JP2006522604A - 化学誘引物質に対する増大させた感受性を有する幹細胞およびそれを産生および使用する方法 - Google Patents
化学誘引物質に対する増大させた感受性を有する幹細胞およびそれを産生および使用する方法 Download PDFInfo
- Publication number
- JP2006522604A JP2006522604A JP2006507603A JP2006507603A JP2006522604A JP 2006522604 A JP2006522604 A JP 2006522604A JP 2006507603 A JP2006507603 A JP 2006507603A JP 2006507603 A JP2006507603 A JP 2006507603A JP 2006522604 A JP2006522604 A JP 2006522604A
- Authority
- JP
- Japan
- Prior art keywords
- stem cells
- cell
- hgf
- stem cell
- cells
- 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
- 210000000130 stem cell Anatomy 0.000 title claims abstract description 209
- 238000000034 method Methods 0.000 title claims abstract description 111
- 230000001965 increasing effect Effects 0.000 title claims abstract description 54
- 239000002975 chemoattractant Substances 0.000 title claims abstract description 24
- 230000035945 sensitivity Effects 0.000 title claims description 19
- 238000004519 manufacturing process Methods 0.000 claims abstract description 6
- 210000004027 cell Anatomy 0.000 claims description 149
- 210000003958 hematopoietic stem cell Anatomy 0.000 claims description 91
- 210000001519 tissue Anatomy 0.000 claims description 44
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 claims description 37
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 claims description 35
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 claims description 35
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 claims description 33
- 210000001185 bone marrow Anatomy 0.000 claims description 33
- 102000004127 Cytokines Human genes 0.000 claims description 29
- 108090000695 Cytokines Proteins 0.000 claims description 29
- 210000004185 liver Anatomy 0.000 claims description 26
- 108091033319 polynucleotide Proteins 0.000 claims description 21
- 102000040430 polynucleotide Human genes 0.000 claims description 21
- 239000002157 polynucleotide Substances 0.000 claims description 21
- 102000011652 Formyl peptide receptors Human genes 0.000 claims description 20
- 108010076288 Formyl peptide receptors Proteins 0.000 claims description 20
- 239000003102 growth factor Substances 0.000 claims description 20
- 210000000056 organ Anatomy 0.000 claims description 20
- 210000002901 mesenchymal stem cell Anatomy 0.000 claims description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 208000035475 disorder Diseases 0.000 claims description 17
- 230000006378 damage Effects 0.000 claims description 12
- 230000000694 effects Effects 0.000 claims description 12
- 238000004113 cell culture Methods 0.000 claims description 10
- 150000007523 nucleic acids Chemical class 0.000 claims description 10
- 238000002054 transplantation Methods 0.000 claims description 10
- 108090001005 Interleukin-6 Proteins 0.000 claims description 9
- 208000027418 Wounds and injury Diseases 0.000 claims description 9
- 208000014674 injury Diseases 0.000 claims description 9
- 230000004899 motility Effects 0.000 claims description 9
- 102000039446 nucleic acids Human genes 0.000 claims description 9
- 108020004707 nucleic acids Proteins 0.000 claims description 9
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 claims description 8
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 claims description 8
- 230000009087 cell motility Effects 0.000 claims description 8
- 206010061218 Inflammation Diseases 0.000 claims description 7
- 230000004054 inflammatory process Effects 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 230000001737 promoting effect Effects 0.000 claims description 7
- 102000027430 HGF receptors Human genes 0.000 claims description 6
- 108091008603 HGF receptors Proteins 0.000 claims description 6
- 210000000988 bone and bone Anatomy 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 230000001939 inductive effect Effects 0.000 claims description 5
- 238000001943 fluorescence-activated cell sorting Methods 0.000 claims description 4
- 108010076504 Protein Sorting Signals Proteins 0.000 claims description 2
- 210000000653 nervous system Anatomy 0.000 claims description 2
- 210000000496 pancreas Anatomy 0.000 claims description 2
- 230000028327 secretion Effects 0.000 claims description 2
- 210000002027 skeletal muscle Anatomy 0.000 claims description 2
- 210000004204 blood vessel Anatomy 0.000 claims 1
- 210000002216 heart Anatomy 0.000 claims 1
- 210000003734 kidney Anatomy 0.000 claims 1
- 210000004072 lung Anatomy 0.000 claims 1
- 210000003491 skin Anatomy 0.000 claims 1
- 230000001747 exhibiting effect Effects 0.000 abstract description 7
- 238000011476 stem cell transplantation Methods 0.000 abstract description 5
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 description 138
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 138
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 48
- 108090000623 proteins and genes Proteins 0.000 description 37
- 102000004169 proteins and genes Human genes 0.000 description 32
- 235000018102 proteins Nutrition 0.000 description 30
- 241000699670 Mus sp. Species 0.000 description 23
- 238000013508 migration Methods 0.000 description 23
- 230000005012 migration Effects 0.000 description 20
- 108090000765 processed proteins & peptides Proteins 0.000 description 19
- 235000001014 amino acid Nutrition 0.000 description 18
- 239000002243 precursor Substances 0.000 description 18
- 102000004196 processed proteins & peptides Human genes 0.000 description 17
- 150000001413 amino acids Chemical class 0.000 description 15
- 210000004369 blood Anatomy 0.000 description 15
- 239000008280 blood Substances 0.000 description 15
- 229920001184 polypeptide Polymers 0.000 description 15
- 150000003839 salts Chemical class 0.000 description 14
- 238000011282 treatment Methods 0.000 description 14
- 210000002798 bone marrow cell Anatomy 0.000 description 13
- 238000009396 hybridization Methods 0.000 description 13
- 102000005962 receptors Human genes 0.000 description 13
- 108020003175 receptors Proteins 0.000 description 13
- 241000699666 Mus <mouse, genus> Species 0.000 description 11
- -1 no more than 50 Chemical class 0.000 description 11
- 108020004414 DNA Proteins 0.000 description 10
- 230000012292 cell migration Effects 0.000 description 10
- 230000035605 chemotaxis Effects 0.000 description 9
- 210000004700 fetal blood Anatomy 0.000 description 9
- 108020004999 messenger RNA Proteins 0.000 description 9
- 125000003275 alpha amino acid group Chemical group 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 239000001963 growth medium Substances 0.000 description 8
- 230000003993 interaction Effects 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 238000011579 SCID mouse model Methods 0.000 description 7
- 210000002459 blastocyst Anatomy 0.000 description 7
- 230000003399 chemotactic effect Effects 0.000 description 7
- 239000012634 fragment Substances 0.000 description 7
- 238000000338 in vitro Methods 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 6
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 6
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 6
- 206010067125 Liver injury Diseases 0.000 description 6
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 6
- 102000008300 Mutant Proteins Human genes 0.000 description 6
- 108010021466 Mutant Proteins Proteins 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 230000012010 growth Effects 0.000 description 6
- 230000003394 haemopoietic effect Effects 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 5
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 5
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 5
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 5
- 125000000539 amino acid group Chemical group 0.000 description 5
- 230000004087 circulation Effects 0.000 description 5
- 230000001419 dependent effect Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 238000010369 molecular cloning Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 101710082513 C-X-C chemokine receptor type 4 Proteins 0.000 description 4
- 108010012236 Chemokines Proteins 0.000 description 4
- 102000019034 Chemokines Human genes 0.000 description 4
- 241001529297 Coregonus peled Species 0.000 description 4
- 101100220044 Homo sapiens CD34 gene Proteins 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 230000003466 anti-cipated effect Effects 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000017531 blood circulation Effects 0.000 description 4
- 210000004271 bone marrow stromal cell Anatomy 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 230000010261 cell growth Effects 0.000 description 4
- 210000002808 connective tissue Anatomy 0.000 description 4
- 230000007547 defect Effects 0.000 description 4
- 230000007812 deficiency Effects 0.000 description 4
- 230000004069 differentiation Effects 0.000 description 4
- 230000007646 directional migration Effects 0.000 description 4
- 210000001671 embryonic stem cell Anatomy 0.000 description 4
- 239000013604 expression vector Substances 0.000 description 4
- 102000037865 fusion proteins Human genes 0.000 description 4
- 108020001507 fusion proteins Proteins 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 230000035935 pregnancy Effects 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 230000003827 upregulation Effects 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 102000007469 Actins Human genes 0.000 description 3
- 108010085238 Actins Proteins 0.000 description 3
- 241000283707 Capra Species 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 3
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 3
- 108010063738 Interleukins Proteins 0.000 description 3
- 102000015696 Interleukins Human genes 0.000 description 3
- UYDDNEYNGGSTDW-OYDLWJJNSA-N Met-Trp-Trp Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](CC3=CNC4=CC=CC=C43)C(=O)O)N UYDDNEYNGGSTDW-OYDLWJJNSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 3
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 210000004504 adult stem cell Anatomy 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 210000000845 cartilage Anatomy 0.000 description 3
- 238000002659 cell therapy Methods 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 238000012258 culturing Methods 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 230000003436 cytoskeletal effect Effects 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 210000003527 eukaryotic cell Anatomy 0.000 description 3
- 230000001605 fetal effect Effects 0.000 description 3
- 238000000684 flow cytometry Methods 0.000 description 3
- 210000003494 hepatocyte Anatomy 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 208000032839 leukemia Diseases 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 238000010232 migration assay Methods 0.000 description 3
- 210000005259 peripheral blood Anatomy 0.000 description 3
- 239000011886 peripheral blood Substances 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 239000007790 solid phase Substances 0.000 description 3
- 238000010532 solid phase synthesis reaction Methods 0.000 description 3
- 238000009168 stem cell therapy Methods 0.000 description 3
- 238000009580 stem-cell therapy Methods 0.000 description 3
- 210000002536 stromal cell Anatomy 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 230000014616 translation Effects 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 2
- 102000055025 Adenosine deaminases Human genes 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 206010010356 Congenital anomaly Diseases 0.000 description 2
- YXQDRIRSAHTJKM-IMJSIDKUSA-N Cys-Ser Chemical compound SC[C@H](N)C(=O)N[C@@H](CO)C(O)=O YXQDRIRSAHTJKM-IMJSIDKUSA-N 0.000 description 2
- IMROMDMJAWUWLK-UHFFFAOYSA-N Ethenol Chemical compound OC=C IMROMDMJAWUWLK-UHFFFAOYSA-N 0.000 description 2
- 108091006027 G proteins Proteins 0.000 description 2
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 2
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 2
- 102000030782 GTP binding Human genes 0.000 description 2
- 108091000058 GTP-Binding Proteins 0.000 description 2
- XEKAJTCACGEBOK-KKUMJFAQSA-N Glu-Met-Phe Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CCC(=O)O)N XEKAJTCACGEBOK-KKUMJFAQSA-N 0.000 description 2
- SWSVTNGMKBDTBM-DCAQKATOSA-N His-Gln-Glu Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N SWSVTNGMKBDTBM-DCAQKATOSA-N 0.000 description 2
- 101000958041 Homo sapiens Musculin Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 108010002386 Interleukin-3 Proteins 0.000 description 2
- OKIZCWYLBDKLSU-UHFFFAOYSA-M N,N,N-Trimethylmethanaminium chloride Chemical compound [Cl-].C[N+](C)(C)C OKIZCWYLBDKLSU-UHFFFAOYSA-M 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 208000023940 X-Linked Combined Immunodeficiency disease Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000000735 allogeneic effect Effects 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 210000003969 blast cell Anatomy 0.000 description 2
- 238000010322 bone marrow transplantation Methods 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 230000006041 cell recruitment Effects 0.000 description 2
- 210000004748 cultured cell Anatomy 0.000 description 2
- 230000002380 cytological effect Effects 0.000 description 2
- 238000010494 dissociation reaction Methods 0.000 description 2
- 230000005593 dissociations Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 210000002257 embryonic structure Anatomy 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 238000002825 functional assay Methods 0.000 description 2
- 238000012239 gene modification Methods 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 230000005017 genetic modification Effects 0.000 description 2
- 235000013617 genetically modified food Nutrition 0.000 description 2
- 210000000777 hematopoietic system Anatomy 0.000 description 2
- 231100000234 hepatic damage Toxicity 0.000 description 2
- 230000002440 hepatic effect Effects 0.000 description 2
- 102000046949 human MSC Human genes 0.000 description 2
- 238000003125 immunofluorescent labeling Methods 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 102000006495 integrins Human genes 0.000 description 2
- 108010044426 integrins Proteins 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 230000008818 liver damage Effects 0.000 description 2
- 230000033001 locomotion Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000037230 mobility Effects 0.000 description 2
- 230000004001 molecular interaction Effects 0.000 description 2
- 210000001178 neural stem cell Anatomy 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 238000001742 protein purification Methods 0.000 description 2
- 210000001243 pseudopodia Anatomy 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 238000007634 remodeling Methods 0.000 description 2
- 230000008521 reorganization Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 208000002491 severe combined immunodeficiency Diseases 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- UKUVVAMSXXBMRX-UHFFFAOYSA-N 2,4,5-trithia-1,3-diarsabicyclo[1.1.1]pentane Chemical compound S1[As]2S[As]1S2 UKUVVAMSXXBMRX-UHFFFAOYSA-N 0.000 description 1
- NMUSYJAQQFHJEW-UHFFFAOYSA-N 5-Azacytidine Natural products O=C1N=C(N)N=CN1C1C(O)C(O)C(CO)O1 NMUSYJAQQFHJEW-UHFFFAOYSA-N 0.000 description 1
- NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- GMRGSBAMMMVDGG-GUBZILKMSA-N Asn-Arg-Arg Chemical compound C(C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CC(=O)N)N)CN=C(N)N GMRGSBAMMMVDGG-GUBZILKMSA-N 0.000 description 1
- ALHMNHZJBYBYHS-DCAQKATOSA-N Asn-Lys-Arg Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O ALHMNHZJBYBYHS-DCAQKATOSA-N 0.000 description 1
- FBODFHMLALOPHP-GUBZILKMSA-N Asn-Lys-Glu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O FBODFHMLALOPHP-GUBZILKMSA-N 0.000 description 1
- ZYPWIUFLYMQZBS-SRVKXCTJSA-N Asn-Lys-Lys Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)N)N ZYPWIUFLYMQZBS-SRVKXCTJSA-N 0.000 description 1
- WCFCYFDBMNFSPA-ACZMJKKPSA-N Asp-Asp-Glu Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCC(O)=O WCFCYFDBMNFSPA-ACZMJKKPSA-N 0.000 description 1
- CKAJHWFHHFSCDT-WHFBIAKZSA-N Asp-Glu Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(O)=O CKAJHWFHHFSCDT-WHFBIAKZSA-N 0.000 description 1
- XAJRHVUUVUPFQL-ACZMJKKPSA-N Asp-Glu-Asp Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O XAJRHVUUVUPFQL-ACZMJKKPSA-N 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 101100454433 Biomphalaria glabrata BG01 gene Proteins 0.000 description 1
- 101100454434 Biomphalaria glabrata BG04 gene Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 1
- 102100039398 C-X-C motif chemokine 2 Human genes 0.000 description 1
- 102000009135 CB2 Cannabinoid Receptor Human genes 0.000 description 1
- 108010073376 CB2 Cannabinoid Receptor Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 108010008951 Chemokine CXCL12 Proteins 0.000 description 1
- 102000009410 Chemokine receptor Human genes 0.000 description 1
- 108050000299 Chemokine receptor Proteins 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108700010070 Codon Usage Proteins 0.000 description 1
- 206010010099 Combined immunodeficiency Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 108010062580 Concanavalin A Proteins 0.000 description 1
- 208000032170 Congenital Abnormalities Diseases 0.000 description 1
- ANPADMNVVOOYKW-DCAQKATOSA-N Cys-His-Arg Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O ANPADMNVVOOYKW-DCAQKATOSA-N 0.000 description 1
- KPENUVBHAKRDQR-GUBZILKMSA-N Cys-His-Glu Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(O)=O)C(O)=O KPENUVBHAKRDQR-GUBZILKMSA-N 0.000 description 1
- OWAFTBLVZNSIFO-SRVKXCTJSA-N Cys-His-His Chemical compound N[C@@H](CS)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](Cc1cnc[nH]1)C(O)=O OWAFTBLVZNSIFO-SRVKXCTJSA-N 0.000 description 1
- 102000010918 Cysteinyl leukotriene receptors Human genes 0.000 description 1
- 108050001116 Cysteinyl leukotriene receptors Proteins 0.000 description 1
- 208000010334 End Stage Liver Disease Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102100037362 Fibronectin Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 208000015872 Gaucher disease Diseases 0.000 description 1
- 102000034354 Gi proteins Human genes 0.000 description 1
- 108091006101 Gi proteins Proteins 0.000 description 1
- RRYLMJWPWBJFPZ-ACZMJKKPSA-N Gln-Asn-Asp Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC(=O)O)C(=O)O)N RRYLMJWPWBJFPZ-ACZMJKKPSA-N 0.000 description 1
- TWHDOEYLXXQYOZ-FXQIFTODSA-N Gln-Asn-Gln Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N TWHDOEYLXXQYOZ-FXQIFTODSA-N 0.000 description 1
- CITDWMLWXNUQKD-FXQIFTODSA-N Gln-Gln-Asn Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(=O)N)C(=O)O)N CITDWMLWXNUQKD-FXQIFTODSA-N 0.000 description 1
- LKOAAMXDJGEYMS-ZPFDUUQYSA-N Glu-Met-Ile Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O LKOAAMXDJGEYMS-ZPFDUUQYSA-N 0.000 description 1
- ZOTGXWMKUFSKEU-QXEWZRGKSA-N Gly-Ile-Met Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCSC)C(O)=O ZOTGXWMKUFSKEU-QXEWZRGKSA-N 0.000 description 1
- 101150022655 HGF gene Proteins 0.000 description 1
- 102000008055 Heparan Sulfate Proteoglycans Human genes 0.000 description 1
- 229920002971 Heparan sulfate Polymers 0.000 description 1
- 206010019663 Hepatic failure Diseases 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- BXOLYFJYQQRQDJ-MXAVVETBSA-N His-Leu-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CN=CN1)N BXOLYFJYQQRQDJ-MXAVVETBSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000889128 Homo sapiens C-X-C motif chemokine 2 Proteins 0.000 description 1
- 101000898034 Homo sapiens Hepatocyte growth factor Proteins 0.000 description 1
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- KLJKJVXDHVUMMZ-KKPKCPPISA-N Ile-Phe-Trp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)O)N KLJKJVXDHVUMMZ-KKPKCPPISA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 102000012355 Integrin beta1 Human genes 0.000 description 1
- 108010022222 Integrin beta1 Proteins 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- WXDRGWBQZIMJDE-ULQDDVLXSA-N Leu-Phe-Met Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCSC)C(O)=O WXDRGWBQZIMJDE-ULQDDVLXSA-N 0.000 description 1
- WMIOEVKKYIMVKI-DCAQKATOSA-N Leu-Pro-Ala Chemical compound [H]N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O WMIOEVKKYIMVKI-DCAQKATOSA-N 0.000 description 1
- UCBPDSYUVAAHCD-UWVGGRQHSA-N Leu-Pro-Gly Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O UCBPDSYUVAAHCD-UWVGGRQHSA-N 0.000 description 1
- DPURXCQCHSQPAN-AVGNSLFASA-N Leu-Pro-Pro Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 DPURXCQCHSQPAN-AVGNSLFASA-N 0.000 description 1
- KPJJOZUXFOLGMQ-CIUDSAMLSA-N Lys-Asp-Asn Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)N KPJJOZUXFOLGMQ-CIUDSAMLSA-N 0.000 description 1
- OVIVOCSURJYCTM-GUBZILKMSA-N Lys-Asp-Glu Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCC(O)=O OVIVOCSURJYCTM-GUBZILKMSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 229920002858 MOWIOL ® 4-88 Polymers 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 102000008763 Neurofilament Proteins Human genes 0.000 description 1
- 108010088373 Neurofilament Proteins Proteins 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 108020005187 Oligonucleotide Probes Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 208000035467 Pancreatic insufficiency Diseases 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 208000006735 Periostitis Diseases 0.000 description 1
- IPVPGAADZXRZSH-RNXOBYDBSA-N Phe-Tyr-Trp Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O IPVPGAADZXRZSH-RNXOBYDBSA-N 0.000 description 1
- 102000013566 Plasminogen Human genes 0.000 description 1
- 108010051456 Plasminogen Proteins 0.000 description 1
- AIOWVDNPESPXRB-YTWAJWBKSA-N Pro-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@@H]2CCCN2)O AIOWVDNPESPXRB-YTWAJWBKSA-N 0.000 description 1
- GZNYIXWOIUFLGO-ZJDVBMNYSA-N Pro-Thr-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GZNYIXWOIUFLGO-ZJDVBMNYSA-N 0.000 description 1
- 101710093543 Probable non-specific lipid-transfer protein Proteins 0.000 description 1
- 102000052575 Proto-Oncogene Human genes 0.000 description 1
- 108700020978 Proto-Oncogene Proteins 0.000 description 1
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- XZKQVQKUZMAADP-IMJSIDKUSA-N Ser-Ser Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(O)=O XZKQVQKUZMAADP-IMJSIDKUSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 108050001286 Somatostatin Receptor Proteins 0.000 description 1
- 102000011096 Somatostatin receptor Human genes 0.000 description 1
- 102100021669 Stromal cell-derived factor 1 Human genes 0.000 description 1
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 1
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 108090000054 Syndecan-2 Proteins 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 208000002903 Thalassemia Diseases 0.000 description 1
- TYVAWPFQYFPSBR-BFHQHQDPSA-N Thr-Ala-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)NCC(O)=O TYVAWPFQYFPSBR-BFHQHQDPSA-N 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- ZAGPDPNPWYPEIR-SRVKXCTJSA-N Tyr-Cys-Ser Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(O)=O ZAGPDPNPWYPEIR-SRVKXCTJSA-N 0.000 description 1
- CELJCNRXKZPTCX-XPUUQOCRSA-N Val-Gly-Ala Chemical compound CC(C)[C@H](N)C(=O)NCC(=O)N[C@@H](C)C(O)=O CELJCNRXKZPTCX-XPUUQOCRSA-N 0.000 description 1
- PIFJAFRUVWZRKR-QMMMGPOBSA-N Val-Gly-Gly Chemical compound CC(C)[C@H]([NH3+])C(=O)NCC(=O)NCC([O-])=O PIFJAFRUVWZRKR-QMMMGPOBSA-N 0.000 description 1
- AEFJNECXZCODJM-UWVGGRQHSA-N Val-Val-Gly Chemical compound CC(C)[C@H]([NH3+])C(=O)N[C@@H](C(C)C)C(=O)NCC([O-])=O AEFJNECXZCODJM-UWVGGRQHSA-N 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 239000005862 Whey Substances 0.000 description 1
- 102000007544 Whey Proteins Human genes 0.000 description 1
- 108010046377 Whey Proteins Proteins 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 231100000439 acute liver injury Toxicity 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 108010087924 alanylproline Proteins 0.000 description 1
- 150000008431 aliphatic amides Chemical class 0.000 description 1
- KOSRFJWDECSPRO-UHFFFAOYSA-N alpha-L-glutamyl-L-glutamic acid Natural products OC(=O)CCC(N)C(=O)NC(CCC(O)=O)C(O)=O KOSRFJWDECSPRO-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000003435 aroyl group Chemical group 0.000 description 1
- 108010038633 aspartylglutamate Proteins 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 229960002756 azacitidine Drugs 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 238000007413 biotinylation Methods 0.000 description 1
- 230000006287 biotinylation Effects 0.000 description 1
- 230000007698 birth defect Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009583 bone marrow aspiration Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
- 229940043253 butylated hydroxyanisole Drugs 0.000 description 1
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 210000001043 capillary endothelial cell Anatomy 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 230000032341 cell morphogenesis Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000005482 chemotactic factor Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 210000001612 chondrocyte Anatomy 0.000 description 1
- 230000002648 chondrogenic effect Effects 0.000 description 1
- 238000011098 chromatofocusing Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000011444 chronic liver failure Diseases 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000008175 fetal development Effects 0.000 description 1
- 210000003754 fetus Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 108700014844 flt3 ligand Proteins 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 238000001641 gel filtration chromatography Methods 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 210000001654 germ layer Anatomy 0.000 description 1
- 108010055341 glutamyl-glutamic acid Proteins 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 230000017323 hematopoietic stem cell migration to bone marrow Effects 0.000 description 1
- 231100000753 hepatic injury Toxicity 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 102000057308 human HGF Human genes 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 210000001822 immobilized cell Anatomy 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 108010073472 leucyl-prolyl-proline Proteins 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 208000007903 liver failure Diseases 0.000 description 1
- 231100000835 liver failure Toxicity 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 210000003593 megakaryocyte Anatomy 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 102000035118 modified proteins Human genes 0.000 description 1
- 108091005573 modified proteins Proteins 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 230000000921 morphogenic effect Effects 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 238000011527 multiparameter analysis Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 210000005044 neurofilament Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000002751 oligonucleotide probe Substances 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 230000008816 organ damage Effects 0.000 description 1
- 230000005305 organ development Effects 0.000 description 1
- 230000021368 organ growth Effects 0.000 description 1
- 230000033667 organ regeneration Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 210000003460 periosteum Anatomy 0.000 description 1
- 210000001322 periplasm Anatomy 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 230000004983 pleiotropic effect Effects 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 238000007639 printing Methods 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 238000012514 protein characterization Methods 0.000 description 1
- 230000004850 protein–protein interaction Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000009256 replacement therapy Methods 0.000 description 1
- 230000002629 repopulating effect Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 238000012868 site-directed mutagenesis technique Methods 0.000 description 1
- 231100001055 skeletal defect Toxicity 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 239000003104 tissue culture media Substances 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
- 210000000143 trophectoderm cell Anatomy 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 210000004340 zona pellucida Anatomy 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
-
- 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
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/1833—Hepatocyte growth factor; Scatter factor; Tumor cytotoxic factor II
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/20—Interleukins [IL]
- A61K38/204—IL-6
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0647—Haematopoietic stem cells; Uncommitted or multipotent progenitors
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/10—Growth factors
- C12N2501/12—Hepatocyte growth factor [HGF]
-
- 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
- C12N2501/125—Stem cell factor [SCF], c-kit ligand [KL]
-
- 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
- C12N2501/20—Cytokines; Chemokines
- C12N2501/23—Interleukins [IL]
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Immunology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Organic Chemistry (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Developmental Biology & Embryology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Virology (AREA)
- Diabetes (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
Description
(b)該幹細胞を、HGFまたはそれの活性部分にさらすこと、および
(c)所定の閾値より上のCXCR4レベルを示す幹細胞を単離して、それにより、移植に適した幹細胞を産生させることを包含するものである、移植に適した幹細胞を産生させる方法が提供される。
アミノ酸 同義のグループ
Ser Ser、Thr、Gly、Asn
Arg Arg、Gln、Lys、Glu、His
Leu Ile、Phe、Tyr、Met、Val、Leu
Pro Gly、Ala、Thr、Pro
Thr Pro、Ser、Ala、Gly、His、Gln、Thr
Ala Gly、Thr、Pro、Ala
Val Met、Tyr、Phe、Ile、Leu、Val
Gly Ala、Thr、Pro、Ser、Gly
Ile Met、Tyr、Phe、Val、Leu、Ile
Phe Trp、Met、Tyr、Ile、Val、Leu、Phe
Tyr Trp、Met、Phe、Ile、Val、Leu、Tyr
Cys Ser、Thr、Cys
His Glu、Lys、Gln、Thr、Arg、His
Gln Glu、Lys、Asn、His、Thr、Arg、Gln
Asn Gln、Asp、Ser、Asn
Lys Glu、Gln、His、Arg、Lys
Asp Glu、Asn、Asp
Glu Asp、Lys、Asn、Gln、His、Arg、Glu
Met Phe、Ile、Val、Leu、Met
Trp Trp
アミノ酸 同義のグループ
Sers Sers
Arc His、Lys、Arg
Leu Ile、Phe、Met、Leu
Pro Ala、Pro
Thr Thr
Ala Pro、Ala
Val Met、Ile、Val
Gly Gly
Ilea Ile、Met、Phe、Val、Leu
Phe Met、Tyr、Ile、Leu、Phe
Try Phi、Try
Cys Ser、Cys
His Arg、Gln、His
Gln Glu、His、Gln
Asn Asp、Asn
Lys Arg、Lys
Asp Asn、Asp
Glu FLN、Glu
Met Phe、Ile、Val、Leu、Met
Trp Trp
アミノ酸 同義のグループ
Sers Sers
Arc Arc
Leu Ile、Met、Leu
Pro Pro
Thr Thar
Alan Alan
Val Val
Gly Gly
Ilea Ile、Met、Leu
Phi Phi
Try Try
Cys Ser、Cys
His His
Gln Gln
Asn Asn
Lys Lys
Asp Asp
Glu Glu
Met Ile、Leu、Met
Trp Trp
用語「「ストリンジェントな条件」は、ハイブリダイゼーションおよびそれにひきつづく洗浄(washing)の条件に該当し、それを当業者では、従来「ストリンジェント」と呼ばれる。Ausubelら、Current Protocols in Molecular Biology、グリーン・パブリケーションズ・アンド・ウイリー・インターサイエンス、ニューヨーク州ニューヨーク、1987-1995;Sambrookら、Molecular Cloning:A Laboratory Manual、コールド・スプリング・ハーバー・ラボラトリー、ニューヨーク州コールド・スプリング・ハーバー、1989年を参照。
Tm=81.5C+16.6(LogM)+0.41(%GC)−0.61(%from)−500/L
HGFを介した運動性およびCXCR4が増大されることは、損傷を受けた肝臓へのヒトCD34+前駆細胞の遊走を仲介する。
臍帯血のCD34+濃縮細胞を、サイトカインの非存在下、またはCXCR4発現およびSDF−1依存性遊走[Peled(1999年)Science 283巻:845−848頁]を誘導することが知られている、幹細胞因子、HGFまたは両方のサイトカインの組合せの存在下において、40時間培養した。その後細胞を、抗CXCR4および/または抗重合化アクチンとインキュベートし、PBSで頻繁に洗浄し、そしてファロイジン−TRITCおよびヤギ抗ウサギAlexa488とインキュベートした。サイトカインの非存在で培養されたCD34+細胞は、丸い形態を維持する一方で、SCFで培養した細胞は広がっており、そして分極していた。興味深くは、HGFは単独で、細胞表面からアクチンをベースとする突起部の形成を誘導し、そしてSCFとHGFの組合せは、SCFまたはHGF単独で観察されるもの(データは示されず)と異なる表現型であるラメリポジウム形成(lamellipodia formation)を促進した。最も重要なことに、これらの細胞骨格再編成は、CXCR4アップレギュレーション(図1A)およびSDF−1に対し機能的に増強された走化性応答(図1B)と関連があった。HGFは、ヒト前駆体単独の走化性を誘導しなかった(データは示されず)。しかし、HGFは、ヒト前駆体の運動性を増大させ、そしてSCFと相乗作用して、CXCR4発現およびSDF−1で誘導される方向性遊走(directional migration)の両方を可能とした。
照射は、肝臓および骨髄でのHGFをアップレギュレートする
移植前に使用され、そしてSDF−1のような様々なサイトカインをアップレギュレートすることが知られている照射が、肝臓そして骨髄でのHGFのアップレギュレーションを誘導しうるかを探索した。
HGFはSCFと相乗作用して、臍帯血のCD34+細胞の再構築能力を増大させる。
HGFは、CCl4損傷に続いて、SDF−1に向かって遊走する骨髄細胞の能力、および前駆細胞可動化の速度を増大させる。
Claims (74)
- 化学誘引物質に対する幹細胞の感受性を増大させる方法であって、幹細胞の少なくとも1種の化学誘引物質受容体のレベルを増大させて、それにより化学誘引物質に対する幹細胞の感受性を増大させる能力があるHGFまたはそれの活性部分に、幹細胞をさらすことを包含する方法。
- 前記少なくとも1種の化学誘引物質受容体が、CXCR4である請求項1記載の方法。
- さらに、幹細胞を、成長因子および/またはサイトカインにさらすことを包含する請求項1記載の方法。
- 前記成長因子および/またはサイトカインが、SCFおよびIL−6よりなる群から選択される請求項3記載の方法。
- 幹細胞が、造血幹細胞である請求項1記載の方法。
- 前記造血幹細胞が、CD34+造血幹細胞である請求項5記載の方法。
- 前記造血幹細胞が、CD34+/CD38-/低造血幹細胞である請求項6記載の方法。
- 造血幹細胞が、間葉幹細胞である請求項1記載の方法。
- 前記HGFまたはそれの前記活性部分に幹細胞をさらすことは、
(i)幹細胞中で該HGFまたはそれの該活性部分をコードするポリヌクレオチドを発現させ;および/または
(ii)その幹細胞を、該HGFまたはそれの該活性部分と接触させることによって達成される請求項1記載の方法。 - さらに、幹細胞をHGF−受容体にさらすことを包含する請求項1記載の方法。
- 細胞または組織交換を必要とする障害を治療する方法であって、それを必要とする対象に、前記幹細胞の少なくとも1種の化学誘引物質受容体のレベルを増大させて、それによりその対象における細胞または組織交換を必要とする障害を治療する能力があるHGFまたはそれの活性部分で処理した治療上有効な量の幹細胞を供することを包含する方法。
- 前記少なくとも1種の化学誘引物質受容体が、CXCR4である請求項11記載の方法。
- さらに、幹細胞の前記少なくとも1種の化学誘引物質受容体の該レベルを増大させる能力がある、成長因子および/またはサイトカインで、前記幹細胞を処置することを包含する請求項11記載の方法。
- 前記成長因子および/またはサイトカインが、SCFおよびIL−6よりなる群から選択される請求項13記載の方法。
- 前記幹細胞が、造血幹細胞である請求項11記載の方法。
- 前記造血幹細胞が、CD34+造血幹細胞である請求項15記載の方法。
- 前記造血幹細胞が、CD34+/CD38-/低造血幹細胞である請求項16記載の方法。
- 前記幹細胞が、間葉幹細胞である請求項11記載の方法。
- 細胞または組織交換を必要とする障害を治療する方法であって、それを必要とする対象に、幹細胞の少なくとも1種の化学誘引物質受容体のレベルを増大させ、それにより細胞または組織交換を必要とする障害を治療する能力があるHGFまたはそれの活性部分の治療上有効な量を供することを包含する方法。
- 前記少なくとも1つの化学誘引物質受容体が、CXCR4である請求項19記載の方法。
- さらに、幹細胞の前記少なくとも1種の化学誘引物質受容体の該レベルを増大させる能力のある、成長因子および/またはサイトカインの治療上有効な量を、前記それを必要とする対象に供することを包含する請求項19記載の方法。
- 前記成長因子および/またはサイトカインが、SCFおよびIL−6よりなる群から選択される請求項21記載の方法。
- さらに、前記それを必要とする対象に、幹細胞を供することを包含する請求項19〜22のいずれかに記載の方法。
- 前記造血幹細胞が、CD34+造血幹細胞である請求項23記載の方法。
- 前記造血幹細胞が、CD34+/CD38-/低造血幹細胞である請求項24記載の方法。
- 前記幹細胞が、間葉幹細胞である請求項19記載の方法。
- 標的組織に対する幹細胞のホーミングを増大させるための医薬品の製造のためのHGFまたはそれの活性部分の用途。
- 前記幹細胞が、造血幹細胞である請求項27記載の用途。
- 前記造血幹細胞が、CD34+造血幹細胞である請求項28記載の用途。
- 前記造血幹細胞が、CD34+/CD38-/低造血幹細胞である請求項29記載の用途。
- 前記幹細胞が、間葉幹細胞である請求項27記載の用途。
- 前記標的組織が、骨髄、血管、心臓、肺、肝臓、膵臓、腎臓、神経系、皮膚、骨および骨格筋よりなる群から選択される請求項27記載の用途。
- さらに、成長因子および/またはサイトカインを包含する請求項27〜32のいずれかに記載の用途。
- 前記成長因子および/またはサイトカインは、SCFおよびIL−6より構成される群から選択される請求項33記載の用途。
- 該成長因子が、SCFである請求項34記載の用途。
- 移植に適した幹細胞を産生させる方法であって、
(a)幹細胞を採取すること、
(b)該幹細胞を、HGFまたはそれの活性部分にさらすこと、
(c)所定の閾値より上のCXCR4レベルを有する幹細胞を単離して、それにより、移植に適した幹細胞を産生させること、
を包含する方法。 - 前記幹細胞を採取することが、
(i)幹細胞可動化手段;および/または
(ii)外科的手段によって達成される請求項36記載の方法。 - さらに、CXCR4の発現を増大させる能力のある成長因子および/またはサイトカインに前記幹細胞をさらすことを包含する請求項36記載の方法。
- 前記成長因子および/またはサイトカインが、SCFおよびIL−6よりなる群から選択される請求項38記載の方法。
- 前記幹細胞が、造血幹細胞である請求項36記載の方法。
- 前記造血幹細胞が、CD34+造血幹細胞である請求項40記載の方法。
- 前記造血幹細胞が、CD34+/CD38-/低造血幹細胞である請求項41記載の方法。
- 前記造血幹細胞が、間葉幹細胞である請求項36記載の方法。
- 前記HGFまたはそれの該活性部分に前記幹細胞をさらすことが、
(i)該幹細胞中で該HGFまたはそれの活性部分をコードするポリヌクレオチドを発現させ;および/または
(ii)該幹細胞を、該HGFまたはそれの活性部分と接触させることによって達成される請求項36記載の方法。 - 前記所定の閾値より上のCXCR4レベルを有する幹細胞を単離することが、FACSによって達成される請求項36記載の方法。
- さらに、工程(c)に続いて前記所定の閾値より上のCXCR4レベルを有する前記幹細胞のホーミング能力を測定することを包含する請求項45記載の方法。
- HGFまたはそれの活性部分をコードする第一のポリヌクレオチド配列、および細胞中の該ポリヌクレオチドの発現を指示する誘導性シス作用調節因子、および前記第一のポリヌクレオチド配列に翻訳で融合されるべき第二のポリヌクレオチド配列を包含し、前記第二のポリヌクレオチド配列は、前記細胞の中から外へ前記HGFまたはそれの該活性部分の分泌を指示する能力のあるシグナルペプチドをコードするものである核酸構築物を包含する幹細胞。
- さらに、IL−6およびSCFよりなる群から選択されるサイトカインまたは成長因子をコードする第三のポリヌクレオチド配列を包含する請求項47記載の幹細胞。
- SCFである第三のポリヌクレオチドを包含する請求項48記載の幹細胞。
- 前記幹細胞が、造血幹細胞である請求項47〜49のいずれかに記載の幹細胞。
- HGFまたはそれの活性部分をコードする内因性ポリヌクレオチドを発現するように形質転換された幹細胞を包含する細胞株。
- 前記幹細胞が、造血幹細胞である請求項50または51記載の細胞株。
- 前記造血幹細胞が、CD34+造血幹細胞である請求項52記載の細胞株。
- 前記造血幹細胞が、CD34+/CD38-/低造血幹細胞である請求項53記載の細胞株。
- 前記幹細胞が、間葉幹細胞である請求項52記載の細胞株。
- 細胞培養物であって、
(i)幹細胞;および
(ii)前記幹細胞の少なくとも1種の化学誘引物質受容体のレベルを増大させる能力のあるHGFまたはそれの活性部分のそれぞれを発現するフィーダー細胞を包含する細胞培養物。 - 前記幹細胞が、造血幹細胞である請求項56記載の細胞培養物。
- 前記造血幹細胞が、CD34+造血幹細胞である請求項57記載の細胞培養物。
- 前記造血幹細胞が、CD34+/CD38-/低造血幹細胞である請求項58記載の細胞培養物。
- 前記幹細胞が、間葉幹細胞である請求項56記載の細胞培養物。
- 化学誘引物質に対する幹細胞の感受性を増大させる方法であって、
幹細胞の内因性HGFまたはそれの活性部分の発現または活性をアップレギュレートして、それにより化学誘引物質に対する幹細胞の感受性を増大させることを包含する方法。 - 幹細胞運動性を増大させる方法であって、幹細胞の運動性を増大させる能力があるHGFまたはそれの活性部分に、幹細胞をさらすことを包含する方法。
- さらに、成長因子および/またはサイトカインに幹細胞をさらすことを包含する請求項62記載の方法。
- 前記成長因子および/またはサイトカインが、SCFおよびIL−6よりなる群から選択される請求項63記載の方法。
- サイトカインが、SCFである請求項64記載の方法。
- 前記幹細胞が、造血幹細胞である請求項62記載の方法。
- 前記造血幹細胞が、CD34+造血幹細胞である請求項66記載の方法。
- 前記造血幹細胞が、CD34+/CD38-/低造血幹細胞である請求項67記載の方法。
- 幹細胞が、間葉幹細胞である請求項62記載の方法。
- 前記HGFまたはそれの該活性部分に幹細胞をさらすことが、
(i)幹細胞中の該HGFまたはそれの該活性部分をコードするポリヌクレオチドを発現させ;および/または
(ii)該HGFまたはそれの該活性部分と、幹細胞を接触させることによって達成される請求項62記載の方法。 - 臓器炎症および/または損傷に罹っている対象における損傷臓器に対する自家再増殖および/または自家移植を促進する方法であって、幹細胞の運動性を増大させる能力があるHGFまたはそれの活性部分の投与を包含する方法。
- さらに、SCFを包含する、請求項71記載の自家再増殖および/または自家移植を促進する方法。
- 幹細胞およびSCFの運動性を増大させる能力があるHGFまたはそれの活性部分を包含する医薬組成物。
- 細胞または組織交換を必要とする障害を治療するための請求項73記載の医薬組成物。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IL15530303A IL155303A0 (en) | 2003-04-08 | 2003-04-08 | Stem cells having increased sensitivity to a chemoattractant and methods of generating and using same |
IL155303 | 2003-04-08 | ||
IL15930703A IL159307A0 (en) | 2003-12-10 | 2003-12-10 | Stem cells having increased sensitivity to a chemo-attractant and methods of generating and using same |
IL159307 | 2003-12-10 | ||
PCT/IL2004/000315 WO2004090121A2 (en) | 2003-04-08 | 2004-04-07 | Stem cells having increased sensitivity to a chemoattractant and methods of generating and using same |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2010158300A Division JP5362659B2 (ja) | 2003-04-08 | 2010-07-12 | 化学誘引物質に対する増大させた感受性を有する幹細胞およびそれを産生および使用する方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2006522604A true JP2006522604A (ja) | 2006-10-05 |
JP4865541B2 JP4865541B2 (ja) | 2012-02-01 |
Family
ID=33161264
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2006507603A Expired - Fee Related JP4865541B2 (ja) | 2003-04-08 | 2004-04-07 | 化学誘引物質に対する増大させた感受性を有する幹細胞およびそれを産生および使用する方法 |
JP2010158300A Expired - Fee Related JP5362659B2 (ja) | 2003-04-08 | 2010-07-12 | 化学誘引物質に対する増大させた感受性を有する幹細胞およびそれを産生および使用する方法 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2010158300A Expired - Fee Related JP5362659B2 (ja) | 2003-04-08 | 2010-07-12 | 化学誘引物質に対する増大させた感受性を有する幹細胞およびそれを産生および使用する方法 |
Country Status (8)
Country | Link |
---|---|
US (1) | US8029780B2 (ja) |
EP (1) | EP1613742A2 (ja) |
JP (2) | JP4865541B2 (ja) |
AU (1) | AU2004227205B2 (ja) |
CA (1) | CA2519975C (ja) |
IL (2) | IL171254A (ja) |
NO (1) | NO20055227L (ja) |
WO (1) | WO2004090121A2 (ja) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101495623B (zh) | 2006-03-24 | 2013-09-11 | 儿童医疗中心有限公司 | 调节造血干细胞生长的方法 |
US9402852B2 (en) | 2006-10-20 | 2016-08-02 | Children's Medical Center Corporation | Method to enhance tissue regeneration |
WO2008073748A1 (en) | 2006-12-08 | 2008-06-19 | University Of Rochester | Expansion of hematopoietic stem cells |
US20110165128A1 (en) * | 2008-03-07 | 2011-07-07 | Columbia University In The City Of New York | Homing in mesenchymal stem cells |
CN102245758A (zh) | 2008-11-06 | 2011-11-16 | 印第安纳大学研究与技术公司 | 增强造血干细胞植入过程的材料和方法 |
SG10201602423TA (en) | 2011-09-30 | 2016-05-30 | Bluebird Bio Inc | Compounds For Improved Viral Transduction |
JP6220791B2 (ja) | 2011-12-02 | 2017-10-25 | フェイト セラピューティクス,インコーポレイテッド | 増強された幹細胞組成物 |
US10162168B2 (en) | 2013-05-03 | 2018-12-25 | Wilcox Industries Corp. | Binocular bridge for thermal viewing device |
WO2017139561A1 (en) | 2016-02-12 | 2017-08-17 | Bluebird Bio, Inc. | Vcn enhancer compositions and methods of using the same |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1993003061A1 (en) * | 1991-07-26 | 1993-02-18 | Toray Industries, Incorporated | Hematopoietic stem cell multiplier |
WO1997007824A1 (fr) * | 1995-08-29 | 1997-03-06 | Sumitomo Pharmaceuticals Co., Ltd. | Medicament comprenant le gene hgf |
JPH10509951A (ja) * | 1994-11-24 | 1998-09-29 | ドンペ・ソチエタ・ペル・アチオニ | 造血細胞の増殖および分化を誘導するための肝細胞増殖因子の使用 |
JPH11127859A (ja) * | 1997-10-28 | 1999-05-18 | Kirin Brewery Co Ltd | 造血幹細胞の分化・増殖調節方法 |
JP2001517427A (ja) * | 1997-09-25 | 2001-10-09 | グリコテック コーポレイション | 造血幹細胞を結合するための方法および組成物 |
WO2002050263A2 (en) * | 2000-12-21 | 2002-06-27 | Imperial College Innovations Limited | Methods_for treating tissue damage by bone-marrow derived stem cells |
JP2002535981A (ja) * | 1999-02-04 | 2002-10-29 | テクニオン リサーチ アンド デブェロップメント ファウンデーション リミテド | 造血幹細胞および/または前駆細胞を維持および増加するための方法および装置 |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5622853A (en) * | 1990-05-01 | 1997-04-22 | Becton Dickinson And Company | T lymphocyte precursor |
DE4422667A1 (de) * | 1994-06-30 | 1996-01-04 | Boehringer Ingelheim Int | Verfahren zur Herstellung und Züchtung hämatopoetischer Vorläuferzellen |
JPH10295369A (ja) * | 1997-02-26 | 1998-11-10 | Japan Tobacco Inc | 造血幹細胞の製造方法 |
US6586192B1 (en) * | 1998-05-29 | 2003-07-01 | Thomas Jefferson University | Compositions and methods for use in affecting hematopoietic stem cell populations in mammals |
IL125532A0 (en) * | 1998-07-27 | 1999-03-12 | Yeda Res & Dev | Hematopoietic cell composition for use in transplantation |
US6642049B1 (en) * | 1998-12-04 | 2003-11-04 | The United States Of America As Represented By The Secretary Of The Navy | Human brain endothelial cells and growth medium and method for expansion of primitive CD34+CD38-bone marrow stem cells |
AU2001280149A1 (en) * | 2000-08-25 | 2002-03-04 | Asahi Kasei Kabushiki Kaisha | Stem cell culture medium and culture method by using the same |
CA2442177A1 (en) * | 2001-03-29 | 2002-10-10 | Ixion Biotechnology, Inc. | Method for transdifferentiation of non-pancreatic stem cells to the pancreatic differentiation pathway |
EP2322618A1 (en) * | 2001-07-10 | 2011-05-18 | Johnson & Johnson Research Pty Limited | Methods for genetic modification of hematopoietic progenitor cells and uses of the modified cells |
-
2004
- 2004-04-07 CA CA2519975A patent/CA2519975C/en not_active Expired - Fee Related
- 2004-04-07 US US10/552,331 patent/US8029780B2/en not_active Expired - Fee Related
- 2004-04-07 AU AU2004227205A patent/AU2004227205B2/en not_active Ceased
- 2004-04-07 EP EP04726247A patent/EP1613742A2/en not_active Withdrawn
- 2004-04-07 WO PCT/IL2004/000315 patent/WO2004090121A2/en active Application Filing
- 2004-04-07 JP JP2006507603A patent/JP4865541B2/ja not_active Expired - Fee Related
-
2005
- 2005-10-02 IL IL171254A patent/IL171254A/en not_active IP Right Cessation
- 2005-11-07 NO NO20055227A patent/NO20055227L/no unknown
-
2009
- 2009-08-03 IL IL200207A patent/IL200207A/en not_active IP Right Cessation
-
2010
- 2010-07-12 JP JP2010158300A patent/JP5362659B2/ja not_active Expired - Fee Related
Patent Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1993003061A1 (en) * | 1991-07-26 | 1993-02-18 | Toray Industries, Incorporated | Hematopoietic stem cell multiplier |
EP0550769A1 (en) * | 1991-07-26 | 1993-07-14 | Toray Industries, Inc. | Hematopoietic stem cell multiplier |
JP3395181B2 (ja) * | 1991-07-26 | 2003-04-07 | 東レ株式会社 | 造血幹細胞増加剤 |
JPH10509951A (ja) * | 1994-11-24 | 1998-09-29 | ドンペ・ソチエタ・ペル・アチオニ | 造血細胞の増殖および分化を誘導するための肝細胞増殖因子の使用 |
US5968501A (en) * | 1994-11-24 | 1999-10-19 | Dompe S.P.A. | Hepatocyte growth factor--induced proliferation and differentiation of erythroid cells |
WO1997007824A1 (fr) * | 1995-08-29 | 1997-03-06 | Sumitomo Pharmaceuticals Co., Ltd. | Medicament comprenant le gene hgf |
JP2001517427A (ja) * | 1997-09-25 | 2001-10-09 | グリコテック コーポレイション | 造血幹細胞を結合するための方法および組成物 |
JPH11127859A (ja) * | 1997-10-28 | 1999-05-18 | Kirin Brewery Co Ltd | 造血幹細胞の分化・増殖調節方法 |
JP2002535981A (ja) * | 1999-02-04 | 2002-10-29 | テクニオン リサーチ アンド デブェロップメント ファウンデーション リミテド | 造血幹細胞および/または前駆細胞を維持および増加するための方法および装置 |
WO2002050263A2 (en) * | 2000-12-21 | 2002-06-27 | Imperial College Innovations Limited | Methods_for treating tissue damage by bone-marrow derived stem cells |
Non-Patent Citations (3)
Title |
---|
BLOOD, vol. 85, JPN6009054267, 1995, pages 3093 - 3100, ISSN: 0002039968 * |
BLOOD, vol. 91, no. 12, JPN6011023981, 1988, pages 4523 - 4530, ISSN: 0001915719 * |
EXP. HEMATOL., vol. 26, JPN6009054263, 1998, pages 885 - 894, ISSN: 0002039967 * |
Also Published As
Publication number | Publication date |
---|---|
IL200207A (en) | 2012-06-28 |
WO2004090121A3 (en) | 2004-12-29 |
US8029780B2 (en) | 2011-10-04 |
IL200207A0 (en) | 2011-08-01 |
NO20055227L (no) | 2005-11-07 |
US20070172464A1 (en) | 2007-07-26 |
EP1613742A2 (en) | 2006-01-11 |
CA2519975C (en) | 2013-07-02 |
IL171254A (en) | 2013-06-27 |
WO2004090121A2 (en) | 2004-10-21 |
JP5362659B2 (ja) | 2013-12-11 |
AU2004227205A1 (en) | 2004-10-21 |
JP4865541B2 (ja) | 2012-02-01 |
JP2010263907A (ja) | 2010-11-25 |
IL171254A0 (en) | 2011-08-01 |
CA2519975A1 (en) | 2004-10-21 |
AU2004227205B2 (en) | 2010-06-10 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5362659B2 (ja) | 化学誘引物質に対する増大させた感受性を有する幹細胞およびそれを産生および使用する方法 | |
US8367057B2 (en) | Stem cells suitable for transplantation, their preparation and pharmaceutical compositions comprising them | |
US20080193426A1 (en) | Migration of hematopoietic stem cells and progenitor cells to the liver | |
Peters et al. | Interleukin-6 and the soluble interleukin-6 receptor induce stem cell factor and Flt-3L expression in vivo and in vitro | |
JP4865540B2 (ja) | 化学誘引物質に対する増大された感受性を有する幹細胞およびそれを産生および使用する方法 | |
JP2009159868A (ja) | 造血幹細胞の維持・増幅方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20070327 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20091020 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20100118 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20100125 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100319 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20100413 |
|
RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20100524 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20100524 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100712 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110517 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20110812 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20110819 |
|
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: 20111011 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20111110 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20141118 Year of fee payment: 3 |
|
R150 | Certificate of patent or registration of utility model |
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 |
|
LAPS | Cancellation because of no payment of annual fees |