JP6495934B2 - グラフト移植および組織工学的手順におけるｆｇｆ−１８ - Google Patents
グラフト移植および組織工学的手順におけるｆｇｆ−１８ Download PDFInfo
- Publication number
- JP6495934B2 JP6495934B2 JP2016553431A JP2016553431A JP6495934B2 JP 6495934 B2 JP6495934 B2 JP 6495934B2 JP 2016553431 A JP2016553431 A JP 2016553431A JP 2016553431 A JP2016553431 A JP 2016553431A JP 6495934 B2 JP6495934 B2 JP 6495934B2
- Authority
- JP
- Japan
- Prior art keywords
- cartilage
- fgf
- culture
- compound
- rhfgf18
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 102000003977 fibroblast growth factor 18 Human genes 0.000 title claims description 143
- 108090000370 fibroblast growth factor 18 Proteins 0.000 title claims description 143
- 238000000034 method Methods 0.000 title claims description 84
- 238000002054 transplantation Methods 0.000 title description 25
- 210000000845 cartilage Anatomy 0.000 claims description 192
- 210000004027 cell Anatomy 0.000 claims description 117
- 150000001875 compounds Chemical class 0.000 claims description 94
- 230000002648 chondrogenic effect Effects 0.000 claims description 72
- 238000012258 culturing Methods 0.000 claims description 56
- 210000001612 chondrocyte Anatomy 0.000 claims description 54
- 241000124008 Mammalia Species 0.000 claims description 45
- 239000001963 growth medium Substances 0.000 claims description 44
- 239000000463 material Substances 0.000 claims description 35
- 210000001519 tissue Anatomy 0.000 claims description 25
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 229920001184 polypeptide Polymers 0.000 claims description 10
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 10
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 10
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 8
- 210000002901 mesenchymal stem cell Anatomy 0.000 claims description 3
- 230000007547 defect Effects 0.000 description 53
- 238000011282 treatment Methods 0.000 description 52
- 201000008482 osteoarthritis Diseases 0.000 description 43
- 230000014509 gene expression Effects 0.000 description 35
- 208000015100 cartilage disease Diseases 0.000 description 32
- 102000000503 Collagen Type II Human genes 0.000 description 24
- 108010041390 Collagen Type II Proteins 0.000 description 24
- 230000010354 integration Effects 0.000 description 24
- 206010007710 Cartilage injury Diseases 0.000 description 23
- 238000007792 addition Methods 0.000 description 23
- 102000012422 Collagen Type I Human genes 0.000 description 22
- 108010022452 Collagen Type I Proteins 0.000 description 22
- 206010061762 Chondropathy Diseases 0.000 description 21
- 230000008439 repair process Effects 0.000 description 21
- 201000009859 Osteochondrosis Diseases 0.000 description 19
- 101150106167 SOX9 gene Proteins 0.000 description 17
- 238000002513 implantation Methods 0.000 description 16
- 208000014674 injury Diseases 0.000 description 16
- 239000002609 medium Substances 0.000 description 16
- 238000004264 monolayer culture Methods 0.000 description 16
- 239000011159 matrix material Substances 0.000 description 14
- 230000000694 effects Effects 0.000 description 13
- 230000006378 damage Effects 0.000 description 12
- 230000001172 regenerating effect Effects 0.000 description 12
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 11
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 11
- 229960002591 hydroxyproline Drugs 0.000 description 11
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 11
- 102000008186 Collagen Human genes 0.000 description 10
- 108010035532 Collagen Proteins 0.000 description 10
- 229920001436 collagen Polymers 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- 229950002135 sprifermin Drugs 0.000 description 10
- 208000027418 Wounds and injury Diseases 0.000 description 9
- 238000000338 in vitro Methods 0.000 description 9
- 239000013589 supplement Substances 0.000 description 9
- 150000001413 amino acids Chemical group 0.000 description 8
- 210000001188 articular cartilage Anatomy 0.000 description 8
- 210000000988 bone and bone Anatomy 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 230000035755 proliferation Effects 0.000 description 8
- 238000001356 surgical procedure Methods 0.000 description 8
- 230000008569 process Effects 0.000 description 7
- 239000002356 single layer Substances 0.000 description 7
- 230000009469 supplementation Effects 0.000 description 7
- 230000008733 trauma Effects 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 230000003442 weekly effect Effects 0.000 description 6
- 208000013201 Stress fracture Diseases 0.000 description 5
- 206010003246 arthritis Diseases 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 210000003035 hyaline cartilage Anatomy 0.000 description 5
- 210000001503 joint Anatomy 0.000 description 5
- 239000003550 marker Substances 0.000 description 5
- 230000003349 osteoarthritic effect Effects 0.000 description 5
- OARRHUQTFTUEOS-UHFFFAOYSA-N safranin Chemical compound [Cl-].C=12C=C(N)C(C)=CC2=NC2=CC(C)=C(N)C=C2[N+]=1C1=CC=CC=C1 OARRHUQTFTUEOS-UHFFFAOYSA-N 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- 241000283690 Bos taurus Species 0.000 description 4
- 241000588724 Escherichia coli Species 0.000 description 4
- 102100035323 Fibroblast growth factor 18 Human genes 0.000 description 4
- 101000878128 Homo sapiens Fibroblast growth factor 18 Proteins 0.000 description 4
- 101000958041 Homo sapiens Musculin Proteins 0.000 description 4
- 125000000539 amino acid group Chemical group 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 210000001185 bone marrow Anatomy 0.000 description 4
- 239000006143 cell culture medium Substances 0.000 description 4
- 230000004663 cell proliferation Effects 0.000 description 4
- 230000008021 deposition Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 239000007943 implant Substances 0.000 description 4
- 230000037211 monthly cycles Effects 0.000 description 4
- 238000003753 real-time PCR Methods 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 102000030746 Collagen Type X Human genes 0.000 description 3
- 108010022510 Collagen Type X Proteins 0.000 description 3
- 102000029816 Collagenase Human genes 0.000 description 3
- 108060005980 Collagenase Proteins 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- 206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 230000022159 cartilage development Effects 0.000 description 3
- 229960002424 collagenase Drugs 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 210000000968 fibrocartilage Anatomy 0.000 description 3
- 238000010562 histological examination Methods 0.000 description 3
- 102000046949 human MSC Human genes 0.000 description 3
- 201000002215 juvenile rheumatoid arthritis Diseases 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- 230000002085 persistent effect Effects 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 210000005065 subchondral bone plate Anatomy 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000282836 Camelus dromedarius Species 0.000 description 2
- 208000001148 Cartilage Fractures Diseases 0.000 description 2
- 241000283073 Equus caballus Species 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 208000007353 Hip Osteoarthritis Diseases 0.000 description 2
- 208000003456 Juvenile Arthritis Diseases 0.000 description 2
- 208000003947 Knee Osteoarthritis Diseases 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 206010073853 Osteochondral fracture Diseases 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 241000009328 Perro Species 0.000 description 2
- 206010065159 Polychondritis Diseases 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 102000016611 Proteoglycans Human genes 0.000 description 2
- 108010067787 Proteoglycans Proteins 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 230000000735 allogeneic effect Effects 0.000 description 2
- 239000003124 biologic agent Substances 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000012620 biological material Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000011227 chondrocyte hypertrophy Effects 0.000 description 2
- 208000019069 chronic childhood arthritis Diseases 0.000 description 2
- 238000010968 computed tomography angiography Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 210000004276 hyalin Anatomy 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 210000003127 knee Anatomy 0.000 description 2
- 238000013150 knee replacement Methods 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 210000000963 osteoblast Anatomy 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- -1 trFGF-18 Chemical class 0.000 description 2
- 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 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- 102000016284 Aggrecans Human genes 0.000 description 1
- 108010067219 Aggrecans Proteins 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 235000007319 Avena orientalis Nutrition 0.000 description 1
- 244000075850 Avena orientalis Species 0.000 description 1
- 206010008685 Chondritis Diseases 0.000 description 1
- 241001391944 Commicarpus scandens Species 0.000 description 1
- 235000015655 Crocus sativus Nutrition 0.000 description 1
- 244000124209 Crocus sativus Species 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 108010067770 Endopeptidase K Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 208000004575 Infectious Arthritis Diseases 0.000 description 1
- 208000012659 Joint disease Diseases 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 102000055008 Matrilin Proteins Human genes 0.000 description 1
- 108010072582 Matrilin Proteins Proteins 0.000 description 1
- 101100096242 Mus musculus Sox9 gene Proteins 0.000 description 1
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 1
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 238000011529 RT qPCR Methods 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
- 229930003268 Vitamin C Natural products 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
- 230000001195 anabolic effect Effects 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 238000010256 biochemical assay Methods 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 208000002849 chondrocalcinosis Diseases 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 229940096422 collagen type i Drugs 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000002591 computed tomography Methods 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000032459 dedifferentiation Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 210000002745 epiphysis Anatomy 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 238000009778 extrusion testing Methods 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 239000002657 fibrous material Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000001624 hip Anatomy 0.000 description 1
- 210000004394 hip joint Anatomy 0.000 description 1
- 238000007825 histological assay Methods 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 230000008407 joint function Effects 0.000 description 1
- 210000002414 leg Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000006371 metabolic abnormality Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 238000012148 non-surgical treatment Methods 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 238000000554 physical therapy Methods 0.000 description 1
- 230000017363 positive regulation of growth Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000003651 pro-proliferative effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 208000009169 relapsing polychondritis Diseases 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 235000013974 saffron Nutrition 0.000 description 1
- 239000004248 saffron Substances 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 201000001223 septic arthritis Diseases 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
- A61L27/3612—Cartilage, synovial fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
-
- 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
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3641—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the site of application in the body
- A61L27/3645—Connective tissue
- A61L27/3654—Cartilage, e.g. meniscus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3683—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
- A61L27/3687—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
- C07K14/50—Fibroblast growth factor [FGF]
-
- 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
- C12N5/0655—Chondrocytes; Cartilage
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/06—Materials or treatment for tissue regeneration for cartilage reconstruction, e.g. meniscus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/24—Materials or treatment for tissue regeneration for joint reconstruction
-
- 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
- C12N2501/119—Other fibroblast growth factors, e.g. FGF-4, FGF-8, FGF-10
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2513/00—3D culture
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Transplantation (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Dermatology (AREA)
- Botany (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Rheumatology (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Urology & Nephrology (AREA)
- General Chemical & Material Sciences (AREA)
- Vascular Medicine (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmacology & Pharmacy (AREA)
- Biophysics (AREA)
- Toxicology (AREA)
- Heart & Thoracic Surgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Cardiology (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14000599 | 2014-02-20 | ||
| EP14000599.2 | 2014-02-20 | ||
| PCT/EP2015/053639 WO2015124735A1 (en) | 2014-02-20 | 2015-02-20 | Fgf-18 in graft transplantation and tissue engineering procedures |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2017508523A JP2017508523A (ja) | 2017-03-30 |
| JP2017508523A5 JP2017508523A5 (enExample) | 2018-02-22 |
| JP6495934B2 true JP6495934B2 (ja) | 2019-04-03 |
Family
ID=50151087
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016553431A Active JP6495934B2 (ja) | 2014-02-20 | 2015-02-20 | グラフト移植および組織工学的手順におけるｆｇｆ−１８ |
Country Status (17)
| Country | Link |
|---|---|
| US (2) | US20170056554A1 (enExample) |
| EP (1) | EP3107591B1 (enExample) |
| JP (1) | JP6495934B2 (enExample) |
| KR (1) | KR102437057B1 (enExample) |
| CN (1) | CN106232153B (enExample) |
| AR (1) | AR099557A1 (enExample) |
| AU (1) | AU2015220781B2 (enExample) |
| BR (1) | BR112016018704B1 (enExample) |
| CA (1) | CA2938795A1 (enExample) |
| ES (1) | ES2676318T3 (enExample) |
| IL (1) | IL247105B (enExample) |
| MX (1) | MX2016010873A (enExample) |
| NZ (1) | NZ723169A (enExample) |
| RU (1) | RU2682159C2 (enExample) |
| SG (1) | SG11201606696UA (enExample) |
| WO (1) | WO2015124735A1 (enExample) |
| ZA (1) | ZA201605549B (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10086112B2 (en) | 2014-02-20 | 2018-10-02 | Merck Patent Gmbh | Implant comprising FGF-18 |
| MX2016010871A (es) | 2014-02-20 | 2016-11-17 | Merck Patent Gmbh | Regimen de dosificacion del compuesto de factor de crecimiento de fibroblastos 18. |
| JP6787904B2 (ja) | 2015-01-29 | 2020-11-18 | アレス トレーディング ソシエテ アノニム | 高度に正に荷電したタンパク質のイムノアッセイ |
| CN107058217A (zh) * | 2017-01-22 | 2017-08-18 | 广州赛莱拉干细胞科技股份有限公司 | 一种软骨细胞的增殖培养基及增殖培养方法 |
| CA3056155A1 (en) * | 2017-03-17 | 2018-09-20 | Merck Patent Gmbh | Cartilage preservation media |
| HUE058848T2 (hu) | 2017-09-29 | 2022-09-28 | Merck Patent Gmbh | FGF-18 vegyületre vonatkozó válaszkészség elõrejelzésére szolgáló gyulladásos biomarkerek |
| SI3687558T1 (sl) | 2017-09-29 | 2022-08-31 | Merck Patent Gmbh | Presnovni biooznačevalci za napovedovanje odzivnosti na spojino FGF-18 |
| EP3850113B1 (en) | 2018-09-10 | 2024-04-03 | Merck Patent GmbH | Markers useful in enrichment strategies for the treatment of osteoarthritis |
| CN113244413B (zh) * | 2021-06-28 | 2021-10-26 | 深圳市瑞吉生物科技有限公司 | 一种mRNA剂型的骨关节炎药物制剂及其制备方法和应用 |
| IT202300012807A1 (it) * | 2023-06-26 | 2024-12-26 | Umberto Parri | Protesi d'anca in biomateriali e procedimento di fabbricazione |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6511958B1 (en) * | 1997-08-14 | 2003-01-28 | Sulzer Biologics, Inc. | Compositions for regeneration and repair of cartilage lesions |
| US20140193468A1 (en) * | 2001-03-23 | 2014-07-10 | Histogenics Corporation | Methods for preparation of neo-cartilage constructs |
| EP1551426B1 (en) * | 2002-10-07 | 2014-06-25 | ZymoGenetics, Inc. | Methods of administering fgf18 |
| AR062522A1 (es) * | 2006-08-25 | 2008-11-12 | Ares Trading Sa | Tratamiento de desordenes en cartilagos |
| MY148277A (en) * | 2006-08-25 | 2013-03-29 | Ares Trading Sa | Treatment of cartilage disorders with fgf-18 |
| JP5388233B2 (ja) * | 2011-01-19 | 2014-01-15 | 富士ソフト株式会社 | 再生軟骨の軟骨特性を評価する方法 |
-
2015
- 2015-02-20 CN CN201580020522.0A patent/CN106232153B/zh active Active
- 2015-02-20 NZ NZ723169A patent/NZ723169A/en unknown
- 2015-02-20 CA CA2938795A patent/CA2938795A1/en active Pending
- 2015-02-20 WO PCT/EP2015/053639 patent/WO2015124735A1/en not_active Ceased
- 2015-02-20 US US15/120,136 patent/US20170056554A1/en not_active Abandoned
- 2015-02-20 AU AU2015220781A patent/AU2015220781B2/en active Active
- 2015-02-20 ES ES15705823.1T patent/ES2676318T3/es active Active
- 2015-02-20 EP EP15705823.1A patent/EP3107591B1/en active Active
- 2015-02-20 RU RU2016137290A patent/RU2682159C2/ru active
- 2015-02-20 BR BR112016018704-0A patent/BR112016018704B1/pt active IP Right Grant
- 2015-02-20 SG SG11201606696UA patent/SG11201606696UA/en unknown
- 2015-02-20 KR KR1020167025249A patent/KR102437057B1/ko active Active
- 2015-02-20 AR ARP150100506A patent/AR099557A1/es active IP Right Grant
- 2015-02-20 JP JP2016553431A patent/JP6495934B2/ja active Active
- 2015-02-20 MX MX2016010873A patent/MX2016010873A/es active IP Right Grant
-
2016
- 2016-08-04 IL IL247105A patent/IL247105B/en active IP Right Grant
- 2016-08-10 ZA ZA2016/05549A patent/ZA201605549B/en unknown
-
2022
- 2022-06-16 US US17/842,762 patent/US20220378981A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CN106232153A (zh) | 2016-12-14 |
| CA2938795A1 (en) | 2015-08-27 |
| CN106232153B (zh) | 2020-01-17 |
| KR20160124149A (ko) | 2016-10-26 |
| IL247105A0 (en) | 2016-09-29 |
| BR112016018704A2 (pt) | 2017-10-17 |
| AR099557A1 (es) | 2016-08-03 |
| BR112016018704B1 (pt) | 2021-01-05 |
| AU2015220781B2 (en) | 2018-05-24 |
| IL247105B (en) | 2020-02-27 |
| ZA201605549B (en) | 2018-12-19 |
| NZ723169A (en) | 2023-05-26 |
| AU2015220781A1 (en) | 2016-09-01 |
| EP3107591B1 (en) | 2018-04-18 |
| ES2676318T3 (es) | 2018-07-18 |
| KR102437057B1 (ko) | 2022-08-26 |
| JP2017508523A (ja) | 2017-03-30 |
| US20170056554A1 (en) | 2017-03-02 |
| RU2682159C2 (ru) | 2019-03-15 |
| RU2016137290A (ru) | 2018-03-23 |
| US20220378981A1 (en) | 2022-12-01 |
| WO2015124735A1 (en) | 2015-08-27 |
| MX2016010873A (es) | 2016-11-17 |
| SG11201606696UA (en) | 2016-09-29 |
| RU2016137290A3 (enExample) | 2018-09-07 |
| EP3107591A1 (en) | 2016-12-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6495934B2 (ja) | グラフト移植および組織工学的手順におけるｆｇｆ−１８ | |
| JP5795577B2 (ja) | 組織修復のための固形形態 | |
| US9700583B2 (en) | Methods and compositions for optimized expansion and implantation of mesenchymal stem cells | |
| DE60018576T2 (de) | In vitro heilung von knochen- und/oder knorpelschäden | |
| CN102614546B (zh) | 用于组织修复和生物人造组织工程的细胞片及其制备方法 | |
| US11801331B2 (en) | Composition for cartilage regeneration and preparing thereof | |
| JP2001502905A (ja) | ホウォートンゼリーから分離した細胞を用いた軟骨組織の形成 | |
| WO2007127436A2 (en) | Methods and compositions for repairing cartilage | |
| Cheng et al. | A novel animal model treated with tooth extraction to repair the full-thickness defects in the mandible of rabbits | |
| CN102325536A (zh) | 促进无血管组织修复的方法和组合物 | |
| TWI450735B (zh) | 修補軟骨組織之組合物及其製備方法 | |
| US20060212125A1 (en) | Bone repairing material using a chondrocyte having the potential for hypertrophy and a scaffold | |
| EP1945756A2 (en) | Method for non-autologous cartilage regeneration | |
| AU2015295304A1 (en) | Transdifferentiated tissue graft | |
| HK1231785B (zh) | 用於移植和组织工程手术的fgf-18 | |
| HK1231785A1 (en) | Fgf-18 in graft transplantation and tissue engineering procedures | |
| WO2024237186A1 (ja) | 難治性骨欠損の予防又は治療用医薬組成物 | |
| CN115581811A (zh) | 一种自体组织工程活细胞睑板替代物及其制备方法和应用 | |
| US20200128812A1 (en) | Cartilage preservation media | |
| Caviglia | Tissue engineering in musculoskeletal problems related to haemophilia | |
| Haddad et al. | Tissue engineering of the temporomandibular joint: Where do we stand now? | |
| Kinner et al. | Tissue Engineering Alternatives to Joint Replacement | |
| Park et al. | The Effect of Cultured Perichondrial Cell Sheet Covered Highly Active Engineered Cartilage: in vivo Comparative Assessment |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180110 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180110 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20180925 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20181207 |
|
| 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: 20190205 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20190307 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6495934 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |