511381A (ja) |
CN (1) | CN101541954B (ja) |
AU (1) | AU2007326171B2 (ja) |
CA (1) | CA2669304C (ja) |
HK (1) | HK1134688A1 (ja) |
MX (1) | MX2009005496A (ja) |
WO (1) | WO2008066330A1 (ja) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2019501970A (ja) * | 2015-12-30 | 2019-01-24 | ゴリオ,アルフレッド | 脂肪組織特性の促進と向上のための方法と、該方法で得られた組織と細胞 |
JPWO2017188457A1 (ja) * | 2016-04-28 | 2019-03-07 | 北海道公立大学法人 札幌医科大学 | シナプス形成剤 |
WO2022004822A1 (ja) * | 2020-06-30 | 2022-01-06 | 国立大学法人高知大学 | 胎児付属物由来組織細胞及び/又は臍帯血細胞を培養するための海洋深層水を含む培地 |
Families Citing this family (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10104880B2 (en) | 2008-08-20 | 2018-10-23 | Celularity, Inc. | Cell composition and methods of making the same |
CN101831401A (zh) * | 2010-04-23 | 2010-09-15 | 天津昂赛细胞基因工程有限公司 | 体外诱导间充质干细胞分化为神经干细胞的方法 |
US11286463B2 (en) | 2012-03-08 | 2022-03-29 | Advanced ReGen Medical Technologies, LLC | Reprogramming of aged adult stem cells |
KR20160018482A (ko) | 2013-04-09 | 2016-02-17 | 어드밴스드 리젠 메디컬 테크놀로지스, 엘엘씨 | 세포 회복을 위한 조성물 및 그의 제조 및 사용 방법 |
US10772911B2 (en) | 2013-12-20 | 2020-09-15 | Advanced ReGen Medical Technologies, LLC | Cell free compositions for cellular restoration and methods of making and using same |
CR20160307A (es) | 2013-12-20 | 2016-11-08 | Advanced Regen Medical Tech Llc | Composiciones para la restauración de células y métodos para la preparación y utilización de las mismas |
WO2015095895A1 (en) | 2013-12-20 | 2015-06-25 | Fred Hutchinson Cancer Research Center | Tagged chimeric effector molecules and receptors thereof |
WO2016068616A1 (ko) * | 2014-10-29 | 2016-05-06 | 차의과학대학교 산학협력단 | C3 또는 c1r 보체를 분비하는 태반 유래 세포 및 이를 포함하는 조성물 |
EP3288570A4 (en) | 2015-04-29 | 2018-11-21 | Fred Hutchinson Cancer Research Center | Modified stem cells and uses thereof |
US11110129B2 (en) | 2015-07-22 | 2021-09-07 | China Medical University | Method for treating multiple sclerosis |
TWI589698B (zh) | 2015-07-22 | 2017-07-01 | 中國醫藥大學 | 間質幹細胞、其純株化擴張之方法、其分離方法及其應用 |
CN106701668B (zh) * | 2015-07-22 | 2020-12-29 | 中国医药大学 | 间质干细胞、其纯株化扩张的方法及其应用 |
WO2017190000A1 (en) | 2016-04-29 | 2017-11-02 | Advanced ReGen Medical Technologies, LLC | Microrna compositions and methods of making and using same |
CN109415696A (zh) * | 2016-05-25 | 2019-03-01 | 泰尔茂比司特公司 | 细胞扩增 |
US10717981B2 (en) | 2018-01-18 | 2020-07-21 | Advanced ReGen Medical Technologies, LLC | Therapeutic compositions and methods of making and using the same |
WO2019237106A1 (en) * | 2018-06-08 | 2019-12-12 | University Of Virginia Patent Foundation | Compositions and methods for treating stroke |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1302534A1 (en) * | 2000-06-26 | 2003-04-16 | Renomedix Institute Inc. | Cell fraction containing cells capable of differentiating into neural cells |
Family Cites Families (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7354588B1 (en) | 1987-05-04 | 2008-04-08 | Dana Farber Cancer Institute | Functional derivatives of ICAM-1 with altered ability to bind LFA-1 or HRV |
US5733542A (en) | 1990-11-16 | 1998-03-31 | Haynesworth; Stephen E. | Enhancing bone marrow engraftment using MSCS |
US5837576A (en) | 1997-10-31 | 1998-11-17 | Vanguard International Semiconductor Corporation | Method for forming a capacitor using a silicon oxynitride etching stop layer |
US6900299B1 (en) | 1999-03-11 | 2005-05-31 | University Of South Florida | Interrupting the interaction of intercellular adhesion molecule-1 and respiratory syncytial virus for prevention and treatment of infection |
ATE308244T1 (de) | 1999-03-12 | 2005-11-15 | Univ Leland Stanford Junior | Dna-impfung zur behandlung von autoimmunerkrankungen |
US6372494B1 (en) | 1999-05-14 | 2002-04-16 | Advanced Tissue Sciences, Inc. | Methods of making conditioned cell culture medium compositions |
US20040208858A1 (en) | 2000-04-12 | 2004-10-21 | Gihan Tennekoon | Therapeutic uses for mesenchymal stromal cells |
US20040037775A1 (en) | 2000-08-01 | 2004-02-26 | Siahaan Teruna J. | Leukocyte internalized peptide-drug conjugates |
US7560280B2 (en) | 2000-11-03 | 2009-07-14 | Kourion Therapeutics Gmbh | Human cord blood derived unrestricted somatic stem cells (USSC) |
KR100449141B1 (ko) * | 2001-04-19 | 2004-09-21 | (주)라이프코드 | 간엽 간세포를 신경세포로 분화시키는 방법 |
DE60314602T2 (de) | 2002-02-19 | 2008-02-28 | Medipost, Co., Ltd. | Verfahren zur isolierung und kulturexpansion mesenchymaler stamm-/vorläuferzellen aus nabelschnurblut sowie verfahren zur differenzierung von aus nabelschnurblut stammenden mesenchymalen stamm-/vorläuferzellen in unterschiedliche mesenchymgewebe |
US20090192105A1 (en) | 2002-02-20 | 2009-07-30 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF INTERCELLULAR ADHESION MOLECULE (ICAM) GENE EXPRESSION USING SHORT INTERFERING NUCELIC ACID (siNA) |
WO2004016779A1 (en) | 2002-08-17 | 2004-02-26 | Hae-Young Suh | A method for transdifferentiating mesenchymal stem cells into neuronal cells |
US20040203142A1 (en) * | 2003-04-14 | 2004-10-14 | Reliance Life Sciences Pvt. Ltd. | Growth of neural precursor cells using umbilical cord blood serum and a process for the preparation thereof for therapeutic purposes |
WO2005026343A1 (ja) | 2003-09-09 | 2005-03-24 | Keio University | 神経幹細胞の生存及び/又は増殖及び神経突起伸張を促進する方法並びに促進剤、神経幹細胞を含む医薬組成物、検定方法、スクリーニング方法 |
US20060094064A1 (en) | 2003-11-19 | 2006-05-04 | Sandip Ray | Methods and compositions for diagnosis, stratification, and monitoring of alzheimer's disease and other neurological disorders in body fluids |
WO2007054128A1 (en) | 2005-11-14 | 2007-05-18 | Dominion Pharmakine S.L. | Novel inhibitors of the lfa-1/icam-1 interaction, and uses thereof |
EP1767617A1 (en) | 2005-09-26 | 2007-03-28 | Letizia Mazzini | Mesenchymal stem cells isolation and expansion method and uses thereof |
US20070253931A1 (en) | 2006-01-12 | 2007-11-01 | Osiris Therapeutics, Inc. | Use of mesenchymal stem cells for treating genetic diseases and disorders |
KR100792184B1 (ko) | 2006-05-12 | 2008-01-07 | 재단법인서울대학교산학협력재단 | 개의 제대혈, 태반 및 개 태아의 심장 유래 다분화능 성체줄기세포, 그 제조방법 및 이를 함유하는 세포 치료제 |
KR20080049562A (ko) | 2006-11-30 | 2008-06-04 | 가톨릭대학교 산학협력단 | 제대혈 유래 간엽 줄기세포를 유효성분으로 포함하는 신경손상 질환 치료제 |
KR20100054711A (ko) | 2008-11-14 | 2010-05-25 | 메디포스트(주) | 간엽 줄기세포 또는 이의 배양액을 포함하는 신경질환의 예방 또는 치료용 조성물 |
-
2007
- 2007-11-29 AU AU2007326171A patent/AU2007326171B2/en active Active
- 2007-11-29 WO PCT/KR2007/006084 patent/WO2008066330A1/en active Application Filing
- 2007-11-29 US US12/516,913 patent/US9387226B2/en active Active
- 2007-11-29 MX MX2009005496A patent/MX2009005496A/es active IP Right Grant
- 2007-11-29 EP EP07851154.0A patent/EP2099901B1/en active Active
- 2007-11-29 CN CN2007800440974A patent/CN101541954B/zh active Active
- 2007-11-29 CA CA2669304A patent/CA2669304C/en active Active
- 2007-11-29 JP JP2009539185A patent/JP2010511381A/ja active Pending
-
2010
- 2010-03-17 HK HK10102815.7A patent/HK1134688A1/xx unknown
-
2013
- 2013-08-01 JP JP2013160426A patent/JP5871865B2/ja active Active
- 2013-08-19 US US13/970,074 patent/US9439931B2/en active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1302534A1 (en) * | 2000-06-26 | 2003-04-16 | Renomedix Institute Inc. | Cell fraction containing cells capable of differentiating into neural cells |
Non-Patent Citations (2)
Title |
---|
JPN6012054594; Stem Cells,2006-OCT,24(10),p.2209-19 * |
JPN6012054596; Blood,2004,103(5),p.1669-75 * |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2019501970A (ja) * | 2015-12-30 | 2019-01-24 | ゴリオ,アルフレッド | 脂肪組織特性の促進と向上のための方法と、該方法で得られた組織と細胞 |
JPWO2017188457A1 (ja) * | 2016-04-28 | 2019-03-07 | 北海道公立大学法人 札幌医科大学 | シナプス形成剤 |
JP7101367B2 (ja) | 2016-04-28 | 2022-07-15 | 北海道公立大学法人 札幌医科大学 | シナプス形成剤 |
JP2022126812A (ja) * | 2016-04-28 | 2022-08-30 | 北海道公立大学法人 札幌医科大学 | シナプス形成剤 |
US11666601B2 (en) | 2016-04-28 | 2023-06-06 | Sapporo Medical University | Synapse formation agent |
JP7450896B2 (ja) | 2016-04-28 | 2024-03-18 | 北海道公立大学法人 札幌医科大学 | シナプス形成剤 |
WO2022004822A1 (ja) * | 2020-06-30 | 2022-01-06 | 国立大学法人高知大学 | 胎児付属物由来組織細胞及び/又は臍帯血細胞を培養するための海洋深層水を含む培地 |
Also Published As
Publication number | Publication date |
---|---|
MX2009005496A (es) | 2009-06-03 |
EP2099901B1 (en) | 2015-09-09 |
US9387226B2 (en) | 2016-07-12 |
EP2099901A4 (en) | 2010-01-13 |
EP2099901A1 (en) | 2009-09-16 |
CA2669304C (en) | 2016-10-25 |
WO2008066330A8 (en) | 2009-05-28 |
JP5871865B2 (ja) | 2016-03-01 |
CN101541954A (zh) | 2009-09-23 |
US20130330306A1 (en) | 2013-12-12 |
CA2669304A1 (en) | 2008-06-05 |
HK1134688A1 (en) | 2010-05-07 |
US9439931B2 (en) | 2016-09-13 |
JP2010511381A (ja) | 2010-04-15 |
AU2007326171A1 (en) | 2008-06-05 |
AU2007326171B2 (en) | 2012-11-15 |
CN101541954B (zh) | 2012-12-26 |
US20100074875A1 (en) | 2010-03-25 |
WO2008066330A1 (en) | 2008-06-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5871865B2 (ja) | 神経前駆細胞又は神経幹細胞の神経細胞への分化及び増殖の誘導方法、分化及び増殖誘導用組成物、及び薬学的製剤 | |
JP7441079B2 (ja) | 神経変性を治療するための方法及び組成物 | |
JP3976190B2 (ja) | 間葉系幹細胞を神経細胞に分化させる方法 | |
KR100959995B1 (ko) | 인간 제대혈 유래 간엽 줄기세포를 유효성분으로 포함하는,신경전구세포 또는 신경줄기세포의 신경세포로의 분화 및증식 유도용 조성물 | |
WO2018103406A1 (zh) | 一种治疗脑部损伤类疾病的神经干细胞注射液及其制备方法和使用方法 | |
KR20090055691A (ko) | 인간 제대혈 유래 간엽 줄기세포를 유효성분으로 포함하는,신경전구세포 또는 신경줄기세포의 신경세포로의 분화 및증식 유도용 조성물 | |
US7635591B2 (en) | Method for differentiating mesenchymal stem cell into neural cell and pharmaceutical composition containing the neural cell for neurodegenerative disease | |
EP2063902A1 (en) | Therapeutic cell medicine comprising skin tissue derived stem cell | |
Mao et al. | Skin-derived precursor cells promote angiogenesis and stimulate proliferation of endogenous neural stem cells after cerebral infarction | |
EP3508207B1 (en) | Cell preparations cultivated under low oxygen and sugar conditions, and their uses in therapy. | |
CN113388580B (zh) | 一种诱导脂肪干细胞分化为功能性多巴胺能神经元的方法及用途 | |
CN111566204A (zh) | 培养细胞的制造方法、脊髓损伤疾病的治疗剂的制造方法 | |
TW201444973A (zh) | 用於治療神經退化的細胞療法 | |
WO2003060107A1 (fr) | Separation, preparation et utilisation de cellules souches de ganglions spinaux (drg) d'embryons humains | |
CN118064356A (zh) | 前脑神经前体细胞在治疗与前脑神经细胞的死亡和/或功能不全相关的疾病中的应用 | |
KR20150062817A (ko) | 태반의 융모막 또는 와튼제대교질 유래 간엽줄기세포로부터 신경세포 및 유모세포를 분화시키는 방법 | |
Mao et al. | Research Article Skin-Derived Precursor Cells Promote Angiogenesis and Stimulate Proliferation of Endogenous Neural Stem Cells after Cerebral Infarction | |
JPWO2003018041A1 (ja) | 脊髄損傷の治療方法及びそのための治療剤 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20130801 |
|
RD01 | Notification of change of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7426 Effective date: 20130909 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20130909 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20141118 |
|
A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20150216 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20150609 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150825 |
|
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: 20160105 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20160112 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5871865 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
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 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |