CA2760768C - Modele de tissu pulmonaire - Google Patents
Modele de tissu pulmonaire Download PDFInfo
- Publication number
- CA2760768C CA2760768C CA2760768A CA2760768A CA2760768C CA 2760768 C CA2760768 C CA 2760768C CA 2760768 A CA2760768 A CA 2760768A CA 2760768 A CA2760768 A CA 2760768A CA 2760768 C CA2760768 C CA 2760768C
- Authority
- CA
- Canada
- Prior art keywords
- cells
- pulmonary
- tissue culture
- model
- dimensional
- 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
- 210000004072 lung Anatomy 0.000 title claims abstract description 100
- 238000013334 tissue model Methods 0.000 title description 21
- 230000002685 pulmonary effect Effects 0.000 claims abstract description 140
- 238000012360 testing method Methods 0.000 claims abstract description 53
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 45
- 201000010099 disease Diseases 0.000 claims abstract description 44
- 239000002407 tissue scaffold Substances 0.000 claims abstract description 34
- 229940079593 drug Drugs 0.000 claims abstract description 32
- 239000003814 drug Substances 0.000 claims abstract description 32
- 230000000694 effects Effects 0.000 claims abstract description 17
- 238000012216 screening Methods 0.000 claims abstract description 12
- 208000019693 Lung disease Diseases 0.000 claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 9
- 210000004027 cell Anatomy 0.000 claims description 390
- 210000001519 tissue Anatomy 0.000 claims description 284
- 210000002950 fibroblast Anatomy 0.000 claims description 82
- 210000002919 epithelial cell Anatomy 0.000 claims description 80
- 230000014509 gene expression Effects 0.000 claims description 73
- 238000000034 method Methods 0.000 claims description 60
- 102000004127 Cytokines Human genes 0.000 claims description 34
- 108090000695 Cytokines Proteins 0.000 claims description 34
- 239000000523 sample Substances 0.000 claims description 33
- 230000001413 cellular effect Effects 0.000 claims description 30
- 230000001965 increasing effect Effects 0.000 claims description 30
- 239000013074 reference sample Substances 0.000 claims description 29
- 206010028980 Neoplasm Diseases 0.000 claims description 26
- 210000002383 alveolar type I cell Anatomy 0.000 claims description 24
- 238000002360 preparation method Methods 0.000 claims description 24
- 108090000991 Aquaporin 3 Proteins 0.000 claims description 23
- 238000012258 culturing Methods 0.000 claims description 22
- 239000011159 matrix material Substances 0.000 claims description 22
- 102000004363 Aquaporin 3 Human genes 0.000 claims description 21
- 210000002889 endothelial cell Anatomy 0.000 claims description 21
- 102000007615 Pulmonary Surfactant-Associated Protein A Human genes 0.000 claims description 20
- 108010007100 Pulmonary Surfactant-Associated Protein A Proteins 0.000 claims description 20
- 230000000770 proinflammatory effect Effects 0.000 claims description 20
- 108090001005 Interleukin-6 Proteins 0.000 claims description 19
- 102100023974 Keratin, type II cytoskeletal 7 Human genes 0.000 claims description 18
- 239000000725 suspension Substances 0.000 claims description 18
- 102100027893 Homeobox protein Nkx-2.1 Human genes 0.000 claims description 17
- 101000632178 Homo sapiens Homeobox protein Nkx-2.1 Proteins 0.000 claims description 17
- 230000003247 decreasing effect Effects 0.000 claims description 17
- 230000002757 inflammatory effect Effects 0.000 claims description 17
- 101000845269 Homo sapiens Transcription termination factor 1 Proteins 0.000 claims description 16
- 206010061218 Inflammation Diseases 0.000 claims description 16
- 230000004054 inflammatory process Effects 0.000 claims description 16
- 101000975502 Homo sapiens Keratin, type II cytoskeletal 7 Proteins 0.000 claims description 15
- 101000612671 Homo sapiens Pulmonary surfactant-associated protein C Proteins 0.000 claims description 15
- 108010085149 S100 Calcium-Binding Protein A4 Proteins 0.000 claims description 15
- 230000015572 biosynthetic process Effects 0.000 claims description 15
- 102100040971 Pulmonary surfactant-associated protein C Human genes 0.000 claims description 14
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 claims description 13
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 claims description 13
- 230000004048 modification Effects 0.000 claims description 13
- 238000012986 modification Methods 0.000 claims description 13
- 102000000905 Cadherin Human genes 0.000 claims description 12
- 108050007957 Cadherin Proteins 0.000 claims description 12
- 230000009786 epithelial differentiation Effects 0.000 claims description 12
- 206010016654 Fibrosis Diseases 0.000 claims description 11
- 230000004075 alteration Effects 0.000 claims description 11
- 210000004748 cultured cell Anatomy 0.000 claims description 11
- 230000004761 fibrosis Effects 0.000 claims description 11
- 210000004879 pulmonary tissue Anatomy 0.000 claims description 11
- 230000008614 cellular interaction Effects 0.000 claims description 10
- 230000006378 damage Effects 0.000 claims description 10
- 210000002744 extracellular matrix Anatomy 0.000 claims description 10
- 239000002609 medium Substances 0.000 claims description 9
- 239000012528 membrane Substances 0.000 claims description 9
- 230000001575 pathological effect Effects 0.000 claims description 9
- 101001055222 Homo sapiens Interleukin-8 Proteins 0.000 claims description 8
- 102100026236 Interleukin-8 Human genes 0.000 claims description 8
- 239000012298 atmosphere Substances 0.000 claims description 8
- 230000009286 beneficial effect Effects 0.000 claims description 8
- 108050000637 N-cadherin Proteins 0.000 claims description 7
- 208000027418 Wounds and injury Diseases 0.000 claims description 6
- 239000006285 cell suspension Substances 0.000 claims description 6
- 208000014674 injury Diseases 0.000 claims description 6
- 238000003556 assay Methods 0.000 claims description 5
- 230000008929 regeneration Effects 0.000 claims description 5
- 238000011069 regeneration method Methods 0.000 claims description 5
- -1 IL1b Proteins 0.000 claims description 4
- 108010070507 Keratin-7 Proteins 0.000 claims description 4
- 230000002411 adverse Effects 0.000 claims description 4
- 230000002068 genetic effect Effects 0.000 claims description 4
- 230000009466 transformation Effects 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 claims description 3
- 230000006907 apoptotic process Effects 0.000 claims description 2
- 230000003833 cell viability Effects 0.000 claims description 2
- 230000001627 detrimental effect Effects 0.000 claims description 2
- 231100000331 toxic Toxicity 0.000 claims description 2
- 230000002588 toxic effect Effects 0.000 claims description 2
- 238000011160 research Methods 0.000 abstract description 12
- 238000003491 array Methods 0.000 abstract description 3
- 241000282414 Homo sapiens Species 0.000 description 43
- 108090000623 proteins and genes Proteins 0.000 description 42
- 108020004414 DNA Proteins 0.000 description 27
- 238000004113 cell culture Methods 0.000 description 26
- 238000003501 co-culture Methods 0.000 description 24
- 108020004999 messenger RNA Proteins 0.000 description 24
- 230000004069 differentiation Effects 0.000 description 22
- 239000000203 mixture Substances 0.000 description 21
- 238000002474 experimental method Methods 0.000 description 20
- 210000002821 alveolar epithelial cell Anatomy 0.000 description 18
- 239000000463 material Substances 0.000 description 18
- 102000004169 proteins and genes Human genes 0.000 description 17
- 210000002588 alveolar type II cell Anatomy 0.000 description 16
- 230000002441 reversible effect Effects 0.000 description 15
- 238000011161 development Methods 0.000 description 14
- 230000018109 developmental process Effects 0.000 description 14
- 210000005265 lung cell Anatomy 0.000 description 14
- 102100023087 Protein S100-A4 Human genes 0.000 description 13
- 230000007705 epithelial mesenchymal transition Effects 0.000 description 12
- 239000003550 marker Substances 0.000 description 11
- 230000008569 process Effects 0.000 description 11
- 238000005204 segregation Methods 0.000 description 11
- 239000010410 layer Substances 0.000 description 10
- 210000002540 macrophage Anatomy 0.000 description 10
- 108010082117 matrigel Proteins 0.000 description 10
- 238000009343 monoculture Methods 0.000 description 10
- 239000000975 dye Substances 0.000 description 9
- 210000000981 epithelium Anatomy 0.000 description 9
- 230000011664 signaling Effects 0.000 description 9
- 102000004392 Aquaporin 5 Human genes 0.000 description 8
- 108090000976 Aquaporin 5 Proteins 0.000 description 8
- 101710114425 Homeobox protein Nkx-2.1 Proteins 0.000 description 8
- 101710088547 Thyroid transcription factor 1 Proteins 0.000 description 8
- 101710159262 Transcription termination factor 1 Proteins 0.000 description 8
- 239000000853 adhesive Substances 0.000 description 8
- 230000001070 adhesive effect Effects 0.000 description 8
- 239000003102 growth factor Substances 0.000 description 8
- 210000003630 histaminocyte Anatomy 0.000 description 8
- 238000011534 incubation Methods 0.000 description 8
- 208000020816 lung neoplasm Diseases 0.000 description 8
- 208000037841 lung tumor Diseases 0.000 description 8
- 210000004379 membrane Anatomy 0.000 description 8
- 210000000056 organ Anatomy 0.000 description 8
- 102000026633 IL6 Human genes 0.000 description 7
- 230000003993 interaction Effects 0.000 description 7
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 7
- 108010036280 Aquaporin 4 Proteins 0.000 description 6
- 102100037276 Aquaporin-4 Human genes 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 108700039887 Essential Genes Proteins 0.000 description 6
- 101001086862 Homo sapiens Pulmonary surfactant-associated protein B Proteins 0.000 description 6
- 230000032459 dedifferentiation Effects 0.000 description 6
- 238000001476 gene delivery Methods 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 230000008611 intercellular interaction Effects 0.000 description 6
- 230000003278 mimic effect Effects 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 230000001105 regulatory effect Effects 0.000 description 6
- 230000008439 repair process Effects 0.000 description 6
- 210000000130 stem cell Anatomy 0.000 description 6
- 210000004881 tumor cell Anatomy 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 208000012868 Overgrowth Diseases 0.000 description 5
- 102100032617 Pulmonary surfactant-associated protein B Human genes 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 230000007040 lung development Effects 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 238000001338 self-assembly Methods 0.000 description 5
- 239000004094 surface-active agent Substances 0.000 description 5
- 239000013598 vector Substances 0.000 description 5
- 238000012604 3D cell culture Methods 0.000 description 4
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 4
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 4
- 102100023600 Fibroblast growth factor receptor 2 Human genes 0.000 description 4
- 101710182389 Fibroblast growth factor receptor 2 Proteins 0.000 description 4
- 101000864780 Homo sapiens Pulmonary surfactant-associated protein A1 Proteins 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 102100030060 Pulmonary surfactant-associated protein A1 Human genes 0.000 description 4
- 210000001744 T-lymphocyte Anatomy 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000012228 culture supernatant Substances 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 230000003511 endothelial effect Effects 0.000 description 4
- 230000001605 fetal effect Effects 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 210000005260 human cell Anatomy 0.000 description 4
- 238000010874 in vitro model Methods 0.000 description 4
- 210000004924 lung microvascular endothelial cell Anatomy 0.000 description 4
- 230000036961 partial effect Effects 0.000 description 4
- 239000008188 pellet Substances 0.000 description 4
- 238000003753 real-time PCR Methods 0.000 description 4
- 238000003757 reverse transcription PCR Methods 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 230000002269 spontaneous effect Effects 0.000 description 4
- 230000001960 triggered effect Effects 0.000 description 4
- 241000701161 unidentified adenovirus Species 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 102000007469 Actins Human genes 0.000 description 3
- 108010085238 Actins Proteins 0.000 description 3
- 108010078791 Carrier Proteins Proteins 0.000 description 3
- 101100264065 Danio rerio wnt5b gene Proteins 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- 102100028412 Fibroblast growth factor 10 Human genes 0.000 description 3
- 108090001047 Fibroblast growth factor 10 Proteins 0.000 description 3
- 102000004890 Interleukin-8 Human genes 0.000 description 3
- 108090001007 Interleukin-8 Proteins 0.000 description 3
- 238000011529 RT qPCR Methods 0.000 description 3
- 102000013814 Wnt Human genes 0.000 description 3
- 108050003627 Wnt Proteins 0.000 description 3
- 239000000560 biocompatible material Substances 0.000 description 3
- 210000001185 bone marrow Anatomy 0.000 description 3
- 210000000481 breast Anatomy 0.000 description 3
- 239000006143 cell culture medium Substances 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 238000004624 confocal microscopy Methods 0.000 description 3
- 239000003596 drug target Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000007850 fluorescent dye Substances 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 238000013537 high throughput screening Methods 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 210000004969 inflammatory cell Anatomy 0.000 description 3
- 230000004968 inflammatory condition Effects 0.000 description 3
- 238000002372 labelling Methods 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 230000035479 physiological effects, processes and functions Effects 0.000 description 3
- 210000004043 pneumocyte Anatomy 0.000 description 3
- 230000001855 preneoplastic effect Effects 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 208000005069 pulmonary fibrosis Diseases 0.000 description 3
- 108700042226 ras Genes Proteins 0.000 description 3
- 230000000241 respiratory effect Effects 0.000 description 3
- 239000002356 single layer Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- 238000012605 2D cell culture Methods 0.000 description 2
- 238000013296 A/J mouse Methods 0.000 description 2
- 102100037332 Aquaporin-3 Human genes 0.000 description 2
- 102000010637 Aquaporins Human genes 0.000 description 2
- 108010063290 Aquaporins Proteins 0.000 description 2
- 241000271566 Aves Species 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 102000019034 Chemokines Human genes 0.000 description 2
- 108010012236 Chemokines Proteins 0.000 description 2
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 2
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 2
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 2
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 2
- 102000014429 Insulin-like growth factor Human genes 0.000 description 2
- 108090000174 Interleukin-10 Proteins 0.000 description 2
- 102000003814 Interleukin-10 Human genes 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 2
- 101150040459 RAS gene Proteins 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 108010057966 Thyroid Nuclear Factor 1 Proteins 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102100040247 Tumor necrosis factor Human genes 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 210000001552 airway epithelial cell Anatomy 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 208000030270 breast disease Diseases 0.000 description 2
- 230000011712 cell development Effects 0.000 description 2
- 230000009087 cell motility Effects 0.000 description 2
- 210000002421 cell wall Anatomy 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 210000001608 connective tissue cell Anatomy 0.000 description 2
- 230000030944 contact inhibition Effects 0.000 description 2
- 230000016396 cytokine production Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 229940000406 drug candidate Drugs 0.000 description 2
- 238000003255 drug test Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 210000002782 epithelial mesenchymal cell Anatomy 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 238000010353 genetic engineering Methods 0.000 description 2
- 210000003714 granulocyte Anatomy 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 239000000017 hydrogel Substances 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000007905 lung morphogenesis Effects 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- 239000012982 microporous membrane Substances 0.000 description 2
- 210000004925 microvascular endothelial cell Anatomy 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 239000003068 molecular probe Substances 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 230000000921 morphogenic effect Effects 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000008521 reorganization Effects 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 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 2
- 231100000041 toxicology testing Toxicity 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 210000005166 vasculature Anatomy 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- 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 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 108020004463 18S ribosomal RNA Proteins 0.000 description 1
- UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 1
- 238000013335 3D tissue model Methods 0.000 description 1
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 1
- 206010001258 Adenoviral infections Diseases 0.000 description 1
- 240000000662 Anethum graveolens Species 0.000 description 1
- 101100492780 Arabidopsis thaliana ATI1 gene Proteins 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101150071146 COX2 gene Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 102000011727 Caspases Human genes 0.000 description 1
- 108010076667 Caspases Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 102000003858 Chymases Human genes 0.000 description 1
- 108090000227 Chymases Proteins 0.000 description 1
- 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 description 1
- 102100031614 Ciliary neurotrophic factor Human genes 0.000 description 1
- 102000016911 Deoxyribonucleases Human genes 0.000 description 1
- 108010053770 Deoxyribonucleases Proteins 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 108700025781 Drosophila bnl Proteins 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108091008794 FGF receptors Proteins 0.000 description 1
- 101150099234 FGF10 gene Proteins 0.000 description 1
- 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 1
- 102100028072 Fibroblast growth factor 4 Human genes 0.000 description 1
- 102100028071 Fibroblast growth factor 7 Human genes 0.000 description 1
- 102100037680 Fibroblast growth factor 8 Human genes 0.000 description 1
- 102100037665 Fibroblast growth factor 9 Human genes 0.000 description 1
- 101150066002 GFP gene Proteins 0.000 description 1
- 101710113436 GTPase KRas Proteins 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000806690 Homo sapiens Aquaporin-3 Proteins 0.000 description 1
- 101000806663 Homo sapiens Aquaporin-4 Proteins 0.000 description 1
- 101000984015 Homo sapiens Cadherin-1 Proteins 0.000 description 1
- 101001060274 Homo sapiens Fibroblast growth factor 4 Proteins 0.000 description 1
- 101001060261 Homo sapiens Fibroblast growth factor 7 Proteins 0.000 description 1
- 101001027382 Homo sapiens Fibroblast growth factor 8 Proteins 0.000 description 1
- 101001027380 Homo sapiens Fibroblast growth factor 9 Proteins 0.000 description 1
- 101000998146 Homo sapiens Interleukin-17A Proteins 0.000 description 1
- 101000685724 Homo sapiens Protein S100-A4 Proteins 0.000 description 1
- 101000804792 Homo sapiens Protein Wnt-5a Proteins 0.000 description 1
- 101000595467 Homo sapiens T-complex protein 1 subunit gamma Proteins 0.000 description 1
- 241000700588 Human alphaherpesvirus 1 Species 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 101150093590 IJ gene Proteins 0.000 description 1
- 108091058560 IL8 Proteins 0.000 description 1
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 1
- 108010034143 Inflammasomes Proteins 0.000 description 1
- 240000004759 Inga spectabilis Species 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102000003815 Interleukin-11 Human genes 0.000 description 1
- 108090000177 Interleukin-11 Proteins 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 102000013462 Interleukin-12 Human genes 0.000 description 1
- 108090000176 Interleukin-13 Proteins 0.000 description 1
- 102000003816 Interleukin-13 Human genes 0.000 description 1
- 101800003050 Interleukin-16 Proteins 0.000 description 1
- 102000049772 Interleukin-16 Human genes 0.000 description 1
- 102100033461 Interleukin-17A Human genes 0.000 description 1
- 102000003810 Interleukin-18 Human genes 0.000 description 1
- 108090000171 Interleukin-18 Proteins 0.000 description 1
- 102000004388 Interleukin-4 Human genes 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 108010044467 Isoenzymes Proteins 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- 239000012097 Lipofectamine 2000 Substances 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- 108010006035 Metalloproteases Proteins 0.000 description 1
- 102100025748 Mothers against decapentaplegic homolog 3 Human genes 0.000 description 1
- 101710143111 Mothers against decapentaplegic homolog 3 Proteins 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101001027368 Mus musculus Fibroblast growth factor 9 Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010028311 Muscle hypertrophy Diseases 0.000 description 1
- 101150111110 NKX2-1 gene Proteins 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 108090000630 Oncostatin M Proteins 0.000 description 1
- 102100031942 Oncostatin-M Human genes 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 208000001300 Perinatal Death Diseases 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
- 239000013614 RNA sample Substances 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 238000010240 RT-PCR analysis Methods 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 102100036049 T-complex protein 1 subunit gamma Human genes 0.000 description 1
- 108091005735 TGF-beta receptors Proteins 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 102000016715 Transforming Growth Factor beta Receptors Human genes 0.000 description 1
- 102000001400 Tryptase Human genes 0.000 description 1
- 108060005989 Tryptase Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 102000043366 Wnt-5a Human genes 0.000 description 1
- 210000002718 aborted fetus Anatomy 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 230000008649 adaptation response Effects 0.000 description 1
- 210000000677 aggregate cell Anatomy 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000019552 anatomical structure morphogenesis Effects 0.000 description 1
- 210000000648 angioblast Anatomy 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 238000010256 biochemical assay Methods 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004979 bone marrow derived macrophage Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000000424 bronchial epithelial cell Anatomy 0.000 description 1
- 208000003362 bronchogenic carcinoma Diseases 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 208000002458 carcinoid tumor Diseases 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000002975 chemoattractant Substances 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 210000004081 cilia Anatomy 0.000 description 1
- 229940121657 clinical drug Drugs 0.000 description 1
- 239000000512 collagen gel Substances 0.000 description 1
- 238000005094 computer simulation Methods 0.000 description 1
- 238000010226 confocal imaging Methods 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 210000000555 contractile cell Anatomy 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 150000002066 eicosanoids Chemical class 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 230000010393 epithelial cell migration Effects 0.000 description 1
- 230000008472 epithelial growth Effects 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 229940126864 fibroblast growth factor Drugs 0.000 description 1
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 238000012239 gene modification Methods 0.000 description 1
- 230000005017 genetic modification Effects 0.000 description 1
- 235000013617 genetically modified food Nutrition 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 210000003566 hemangioblast Anatomy 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 102000054990 human NKX2-1 Human genes 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 238000010324 immunological assay Methods 0.000 description 1
- 230000004957 immunoregulator effect Effects 0.000 description 1
- 238000012606 in vitro cell culture Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 210000004692 intercellular junction Anatomy 0.000 description 1
- 210000003963 intermediate filament Anatomy 0.000 description 1
- 208000036971 interstitial lung disease 2 Diseases 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000006517 limb development Effects 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 201000005249 lung adenocarcinoma Diseases 0.000 description 1
- 230000011360 lung alveolus development Effects 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 239000003580 lung surfactant Substances 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 238000010841 mRNA extraction Methods 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 208000011645 metastatic carcinoma Diseases 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 229960002900 methylcellulose Drugs 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 230000005486 microgravity Effects 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 210000000110 microvilli Anatomy 0.000 description 1
- 239000003147 molecular marker Substances 0.000 description 1
- 238000004264 monolayer culture Methods 0.000 description 1
- 230000024799 morphogenesis of a branching structure Effects 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 238000011206 morphological examination Methods 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 230000012042 muscle hypertrophy Effects 0.000 description 1
- 239000003471 mutagenic agent Substances 0.000 description 1
- 231100000707 mutagenic chemical Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 210000000651 myofibroblast Anatomy 0.000 description 1
- 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 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000003227 neuromodulating effect Effects 0.000 description 1
- 230000001473 noxious effect Effects 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000005305 organ development Effects 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 239000013610 patient sample Substances 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 238000011338 personalized therapy Methods 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000006013 primary lung bud formation Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 210000003456 pulmonary alveoli Anatomy 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 239000003642 reactive oxygen metabolite Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000009283 reversible contraction Effects 0.000 description 1
- 238000009781 safety test method Methods 0.000 description 1
- 238000003118 sandwich ELISA Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 210000004739 secretory vesicle Anatomy 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 239000013605 shuttle vector Substances 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000002490 spark plasma sintering Methods 0.000 description 1
- 210000004085 squamous epithelial cell Anatomy 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000007801 sublethal irradiation Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000002344 surface layer Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 230000002992 thymic effect Effects 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 210000001578 tight junction Anatomy 0.000 description 1
- 239000003104 tissue culture media Substances 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000005740 tumor formation Effects 0.000 description 1
- 230000000381 tumorigenic effect Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 230000004222 uncontrolled growth Effects 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 230000006442 vascular tone Effects 0.000 description 1
- 230000004862 vasculogenesis Effects 0.000 description 1
- 230000002227 vasoactive effect Effects 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 230000017613 viral reproduction Effects 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5082—Supracellular entities, e.g. tissue, organisms
- G01N33/5088—Supracellular entities, e.g. tissue, organisms of vertebrates
-
- 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
- C12N5/0688—Cells from the lungs or the respiratory tract
-
- 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
- C12N2500/00—Specific components of cell culture medium
- C12N2500/02—Atmosphere, e.g. low oxygen conditions
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/13—Coculture with; Conditioned medium produced by connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic fibroblasts"
- C12N2502/1323—Adult fibroblasts
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/28—Vascular endothelial cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2503/00—Use of cells in diagnostics
- C12N2503/04—Screening or testing on artificial tissues
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Microbiology (AREA)
- Organic Chemistry (AREA)
- Urology & Nephrology (AREA)
- Biochemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Tropical Medicine & Parasitology (AREA)
- Food Science & Technology (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Pulmonology (AREA)
- Physics & Mathematics (AREA)
- Medicinal Chemistry (AREA)
- Analytical Chemistry (AREA)
- General Engineering & Computer Science (AREA)
- Toxicology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
L'invention concerne une culture tissulaire d'un modèle pulmonaire tridimensionnel dépourvu de structure tissulaire mise au point par génie tissulaire, qui est exempte de toute structure artificielle; des modèles tridimensionnels de tissu pulmonaire sain ainsi que des tissus pathologiques. Le produit de l'invention peut être commercialisé, p. ex. sous la forme de cultures tissulaires, de plaques ou de réseaux comprenant ces cultures ou de trousses. L'invention peut être appliquée dans la recherche médicale et scientifique pour tester l'effet de composés sur un tissu pulmonaire, à des fins de criblage, d'essai et/ou d'évaluation de médicaments, et dans certains cas pour diagnostiquer des maladies pulmonaires.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
HUP0900819 | 2009-05-05 | ||
HU0900819A HUP0900819A2 (en) | 2009-05-05 | 2009-05-05 | Lung tissue culture |
PCT/IB2010/051978 WO2010128464A1 (fr) | 2009-05-05 | 2010-05-05 | Modèle de tissu pulmonaire |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2760768A1 CA2760768A1 (fr) | 2010-11-11 |
CA2760768C true CA2760768C (fr) | 2019-10-29 |
Family
ID=89989476
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA2760768A Active CA2760768C (fr) | 2009-05-05 | 2010-05-05 | Modele de tissu pulmonaire |
Country Status (7)
Country | Link |
---|---|
JP (1) | JP2013504303A (fr) |
CN (1) | CN102369277B (fr) |
AU (1) | AU2010244121B2 (fr) |
CA (1) | CA2760768C (fr) |
HU (1) | HUP0900819A2 (fr) |
SG (1) | SG175425A1 (fr) |
WO (1) | WO2010128464A1 (fr) |
Families Citing this family (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
HUE029316T2 (en) | 2010-11-04 | 2017-03-28 | Univ Of Pecs | Tüdõszövetmodell |
JP5778412B2 (ja) * | 2010-11-29 | 2015-09-16 | 花王株式会社 | Cgrp応答調節剤の評価又は選択方法 |
TWI438145B (zh) * | 2011-12-08 | 2014-05-21 | 中原大學 | 連續式產氫裝置及其方法 |
US20140099709A1 (en) * | 2012-06-19 | 2014-04-10 | Organovo, Inc. | Engineered three-dimensional connective tissue constructs and methods of making the same |
JP6463275B2 (ja) * | 2013-01-08 | 2019-01-30 | イエール ユニバーシティ | ヒトおよび大型哺乳動物の肺のバイオリアクター |
WO2015061372A1 (fr) | 2013-10-21 | 2015-04-30 | Hemoshear, Llc | Modèle in vitro pour micro-environnement tumoral |
CN104316661B (zh) * | 2014-10-08 | 2016-03-23 | 清华大学 | 用于生物毒性检测的肺组织模型及生物毒性检测方法 |
CA2972226A1 (fr) * | 2014-12-24 | 2016-06-30 | Ube Industries, Ltd. | Fluide de surnageant de culture de cellules derive de tissu pulmonaire |
US20190128870A1 (en) * | 2016-04-04 | 2019-05-02 | Humeltis | Diagnostic Methods For Patient Specific Therapeutic Decision Making In Cancer Care |
CN106754669B (zh) * | 2016-11-23 | 2020-04-17 | 河海大学常州校区 | 基于反应-扩散模型的多细胞结构的制备方法及制备系统 |
CN107267439A (zh) * | 2017-05-16 | 2017-10-20 | 苏州大学 | 三维肺微组织模型的构建方法及应用 |
CN108660076A (zh) * | 2018-05-21 | 2018-10-16 | 中国科学院苏州生物医学工程技术研究所 | 一种仿真肺芯片模型 |
CN109161531A (zh) * | 2018-10-16 | 2019-01-08 | 首都医科大学附属北京胸科医院 | 一种基于类器官技术个体化肺癌原代细胞培养的方法 |
GB202005154D0 (en) * | 2020-04-07 | 2020-05-20 | Univ Of Hertfordshire Higher Education Corporation | Method and model |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6828111B2 (en) * | 2000-01-13 | 2004-12-07 | Wayne State University | Three-dimensional in vitro model of human preneoplastic breast disease |
WO2003010302A1 (fr) * | 2001-07-26 | 2003-02-06 | Kazunori Kataoka | Construction cellulaire cultivee contenant des spheroides de cellules animales cultivees et utilisation correspondante |
WO2007083504A1 (fr) * | 2003-08-01 | 2007-07-26 | Norimasa Nakamura | Tissu synthétique en 3d auto-organisé sans échafaudage |
US7709256B2 (en) * | 2004-04-28 | 2010-05-04 | Vaxdesign Corp. | Disease model incorporation into an artificial immune system (AIS) |
US8628964B2 (en) * | 2006-10-11 | 2014-01-14 | Drexel University | Fetal pulmonary cells and uses thereof |
US20100034791A1 (en) * | 2007-02-14 | 2010-02-11 | Drexel University | Engineered Lung Tissue Construction for High Throughput Toxicity Screening and Drug Discovery |
-
2009
- 2009-05-05 HU HU0900819A patent/HUP0900819A2/hu unknown
-
2010
- 2010-05-05 AU AU2010244121A patent/AU2010244121B2/en not_active Ceased
- 2010-05-05 CN CN201080020612.7A patent/CN102369277B/zh not_active Expired - Fee Related
- 2010-05-05 WO PCT/IB2010/051978 patent/WO2010128464A1/fr active Application Filing
- 2010-05-05 JP JP2012509145A patent/JP2013504303A/ja active Pending
- 2010-05-05 SG SG2011080223A patent/SG175425A1/en unknown
- 2010-05-05 CA CA2760768A patent/CA2760768C/fr active Active
Also Published As
Publication number | Publication date |
---|---|
WO2010128464A1 (fr) | 2010-11-11 |
CN102369277B (zh) | 2014-12-17 |
SG175425A1 (en) | 2011-12-29 |
CN102369277A (zh) | 2012-03-07 |
AU2010244121B2 (en) | 2015-07-16 |
HUP0900819A2 (en) | 2011-01-28 |
JP2013504303A (ja) | 2013-02-07 |
CA2760768A1 (fr) | 2010-11-11 |
AU2010244121A1 (en) | 2011-12-15 |
HU0900819D0 (en) | 2010-07-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CA2760768C (fr) | Modele de tissu pulmonaire | |
US9151744B2 (en) | Lung tissue model | |
JP2021508249A (ja) | 免疫細胞オルガノイド共培養物 | |
Choi et al. | Organogenesis of adult lung in a dish: Differentiation, disease and therapy | |
EP3699275A1 (fr) | Organoïde d'organe et procédé de production associé | |
JP2018506971A (ja) | 胃腸上皮組織構築物を生成する方法 ナンシー・オールブリトン(Nancy Allbritton)、ユリ・ワン(Yuli Wang)、クリストファー・シムズ(Christopher Sims)、スコット・マグネス(Scott Magness)及びスコット・ブルトマン(Scott Bultman) | |
JP2017524377A (ja) | 単一細胞由来オルガノイド | |
ES2664375T3 (es) | Precursores de células estrelladas hepáticas y métodos para aislarlos | |
TW202039828A (zh) | 肝細胞擴增方法 | |
Cao et al. | Understanding the role of the microenvironment during definitive hemopoietic development | |
TW202200786A (zh) | 自肺上皮細胞或肺癌細胞製造類器官之方法 | |
CN111876371A (zh) | 心脏细胞培养材料 | |
Clause et al. | A Three-Dimensional Gel Bioreactor for Assessment of Cardiomyocyte Induction in Skeletal Muscle–Derived Stem Cells | |
JP7274683B2 (ja) | 多能性幹細胞から樹状分岐した集合管を伴う腎臓構造を作製する方法 | |
US9687512B2 (en) | Isolated cardiac stem cells and methods of their use | |
EP3927814A1 (fr) | Procédés pour la maturation de cardiomyocytes sur des ecm dérivées de cellules de luquide amniotique, constructions cellulaires et utilisations pour la cardiotoxicité et le criblage proarythmique de composés médicamenteux | |
JP2008206510A (ja) | 腸管幹/前駆細胞の取得方法 | |
Perugini et al. | A Substrate-Mimicking Basement Membrane Drives the Organization of Human Mesenchymal Stromal Cells and Endothelial Cells Into Perivascular Niche-Like Structures | |
JP7576647B2 (ja) | 肝臓オルガノイド疾患モデルおよびその作製方法 | |
Ochiai et al. | Posology and Serum-/Xeno-Free Engineered Adipose Stromal Cells Cell Sheets | |
Forghani | Fabrication of a Quasi-3D Vascularized Bone Like Construct | |
TW202417612A (zh) | 非真皮乳突細胞至真皮乳突細胞之轉分化(transdifferentiation) | |
CN114317398A (zh) | Gli1和EpCAM基因共同标记的肝祖细胞群及其应用 | |
Costa | Adipose stromal vascular fraction cell sheets as vascular strategies for tissue engineering and regenerative medicine applications | |
Costea | Epithelial-mesenchymal interactions in normal and neoplastic human oral mucosa. A study on in vitro organotypic models |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
EEER | Examination request |
Effective date: 20150501 |