JP2022024047A - 線維芽細胞治療活性を増強する方法 - Google Patents
線維芽細胞治療活性を増強する方法 Download PDFInfo
- Publication number
- JP2022024047A JP2022024047A JP2021184431A JP2021184431A JP2022024047A JP 2022024047 A JP2022024047 A JP 2022024047A JP 2021184431 A JP2021184431 A JP 2021184431A JP 2021184431 A JP2021184431 A JP 2021184431A JP 2022024047 A JP2022024047 A JP 2022024047A
- Authority
- JP
- Japan
- Prior art keywords
- cells
- fibroblasts
- cell
- platelet
- disc
- 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
- 210000002950 fibroblast Anatomy 0.000 title abstract description 111
- 238000000034 method Methods 0.000 title abstract description 58
- 230000001225 therapeutic effect Effects 0.000 title abstract description 10
- 230000002708 enhancing effect Effects 0.000 title description 2
- 210000004027 cell Anatomy 0.000 abstract description 224
- 210000004623 platelet-rich plasma Anatomy 0.000 abstract description 62
- 239000000203 mixture Substances 0.000 abstract description 32
- 108090000623 proteins and genes Proteins 0.000 abstract description 24
- 239000003102 growth factor Substances 0.000 abstract description 22
- 102000004127 Cytokines Human genes 0.000 abstract description 14
- 108090000695 Cytokines Proteins 0.000 abstract description 14
- 206010021143 Hypoxia Diseases 0.000 abstract description 9
- 102000004169 proteins and genes Human genes 0.000 abstract description 9
- 238000000338 in vitro Methods 0.000 abstract description 8
- 230000001146 hypoxic effect Effects 0.000 abstract description 5
- 238000003556 assay Methods 0.000 abstract description 3
- 102000004196 processed proteins & peptides Human genes 0.000 abstract description 3
- 108090000765 processed proteins & peptides Proteins 0.000 abstract description 3
- 230000003416 augmentation Effects 0.000 abstract description 2
- 230000016396 cytokine production Effects 0.000 abstract 1
- 230000037314 wound repair Effects 0.000 abstract 1
- 239000002609 medium Substances 0.000 description 33
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 26
- 239000013598 vector Substances 0.000 description 26
- 239000001963 growth medium Substances 0.000 description 25
- 208000008035 Back Pain Diseases 0.000 description 21
- 206010061246 Intervertebral disc degeneration Diseases 0.000 description 20
- 230000001965 increasing effect Effects 0.000 description 19
- 230000014509 gene expression Effects 0.000 description 18
- 238000011282 treatment Methods 0.000 description 18
- 239000011159 matrix material Substances 0.000 description 16
- 210000001519 tissue Anatomy 0.000 description 16
- 230000015572 biosynthetic process Effects 0.000 description 15
- 210000001185 bone marrow Anatomy 0.000 description 15
- 230000000694 effects Effects 0.000 description 15
- 239000010410 layer Substances 0.000 description 15
- 208000008930 Low Back Pain Diseases 0.000 description 14
- 108010067787 Proteoglycans Proteins 0.000 description 14
- 102000016611 Proteoglycans Human genes 0.000 description 14
- 210000004369 blood Anatomy 0.000 description 14
- 239000008280 blood Substances 0.000 description 14
- 238000003306 harvesting Methods 0.000 description 13
- 238000004519 manufacturing process Methods 0.000 description 13
- 230000035755 proliferation Effects 0.000 description 12
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 11
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 11
- 230000003110 anti-inflammatory effect Effects 0.000 description 11
- 229940126864 fibroblast growth factor Drugs 0.000 description 11
- 230000006870 function Effects 0.000 description 11
- 210000002381 plasma Anatomy 0.000 description 11
- 230000008569 process Effects 0.000 description 11
- 238000011069 regeneration method Methods 0.000 description 11
- 230000008929 regeneration Effects 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- -1 Hyaluronic acid benzyl ester Chemical class 0.000 description 9
- 230000002491 angiogenic effect Effects 0.000 description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 9
- 238000001574 biopsy Methods 0.000 description 9
- 239000001301 oxygen Substances 0.000 description 9
- 229910052760 oxygen Inorganic materials 0.000 description 9
- 239000000523 sample Substances 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 8
- 230000000735 allogeneic effect Effects 0.000 description 8
- 210000001612 chondrocyte Anatomy 0.000 description 8
- 229920002674 hyaluronan Polymers 0.000 description 8
- 229960003160 hyaluronic acid Drugs 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 238000001890 transfection Methods 0.000 description 8
- 206010061218 Inflammation Diseases 0.000 description 7
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 7
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 7
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 7
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 7
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 7
- 230000004663 cell proliferation Effects 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 230000004054 inflammatory process Effects 0.000 description 7
- 210000002510 keratinocyte Anatomy 0.000 description 7
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 6
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 6
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 6
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 6
- 102000000589 Interleukin-1 Human genes 0.000 description 6
- 108010002352 Interleukin-1 Proteins 0.000 description 6
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 6
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 6
- 108010009583 Transforming Growth Factors Proteins 0.000 description 6
- 102000009618 Transforming Growth Factors Human genes 0.000 description 6
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 6
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 230000000975 bioactive effect Effects 0.000 description 6
- 238000005119 centrifugation Methods 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 238000005138 cryopreservation Methods 0.000 description 6
- 238000012258 culturing Methods 0.000 description 6
- 239000000975 dye Substances 0.000 description 6
- 239000012091 fetal bovine serum Substances 0.000 description 6
- 230000012010 growth Effects 0.000 description 6
- 239000000017 hydrogel Substances 0.000 description 6
- 230000006698 induction Effects 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000003550 marker Substances 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 210000005259 peripheral blood Anatomy 0.000 description 6
- 239000011886 peripheral blood Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 230000001172 regenerating effect Effects 0.000 description 6
- 210000003491 skin Anatomy 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 230000004936 stimulating effect Effects 0.000 description 6
- 230000035899 viability Effects 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 5
- 108010074328 Interferon-gamma Proteins 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 208000002193 Pain Diseases 0.000 description 5
- 210000001744 T-lymphocyte Anatomy 0.000 description 5
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 5
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 5
- 230000033115 angiogenesis Effects 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 230000002757 inflammatory effect Effects 0.000 description 5
- 239000006166 lysate Substances 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 239000002953 phosphate buffered saline Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- 210000000130 stem cell Anatomy 0.000 description 5
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 5
- 230000003827 upregulation Effects 0.000 description 5
- 108010022452 Collagen Type I Proteins 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 101000800116 Homo sapiens Thy-1 membrane glycoprotein Proteins 0.000 description 4
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 4
- 102100030703 Interleukin-22 Human genes 0.000 description 4
- 239000004743 Polypropylene Substances 0.000 description 4
- 102100033523 Thy-1 membrane glycoprotein Human genes 0.000 description 4
- 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 4
- 102000040945 Transcription factor Human genes 0.000 description 4
- 108091023040 Transcription factor Proteins 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 210000004204 blood vessel Anatomy 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 230000010261 cell growth Effects 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 230000003412 degenerative effect Effects 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 230000029087 digestion Effects 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 230000007954 hypoxia Effects 0.000 description 4
- 210000002865 immune cell Anatomy 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 230000036961 partial effect Effects 0.000 description 4
- 102000040430 polynucleotide Human genes 0.000 description 4
- 108091033319 polynucleotide Proteins 0.000 description 4
- 239000002157 polynucleotide Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 230000017423 tissue regeneration Effects 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- 108010027612 Batroxobin Proteins 0.000 description 3
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 3
- 102000008186 Collagen Human genes 0.000 description 3
- 108010035532 Collagen Proteins 0.000 description 3
- 102000012422 Collagen Type I Human genes 0.000 description 3
- 108010041390 Collagen Type II Proteins 0.000 description 3
- 108060005980 Collagenase Proteins 0.000 description 3
- 102000029816 Collagenase Human genes 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 3
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 3
- 108010049003 Fibrinogen Proteins 0.000 description 3
- 102000008946 Fibrinogen Human genes 0.000 description 3
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 3
- 102000003971 Fibroblast Growth Factor 1 Human genes 0.000 description 3
- 108090000385 Fibroblast growth factor 7 Proteins 0.000 description 3
- 102000003972 Fibroblast growth factor 7 Human genes 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 102000008070 Interferon-gamma Human genes 0.000 description 3
- 108090000174 Interleukin-10 Proteins 0.000 description 3
- 102000003814 Interleukin-10 Human genes 0.000 description 3
- 108090000177 Interleukin-11 Proteins 0.000 description 3
- 102000003815 Interleukin-11 Human genes 0.000 description 3
- 108010065805 Interleukin-12 Proteins 0.000 description 3
- 108090000176 Interleukin-13 Proteins 0.000 description 3
- 108090000172 Interleukin-15 Proteins 0.000 description 3
- 102000003810 Interleukin-18 Human genes 0.000 description 3
- 108090000171 Interleukin-18 Proteins 0.000 description 3
- 108010002350 Interleukin-2 Proteins 0.000 description 3
- 108010065637 Interleukin-23 Proteins 0.000 description 3
- 108010066979 Interleukin-27 Proteins 0.000 description 3
- 108090000978 Interleukin-4 Proteins 0.000 description 3
- 108090001005 Interleukin-6 Proteins 0.000 description 3
- 108090001007 Interleukin-8 Proteins 0.000 description 3
- 108010002335 Interleukin-9 Proteins 0.000 description 3
- 102000003945 NF-kappa B Human genes 0.000 description 3
- 108010057466 NF-kappa B Proteins 0.000 description 3
- 102000004211 Platelet factor 4 Human genes 0.000 description 3
- 108090000778 Platelet factor 4 Proteins 0.000 description 3
- 206010037779 Radiculopathy Diseases 0.000 description 3
- 230000006044 T cell activation Effects 0.000 description 3
- 108060008245 Thrombospondin Proteins 0.000 description 3
- 102000002938 Thrombospondin Human genes 0.000 description 3
- 230000001464 adherent effect Effects 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 229960002210 batroxobin Drugs 0.000 description 3
- 239000012867 bioactive agent Substances 0.000 description 3
- 230000003833 cell viability Effects 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 229920001436 collagen Polymers 0.000 description 3
- 230000002338 cryopreservative effect Effects 0.000 description 3
- 230000001086 cytosolic effect Effects 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000004520 electroporation Methods 0.000 description 3
- 210000002889 endothelial cell Anatomy 0.000 description 3
- 230000008472 epithelial growth Effects 0.000 description 3
- 239000013604 expression vector Substances 0.000 description 3
- 229940012952 fibrinogen Drugs 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 210000003953 foreskin Anatomy 0.000 description 3
- 238000007710 freezing Methods 0.000 description 3
- 230000008014 freezing Effects 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 230000006801 homologous recombination Effects 0.000 description 3
- 238000002744 homologous recombination Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 229960003130 interferon gamma Drugs 0.000 description 3
- 108090000681 interleukin 20 Proteins 0.000 description 3
- 108010074108 interleukin-21 Proteins 0.000 description 3
- 238000013411 master cell bank Methods 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 3
- 238000003908 quality control method Methods 0.000 description 3
- 230000008439 repair process Effects 0.000 description 3
- 230000001177 retroviral effect Effects 0.000 description 3
- 238000005070 sampling Methods 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 241000701161 unidentified adenovirus Species 0.000 description 3
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 2
- 108010081589 Becaplermin Proteins 0.000 description 2
- 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 2
- 108010049931 Bone Morphogenetic Protein 2 Proteins 0.000 description 2
- 108010049870 Bone Morphogenetic Protein 7 Proteins 0.000 description 2
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 2
- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 2
- 102100024506 Bone morphogenetic protein 2 Human genes 0.000 description 2
- 102100022544 Bone morphogenetic protein 7 Human genes 0.000 description 2
- 102100025250 C-X-C motif chemokine 14 Human genes 0.000 description 2
- 102400000730 Canstatin Human genes 0.000 description 2
- 101800000626 Canstatin Proteins 0.000 description 2
- 102000000503 Collagen Type II Human genes 0.000 description 2
- 108010001463 Collagen Type XVIII Proteins 0.000 description 2
- 102000047200 Collagen Type XVIII Human genes 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 102400001047 Endostatin Human genes 0.000 description 2
- 108010079505 Endostatins Proteins 0.000 description 2
- 206010063560 Excessive granulation tissue Diseases 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 108010073385 Fibrin Proteins 0.000 description 2
- 102000009123 Fibrin Human genes 0.000 description 2
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 2
- 102100028072 Fibroblast growth factor 4 Human genes 0.000 description 2
- 108090000381 Fibroblast growth factor 4 Proteins 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 2
- 108010090254 Growth Differentiation Factor 5 Proteins 0.000 description 2
- 102100035379 Growth/differentiation factor 5 Human genes 0.000 description 2
- 101710154606 Hemagglutinin Proteins 0.000 description 2
- 102100032742 Histone-lysine N-methyltransferase SETD2 Human genes 0.000 description 2
- 101000858068 Homo sapiens C-X-C motif chemokine 14 Proteins 0.000 description 2
- 101000654725 Homo sapiens Histone-lysine N-methyltransferase SETD2 Proteins 0.000 description 2
- 101001046870 Homo sapiens Hypoxia-inducible factor 1-alpha Proteins 0.000 description 2
- 102100022875 Hypoxia-inducible factor 1-alpha Human genes 0.000 description 2
- 102000014429 Insulin-like growth factor Human genes 0.000 description 2
- 102100026720 Interferon beta Human genes 0.000 description 2
- 102100037850 Interferon gamma Human genes 0.000 description 2
- 102000004289 Interferon regulatory factor 1 Human genes 0.000 description 2
- 108090000890 Interferon regulatory factor 1 Proteins 0.000 description 2
- 108010047761 Interferon-alpha Proteins 0.000 description 2
- 102000006992 Interferon-alpha Human genes 0.000 description 2
- 108090000467 Interferon-beta Proteins 0.000 description 2
- 108050003558 Interleukin-17 Proteins 0.000 description 2
- 102000013691 Interleukin-17 Human genes 0.000 description 2
- 108090001090 Lectins Proteins 0.000 description 2
- 102000004856 Lectins Human genes 0.000 description 2
- 241000713666 Lentivirus Species 0.000 description 2
- 108010052014 Liberase Proteins 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 2
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 2
- 102100039364 Metalloproteinase inhibitor 1 Human genes 0.000 description 2
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 2
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 2
- 240000007019 Oxalis corniculata Species 0.000 description 2
- 208000031481 Pathologic Constriction Diseases 0.000 description 2
- 108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 description 2
- 102100039418 Plasminogen activator inhibitor 1 Human genes 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 101710176177 Protein A56 Proteins 0.000 description 2
- 241000508269 Psidium Species 0.000 description 2
- 108010044012 STAT1 Transcription Factor Proteins 0.000 description 2
- 108010019992 STAT4 Transcription Factor Proteins 0.000 description 2
- 102000005886 STAT4 Transcription Factor Human genes 0.000 description 2
- 108010029477 STAT5 Transcription Factor Proteins 0.000 description 2
- 102000001712 STAT5 Transcription Factor Human genes 0.000 description 2
- 102100029904 Signal transducer and activator of transcription 1-alpha/beta Human genes 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- 208000020307 Spinal disease Diseases 0.000 description 2
- 101150052863 THY1 gene Proteins 0.000 description 2
- 108010031374 Tissue Inhibitor of Metalloproteinase-1 Proteins 0.000 description 2
- 108700019146 Transgenes Proteins 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 239000002870 angiogenesis inducing agent Substances 0.000 description 2
- 230000003160 anti-catabolic effect Effects 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 210000001130 astrocyte Anatomy 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 238000010009 beating Methods 0.000 description 2
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 2
- 229920000249 biocompatible polymer Polymers 0.000 description 2
- 229940112869 bone morphogenetic protein Drugs 0.000 description 2
- 210000004413 cardiac myocyte Anatomy 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000002648 chondrogenic effect Effects 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 229960002424 collagenase Drugs 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 208000018180 degenerative disc disease Diseases 0.000 description 2
- 230000000593 degrading effect Effects 0.000 description 2
- 210000004207 dermis Anatomy 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000002500 effect on skin Effects 0.000 description 2
- 230000003511 endothelial effect Effects 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 210000002744 extracellular matrix Anatomy 0.000 description 2
- 230000001605 fetal effect Effects 0.000 description 2
- 229950003499 fibrin Drugs 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 210000001654 germ layer Anatomy 0.000 description 2
- 210000001126 granulation tissue Anatomy 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 239000000185 hemagglutinin Substances 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 229940099472 immunoglobulin a Drugs 0.000 description 2
- 229940027941 immunoglobulin g Drugs 0.000 description 2
- 230000001506 immunosuppresive effect Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 230000014828 interferon-gamma production Effects 0.000 description 2
- 208000021600 intervertebral disc degenerative disease Diseases 0.000 description 2
- 208000028867 ischemia Diseases 0.000 description 2
- 239000002523 lectin Substances 0.000 description 2
- 239000003226 mitogen Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- OHDXDNUPVVYWOV-UHFFFAOYSA-N n-methyl-1-(2-naphthalen-1-ylsulfanylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1SC1=CC=CC2=CC=CC=C12 OHDXDNUPVVYWOV-UHFFFAOYSA-N 0.000 description 2
- 238000010899 nucleation Methods 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 2
- 210000002826 placenta Anatomy 0.000 description 2
- 229920000570 polyether Polymers 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 108020003519 protein disulfide isomerase Proteins 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000008672 reprogramming Effects 0.000 description 2
- 230000020341 sensory perception of pain Effects 0.000 description 2
- 230000036262 stenosis Effects 0.000 description 2
- 208000037804 stenosis Diseases 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 229940104230 thymidine Drugs 0.000 description 2
- 230000008467 tissue growth Effects 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 230000002485 urinary effect Effects 0.000 description 2
- 235000013311 vegetables Nutrition 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- 239000001763 2-hydroxyethyl(trimethyl)azanium Substances 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 101710186708 Agglutinin Proteins 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 241000710929 Alphavirus Species 0.000 description 1
- 102100022987 Angiogenin Human genes 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- 102000004411 Antithrombin III Human genes 0.000 description 1
- 108090000935 Antithrombin III Proteins 0.000 description 1
- 239000012583 B-27 Supplement Substances 0.000 description 1
- 108010074708 B7-H1 Antigen Proteins 0.000 description 1
- 108090000145 Bacillolysin Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 102100028728 Bone morphogenetic protein 1 Human genes 0.000 description 1
- 108090000654 Bone morphogenetic protein 1 Proteins 0.000 description 1
- 102100032367 C-C motif chemokine 5 Human genes 0.000 description 1
- 101100205030 Caenorhabditis elegans hars-1 gene Proteins 0.000 description 1
- 101100297347 Caenorhabditis elegans pgl-3 gene 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
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 108090000566 Caspase-9 Proteins 0.000 description 1
- 102100026550 Caspase-9 Human genes 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 108010055166 Chemokine CCL5 Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 235000019743 Choline chloride Nutrition 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 102100025137 Early activation antigen CD69 Human genes 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 108010041308 Endothelial Growth Factors Proteins 0.000 description 1
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 102100031706 Fibroblast growth factor 1 Human genes 0.000 description 1
- 108090001047 Fibroblast growth factor 10 Proteins 0.000 description 1
- 102000004864 Fibroblast growth factor 10 Human genes 0.000 description 1
- 102100037362 Fibronectin Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 101710140958 Formimidoyltetrahydrofolate cyclodeaminase Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 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
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 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
- 206010019909 Hernia Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000762366 Homo sapiens Bone morphogenetic protein 2 Proteins 0.000 description 1
- 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 description 1
- 101000846416 Homo sapiens Fibroblast growth factor 1 Proteins 0.000 description 1
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
- 101000994365 Homo sapiens Integrin alpha-6 Proteins 0.000 description 1
- 101000959820 Homo sapiens Interferon alpha-1/13 Proteins 0.000 description 1
- 101000853002 Homo sapiens Interleukin-25 Proteins 0.000 description 1
- 101000853000 Homo sapiens Interleukin-26 Proteins 0.000 description 1
- 101001128431 Homo sapiens Myeloid-derived growth factor Proteins 0.000 description 1
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
- 101710146024 Horcolin Proteins 0.000 description 1
- 101150003028 Hprt1 gene Proteins 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 108091054729 IRF family Proteins 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 1
- 108090001117 Insulin-Like Growth Factor II Proteins 0.000 description 1
- 102000048143 Insulin-Like Growth Factor II Human genes 0.000 description 1
- 102100032816 Integrin alpha-6 Human genes 0.000 description 1
- 108010041100 Integrin alpha6 Proteins 0.000 description 1
- 102000000426 Integrin alpha6 Human genes 0.000 description 1
- 108010022238 Integrin beta4 Proteins 0.000 description 1
- 102000012334 Integrin beta4 Human genes 0.000 description 1
- 102000016854 Interferon Regulatory Factors Human genes 0.000 description 1
- 101800003050 Interleukin-16 Proteins 0.000 description 1
- 108050009288 Interleukin-19 Proteins 0.000 description 1
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 description 1
- 102000013264 Interleukin-23 Human genes 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 102100039064 Interleukin-3 Human genes 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 108010002586 Interleukin-7 Proteins 0.000 description 1
- 208000003618 Intervertebral Disc Displacement Diseases 0.000 description 1
- 101710189395 Lectin Proteins 0.000 description 1
- 108090000581 Leukemia inhibitory factor Proteins 0.000 description 1
- 102100032352 Leukemia inhibitory factor Human genes 0.000 description 1
- 229940124761 MMP inhibitor Drugs 0.000 description 1
- 101710179758 Mannose-specific lectin Proteins 0.000 description 1
- 101710150763 Mannose-specific lectin 1 Proteins 0.000 description 1
- 101710150745 Mannose-specific lectin 2 Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- 102100031789 Myeloid-derived growth factor Human genes 0.000 description 1
- 206010028570 Myelopathy Diseases 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 206010029174 Nerve compression Diseases 0.000 description 1
- 208000031264 Nerve root compression Diseases 0.000 description 1
- 102000035092 Neutral proteases Human genes 0.000 description 1
- 108091005507 Neutral proteases Proteins 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 108010077077 Osteonectin Proteins 0.000 description 1
- 102000009890 Osteonectin Human genes 0.000 description 1
- 108010067372 Pancreatic elastase Proteins 0.000 description 1
- 102000016387 Pancreatic elastase Human genes 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000004721 Polyphenylene oxide Substances 0.000 description 1
- 229920011250 Polypropylene Block Copolymer Polymers 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 1
- 108010025832 RANK Ligand Proteins 0.000 description 1
- 238000011579 SCID mouse model Methods 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 208000008765 Sciatica Diseases 0.000 description 1
- 102100020814 Sequestosome-1 Human genes 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- 102000013275 Somatomedins Human genes 0.000 description 1
- 208000007103 Spondylolisthesis Diseases 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
- 102000043168 TGF-beta family Human genes 0.000 description 1
- 108091085018 TGF-beta family Proteins 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- 102000002689 Toll-like receptor Human genes 0.000 description 1
- 108020000411 Toll-like receptor Proteins 0.000 description 1
- 102000000887 Transcription factor STAT Human genes 0.000 description 1
- 108050007918 Transcription factor STAT Proteins 0.000 description 1
- 102000046299 Transforming Growth Factor beta1 Human genes 0.000 description 1
- 101800002279 Transforming growth factor beta-1 Proteins 0.000 description 1
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 102100024568 Tumor necrosis factor ligand superfamily member 11 Human genes 0.000 description 1
- 101710187743 Tumor necrosis factor receptor superfamily member 1A Proteins 0.000 description 1
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 108010031318 Vitronectin Proteins 0.000 description 1
- 102100035140 Vitronectin Human genes 0.000 description 1
- 108010046516 Wheat Germ Agglutinins Proteins 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000910 agglutinin Substances 0.000 description 1
- 229940050528 albumin Drugs 0.000 description 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
- 230000001195 anabolic effect Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 108010072788 angiogenin Proteins 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 229960005348 antithrombin iii Drugs 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 238000011882 arthroplasty Methods 0.000 description 1
- 230000003305 autocrine Effects 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 125000004181 carboxyalkyl group Chemical group 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 239000002771 cell marker Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 229960003178 choline chloride Drugs 0.000 description 1
- SGMZJAMFUVOLNK-UHFFFAOYSA-M choline chloride Chemical compound [Cl-].C[N+](C)(C)CCO SGMZJAMFUVOLNK-UHFFFAOYSA-M 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000003501 co-culture Methods 0.000 description 1
- 230000004186 co-expression Effects 0.000 description 1
- 238000012761 co-transfection Methods 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- 108091007734 digestive enzymes Proteins 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 210000000222 eosinocyte Anatomy 0.000 description 1
- 210000002514 epidermal stem cell Anatomy 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 210000004700 fetal blood Anatomy 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 210000000968 fibrocartilage Anatomy 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 239000012595 freezing medium Substances 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 210000004475 gamma-delta t lymphocyte Anatomy 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 102000045896 human BMP2 Human genes 0.000 description 1
- 229920013821 hydroxy alkyl cellulose Polymers 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 229960001438 immunostimulant agent Drugs 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 108010074109 interleukin-22 Proteins 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 210000005061 intracellular organelle Anatomy 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 229920006008 lipopolysaccharide Polymers 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 108010082117 matrigel Proteins 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 238000007799 mixed lymphocyte reaction assay Methods 0.000 description 1
- 239000003147 molecular marker Substances 0.000 description 1
- 238000009126 molecular therapy Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 230000001002 morphogenetic effect Effects 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 210000000581 natural killer T-cell Anatomy 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 210000001640 nerve ending Anatomy 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 230000037081 physical activity Effects 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000004094 preconcentration Methods 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000010909 process residue Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000011555 rabbit model Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000008458 response to injury Effects 0.000 description 1
- 229930002330 retinoic acid Natural products 0.000 description 1
- 230000000250 revascularization Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- HEBKCHPVOIAQTA-ZXFHETKHSA-N ribitol Chemical compound OC[C@H](O)[C@H](O)[C@H](O)CO HEBKCHPVOIAQTA-ZXFHETKHSA-N 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 208000013363 skeletal muscle disease Diseases 0.000 description 1
- 238000007390 skin biopsy Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000010414 supernatant solution Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000004114 suspension culture Methods 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 239000003634 thrombocyte concentrate Substances 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- 230000009772 tissue formation Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 108091007466 transmembrane glycoproteins Proteins 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 210000003954 umbilical cord Anatomy 0.000 description 1
- 210000003606 umbilical vein Anatomy 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
- C12N5/0656—Adult fibroblasts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- 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
-
- 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
- A61K35/33—Fibroblasts
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/10—Growth factors
- C12N2501/113—Acidic fibroblast growth factor (aFGF, FGF-1)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/10—Growth factors
- C12N2501/115—Basic fibroblast growth factor (bFGF, FGF-2)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/10—Growth factors
- C12N2501/15—Transforming growth factor beta (TGF-β)
-
- 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
- C12N2502/11—Coculture with; Conditioned medium produced by blood or immune system cells
- C12N2502/115—Platelets, megakaryocytes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0696—Artificially induced pluripotent stem cells, e.g. iPS
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Rheumatology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cell Biology (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Physical Education & Sports Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Developmental Biology & Embryology (AREA)
- Virology (AREA)
- Epidemiology (AREA)
Abstract
Description
本願は、2017年1月11日に出願した米国仮出願第62/445,133号の恩典を請求するものであり、前記仮出願は、その全体が参照により本明細書に組み入れられる。
本開示の実施形態は、少なくとも細胞生物学、分子生物学、生化学および医学の分野に関する。
多血小板血漿との培養は線維芽細胞の免疫抑制マーカーPD-1L発現を増進する
線維芽細胞を多血小板血漿(PRP)とともに培養して、治療使用のための増強された線維芽細胞を産生する。包皮線維芽細胞、ヒト骨髄MSCおよびヒト脂肪MSCをATCCから入手し、10%ウシ胎仔血清を含有するDMEM培地において、健常ドナーから生成した図1に表記のPRP濃度で培養した。細胞を48時間にわたって培養した。PD-抗PDL1-PEまたはアイソタイプ対照(Becton Dickenson、Franklin Lakes、NJ)を、製造業者の説明書に従って染色に使用した。Live/Dead Fixable近赤外色素(live/dead fixable near-infrared dye)(Invitrogen)を使用して、死細胞を排除した。ゲートした生細胞の蛍光を平均蛍光強度(MFI)として定量した。図1から分かるように、PD-L1発現の増加が線維芽細胞において独特に観察された。
多血小板血漿との培養はT細胞活性化を抑制する線維芽細胞の能力を増強する
線維芽細胞をPRPとともに培養して、治療使用のための増強された線維芽細胞を産生する。包皮線維芽細胞、ヒト骨髄MSCおよびヒト脂肪MSCをATCCから入手し、10%ウシ胎仔血清を含有するDMEM培地において、健常ドナーから生成した下記の多血小板血漿(PRP)濃度で培養した。細胞を48時間培養した。その後、細胞を同種異系末梢血単核細胞とともに播種し、1ml当たり0.5マイクログラムの植物性血液凝集素で刺激した。細胞を72時間にわたって共培養し、最後の12時間の培養中に1マイクロキューリーの滴定チミジンを添加した。増殖をシンチレーション測定によって評価した。観察された通り、PRPの添加は、線維画細胞の免疫抑制活性を独特に増強した。
多血小板血漿との培養はインターフェロンガンマのT細胞産生を抑制する線維芽細胞の能力を増強する
線維芽細胞を多血小板血漿(PRP)とともに培養して、治療使用のための増強された線維芽細胞を産生する。包皮線維芽細胞、ヒト骨髄MSCおよびヒト脂肪MSCをATCCから入手し、10%ウシ胎仔血清を含有するDMEM培地において、健常ドナーから生成した下記の多血小板血漿(PRP)濃度で培養した。細胞を48時間培養した。その後、細胞を同種異系末梢血単核細胞とともに播種し、1ml当たり0.5マイクログラムの植物性血液凝集素で刺激した。細胞を48時間にわたって共培養し、インターフェロンガンマ産生の評価をELISAによって行った。観察された通り、インターフェロンガンマ産生の減少が、PRP処理線維芽細胞において独特に観察された。
本明細書で言及したすべての特許および公表文献は、本発明が属する技術分野の当業者のレベルを示す。すべての特許および公表文献は、個々の公表文献各々が、それら全体が参照により組み入れられていると具体的におよび個々に示されている場合と同程度に、参照により組み入れられる。
米国特許第5,165,928号明細書
1.Frymoyer JW,D.C.,The economics of spinal disorders.In Frymoyer JW,Ducker TB,Hadler NM,et al.,eds.The adult spine:principles and practice.Philadelphia,PA:Lippincott-Raven,1997:143-50.
本開示およびその利点を詳細に説明してきたが、添付の特許請求の範囲によって定義される通りの設計の趣旨および精神から逸脱することなく、この中で様々な変更、置換および代替を行うことができることは、理解されるはずである。さらに、本願の範囲は、本明細書に記載の工程、機械、製造、組成物、手段、方法およびステップの特定の実施形態に限定されることを意図したものではない。本開示から当業者には容易に理解されるであろうが、本開示に記載の対応する実施形態と実質的に同じ機能を果すまたは実質的に同じ結果を達成する、現在存在するまたは後に開発される工程、機械、製造、組成物、手段、方法またはステップを本発明に従って用いることができるだろう。したがって、添付の特許請求の範囲は、それらの範囲内にそのような工程、機械、製造、組成物、手段、方法またはステップを含むことを意図したものである。
Claims (1)
- 明細書又は図面に記載の発明。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2024007119A JP2024041996A (ja) | 2017-01-11 | 2024-01-22 | 線維芽細胞治療活性を増強する方法 |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201762445133P | 2017-01-11 | 2017-01-11 | |
US62/445,133 | 2017-01-11 | ||
PCT/US2018/013357 WO2018132594A1 (en) | 2017-01-11 | 2018-01-11 | Methods of enhancing fibroblast therapeutic activity |
JP2019558339A JP7333272B2 (ja) | 2017-01-11 | 2018-01-11 | 線維芽細胞治療活性を増強する方法 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019558339A Division JP7333272B2 (ja) | 2017-01-11 | 2018-01-11 | 線維芽細胞治療活性を増強する方法 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2024007119A Division JP2024041996A (ja) | 2017-01-11 | 2024-01-22 | 線維芽細胞治療活性を増強する方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2022024047A true JP2022024047A (ja) | 2022-02-08 |
JP7426368B2 JP7426368B2 (ja) | 2024-02-01 |
Family
ID=62782706
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019558339A Active JP7333272B2 (ja) | 2017-01-11 | 2018-01-11 | 線維芽細胞治療活性を増強する方法 |
JP2021184431A Active JP7426368B2 (ja) | 2017-01-11 | 2021-11-12 | 線維芽細胞治療活性を増強する方法 |
JP2024007119A Pending JP2024041996A (ja) | 2017-01-11 | 2024-01-22 | 線維芽細胞治療活性を増強する方法 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019558339A Active JP7333272B2 (ja) | 2017-01-11 | 2018-01-11 | 線維芽細胞治療活性を増強する方法 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2024007119A Pending JP2024041996A (ja) | 2017-01-11 | 2024-01-22 | 線維芽細胞治療活性を増強する方法 |
Country Status (7)
Country | Link |
---|---|
US (2) | US11034934B2 (ja) |
EP (1) | EP3568465A4 (ja) |
JP (3) | JP7333272B2 (ja) |
CN (1) | CN110337490A (ja) |
AU (2) | AU2018207541B2 (ja) |
CA (1) | CA3049768A1 (ja) |
WO (1) | WO2018132594A1 (ja) |
Families Citing this family (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA3049768A1 (en) * | 2017-01-11 | 2018-07-19 | Spinalcyte, Llc | Methods of enhancing fibroblast therapeutic activity |
CA3085984A1 (en) | 2017-12-20 | 2019-06-27 | Figene, Llc | Augmentation of fibroblast regenerative activity |
CN109136169A (zh) * | 2018-08-09 | 2019-01-04 | 上海交通大学医学院附属第九人民医院 | 一种皮肤成纤维细胞转变为人工椎间盘的系统及其使用方法 |
AU2019371464A1 (en) * | 2018-11-04 | 2021-06-03 | Figene, Llc | Treatment of cerebral hypoxia including stroke, chronic traumatic encephalopathy, and traumatic brain injury |
EP3873495B1 (en) * | 2018-11-04 | 2024-06-26 | Figene, LLC | Methods and compositions for treatment of type 1 diabetes using fibroblasts as facilitators of islet engraftment |
AU2019374153A1 (en) * | 2018-11-04 | 2021-06-10 | Figene, Llc | Treatment of cachexia using fibroblast cells and products thereof |
WO2020097418A1 (en) * | 2018-11-09 | 2020-05-14 | Figene, Llc | Regenerative abscopal effects |
US20220110979A1 (en) * | 2019-01-11 | 2022-04-14 | Figene, Llc | Fibroblast regenerative cells |
CA3126929A1 (en) * | 2019-01-17 | 2020-07-23 | Figene, Llc | Fibroblasts and microvesicles thereof for reduction of toxicity associated with cancer immunotherapy |
WO2020223148A1 (en) * | 2019-04-27 | 2020-11-05 | Figene, Llc | Enhancement of fibroblast therapeutic activity by t cell modulation |
AU2020302908A1 (en) * | 2019-06-28 | 2022-02-24 | Figene, Llc | Administration of fibroblasts and derivatives thereof for treatment of type 2 diabetes |
WO2021055448A1 (en) * | 2019-09-16 | 2021-03-25 | Figene, Llc | Treatment of disc degenerative disease and stimulation of proteoglycan synthesis by fibroblast conditioned media and formulations thereof |
US20230151329A1 (en) * | 2019-10-15 | 2023-05-18 | Figene, Llc | Fibroblast-based immunotherapy of graves disease |
EP4081261A4 (en) * | 2019-12-26 | 2024-04-24 | Figene, LLC | INCREASED FIBROBLAST-MEDIATED REGENERATION OF INTRAVERTEBRAL DISCS |
WO2021211386A1 (en) * | 2020-04-13 | 2021-10-21 | Figene, Llc | Treatment of erectile dysfunction by fibroblast administration |
WO2021232064A2 (en) * | 2020-05-14 | 2021-11-18 | Figene, Llc | Treatment of ovarian failure using regenerative cells |
CN111560346A (zh) * | 2020-05-21 | 2020-08-21 | 福建省海西细胞生物工程有限公司 | 一种外植体粘附法高效提取增殖自体成纤维细胞的方法 |
US20230340416A1 (en) * | 2020-07-14 | 2023-10-26 | Figene, Llc | Augmentation of fibroblast therapeutic activity by complement blockade and/or inhibition |
CN113755430B (zh) * | 2021-09-09 | 2023-08-18 | 北京益华生物科技有限公司 | 一种高表达afgf的方法 |
CN117660325B (zh) * | 2024-01-31 | 2024-04-19 | 苏州科为康生物医药科技有限公司 | 一种制备脐带血msc的培养基及其方法 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2010001578A1 (ja) * | 2008-06-30 | 2010-01-07 | 国立大学法人東京大学 | 骨成長因子を吸着し,その活性を阻害しない骨補填剤 |
Family Cites Families (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5192553A (en) | 1987-11-12 | 1993-03-09 | Biocyte Corporation | Isolation and preservation of fetal and neonatal hematopoietic stem and progenitor cells of the blood and methods of therapeutic use |
US5165928A (en) | 1988-11-14 | 1992-11-24 | Cornell Research Foundation, Inc. | Biological control of phytophthora by gliocladium |
US5599558A (en) | 1989-09-15 | 1997-02-04 | Curative Technologies, Inc. | Selecting amounts of platelet releasate for efficacious treatment of tissue |
US5585007A (en) | 1994-12-07 | 1996-12-17 | Plasmaseal Corporation | Plasma concentrate and tissue sealant methods and apparatuses for making concentrated plasma and/or tissue sealant |
US5614204A (en) | 1995-01-23 | 1997-03-25 | The Regents Of The University Of California | Angiographic vascular occlusion agents and a method for hemostatic occlusion |
JPH11508813A (ja) | 1995-06-06 | 1999-08-03 | クウォンティック バイオメディカル パートナーズ | 血漿を濃縮するための装置及び方法 |
AU2763099A (en) | 1998-06-22 | 2000-01-10 | Charles E. Worden | Enriched platelet wound healant |
US6328762B1 (en) * | 1999-04-27 | 2001-12-11 | Sulzer Biologics, Inc. | Prosthetic grafts |
US20090074729A2 (en) * | 1999-11-05 | 2009-03-19 | Donald Kleinsek | Augmentation and repair of spincter defects with cells including fibroblasts |
EP1286707A2 (en) | 2000-02-18 | 2003-03-05 | Regeneration Technologies, Inc. | Implantable tissues infused with growth factors and other additives |
US6649072B2 (en) | 2001-11-16 | 2003-11-18 | Robert Brandt | Method for producing autologous platelet-rich plasma |
ITMI20021917A1 (it) * | 2002-09-10 | 2004-03-11 | New Dawn Consultores E Servicos L Da | Attivatore per la formazione di gel piastrinico, gel di plasma povero di piastrine o gel di plasma ricco di piastrine. |
JP2006230418A (ja) | 2003-05-23 | 2006-09-07 | M D Bio Inc | 充填材料 |
WO2005065419A2 (en) * | 2003-12-29 | 2005-07-21 | Am Biosolutions | Method of culturing cells |
JP4364696B2 (ja) | 2004-03-30 | 2009-11-18 | ニプロ株式会社 | 組織または器官再生用材料 |
JP4982865B2 (ja) * | 2005-06-29 | 2012-07-25 | 国立大学法人名古屋大学 | 皮膚組織改善材及びその利用 |
CN102389344B (zh) | 2006-02-07 | 2015-12-16 | 脊柱赛特有限公司 | 采用机械应变使人皮肤成纤维细胞发生软骨形成分化的方法 |
CN101472622B (zh) | 2006-04-19 | 2014-11-26 | 国立大学法人名古屋大学 | 用于牙周软组织再生的组合物及其制备方法 |
EP2209890A4 (en) * | 2006-12-13 | 2011-11-02 | Tgr Biosciences Pty Ltd | STIMULATION OF PRODUCTION OF EXTRACELLULAR MEDIA WITH FIBROBLAST CELLS AND / OR STIMULATION OF MIGRATION OF FIBROBLAST CELLS IN A BIOLOGICAL SYSTEM |
WO2010093655A2 (en) | 2009-02-10 | 2010-08-19 | University Of Dayton | Enhanced method for producing stem-like cells from somatic cells |
KR101114712B1 (ko) | 2009-10-23 | 2012-02-29 | 세원셀론텍(주) | 염화칼슘용액과 제1형 콜라겐으로 혈소판풍부혈장(prp)을 활성화하여 조직재생을 유도하는 조성물의 제조방법 |
CN108014339A (zh) * | 2011-11-09 | 2018-05-11 | 脊核细胞有限责任公司 | 用于治疗椎间盘退变性疾病的成纤维细胞 |
AU2013299505B2 (en) | 2012-08-10 | 2016-12-22 | Spinalcyte, Llc | Generation of cartilage ex vivo from fibroblasts |
US20140356893A1 (en) * | 2013-06-04 | 2014-12-04 | Allan Mishra | Compositions and methods for using platelet-rich plasma for drug discovery, cell nuclear reprogramming, proliferation or differentiation |
WO2014204806A2 (en) | 2013-06-19 | 2014-12-24 | Spinalcyte, Llc | Adipose cells for chondrocyte applications |
US11819555B2 (en) | 2013-09-09 | 2023-11-21 | Figene, Llc | Gene therapy for the regeneration of chondrocytes or cartilage type cells |
CN104611289A (zh) * | 2015-01-13 | 2015-05-13 | 广州赛奕德生物技术有限公司 | 自体表皮细胞和成纤维细胞同时制备方法及其生物美容产品 |
WO2017123951A1 (en) | 2016-01-14 | 2017-07-20 | Spinacyte, Llc | Cellular blend for the regeneration of chondrocytes or cartilage type cells |
CA3049768A1 (en) * | 2017-01-11 | 2018-07-19 | Spinalcyte, Llc | Methods of enhancing fibroblast therapeutic activity |
EP3612158A4 (en) | 2017-04-19 | 2021-01-27 | Figene, LLC | STIMULATION OF ANGIOGENESIS BY EXOSOMES FROM FIBROBLASTS |
JP7387603B2 (ja) * | 2017-11-29 | 2023-11-28 | フィジーン、エルエルシー | 活性化のための線維芽細胞と免疫細胞との相互作用及びそれらの使用 |
CA3085984A1 (en) | 2017-12-20 | 2019-06-27 | Figene, Llc | Augmentation of fibroblast regenerative activity |
-
2018
- 2018-01-11 CA CA3049768A patent/CA3049768A1/en active Pending
- 2018-01-11 AU AU2018207541A patent/AU2018207541B2/en active Active
- 2018-01-11 CN CN201880013348.0A patent/CN110337490A/zh active Pending
- 2018-01-11 WO PCT/US2018/013357 patent/WO2018132594A1/en unknown
- 2018-01-11 US US15/868,420 patent/US11034934B2/en active Active
- 2018-01-11 EP EP18738916.8A patent/EP3568465A4/en active Pending
- 2018-01-11 JP JP2019558339A patent/JP7333272B2/ja active Active
-
2021
- 2021-05-20 US US17/303,133 patent/US20210309971A1/en active Pending
- 2021-11-12 JP JP2021184431A patent/JP7426368B2/ja active Active
-
2024
- 2024-01-22 JP JP2024007119A patent/JP2024041996A/ja active Pending
- 2024-02-22 AU AU2024201176A patent/AU2024201176A1/en active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2010001578A1 (ja) * | 2008-06-30 | 2010-01-07 | 国立大学法人東京大学 | 骨成長因子を吸着し,その活性を阻害しない骨補填剤 |
Non-Patent Citations (1)
Title |
---|
BRAUN, H. J. ET AL.: "The effect of platelet-rich plasma formulations and blood products on human synoviocytes: implicatio", THE AMERICAN JOURNAL OF SPORTS MEDICINE, vol. 42(5), JPN6023020552, 2014, pages 1204 - 1210, ISSN: 0005064325 * |
Also Published As
Publication number | Publication date |
---|---|
WO2018132594A1 (en) | 2018-07-19 |
AU2018207541A1 (en) | 2019-08-01 |
JP7333272B2 (ja) | 2023-08-24 |
CN110337490A (zh) | 2019-10-15 |
EP3568465A4 (en) | 2021-01-27 |
JP2024041996A (ja) | 2024-03-27 |
JP7426368B2 (ja) | 2024-02-01 |
CA3049768A1 (en) | 2018-07-19 |
US11034934B2 (en) | 2021-06-15 |
AU2018207541B2 (en) | 2023-12-21 |
AU2024201176A1 (en) | 2024-03-14 |
JP2020503901A (ja) | 2020-02-06 |
EP3568465A1 (en) | 2019-11-20 |
US20180195044A1 (en) | 2018-07-12 |
US20210309971A1 (en) | 2021-10-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7426368B2 (ja) | 線維芽細胞治療活性を増強する方法 | |
US20230313136A1 (en) | Abcb5 positive mesenchymal stem cells as immunomodulators | |
JP4441115B2 (ja) | ヒト非自己間葉幹細胞を使用する方法と利用 | |
Lee et al. | CTGF directs fibroblast differentiation from human mesenchymal stem/stromal cells and defines connective tissue healing in a rodent injury model | |
RU2435846C2 (ru) | Применение стромальных стволовых клеток жировой ткани для лечения свищей | |
ES2645012T3 (es) | Método para potenciar la proliferación y/o supervivencia de las células precursoras mesenquimales (MPC) | |
US10675307B2 (en) | Compositions comprising perivascular stem cells and nell-1 protein | |
JP2002506082A5 (ja) | ||
JP6193214B2 (ja) | 歯髄由来の多能性幹細胞の製造方法 | |
Fu et al. | Comparative study of the biological characteristics of mesenchymal stem cells from bone marrow and peripheral blood of rats | |
CA2617628A1 (en) | Use of adipose tissue-derived stromal cells in spinal fusion | |
Yin et al. | Cell‐Based Therapies for Degenerative Musculoskeletal Diseases | |
O'HEERON et al. | Patent 3049768 Summary | |
WO2021039882A1 (ja) | 培養基材を用いたTie2陽性幹/前駆細胞を含む細胞集団の培養方法およびその利用 | |
US20230372402A1 (en) | Cytokine primed regenerative cells for treatment of ovarian failure | |
AU2013204421B2 (en) | ABCB5 positive mesenchymal stem cells as immunomodulators | |
Bourgine | Combination of cell immortalization and apoptosis induction to engineer decellularized matrices as bone graft materials |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20211115 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220909 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20221129 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20230307 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230523 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20230815 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20231023 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20231114 |
|
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: 20240109 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20240122 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7426368 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |