JP2010528055A - 慢性肺疾患の治療 - Google Patents
慢性肺疾患の治療 Download PDFInfo
- Publication number
- JP2010528055A JP2010528055A JP2010509623A JP2010509623A JP2010528055A JP 2010528055 A JP2010528055 A JP 2010528055A JP 2010509623 A JP2010509623 A JP 2010509623A JP 2010509623 A JP2010509623 A JP 2010509623A JP 2010528055 A JP2010528055 A JP 2010528055A
- Authority
- JP
- Japan
- Prior art keywords
- aec
- lung
- haec
- subject
- stem cells
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 208000019693 Lung disease Diseases 0.000 title claims abstract description 42
- 230000001684 chronic effect Effects 0.000 title abstract description 12
- 238000011282 treatment Methods 0.000 title description 19
- 210000004072 lung Anatomy 0.000 claims abstract description 72
- 238000000034 method Methods 0.000 claims abstract description 57
- 208000004852 Lung Injury Diseases 0.000 claims abstract description 26
- 206010069363 Traumatic lung injury Diseases 0.000 claims abstract description 26
- 231100000515 lung injury Toxicity 0.000 claims abstract description 26
- 208000024891 symptom Diseases 0.000 claims abstract description 23
- 238000002659 cell therapy Methods 0.000 claims abstract description 16
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims abstract description 15
- 210000001691 amnion Anatomy 0.000 claims abstract description 12
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims abstract description 8
- 210000000817 amniotic epithelial stem cell Anatomy 0.000 claims description 85
- 102000008186 Collagen Human genes 0.000 claims description 26
- 108010035532 Collagen Proteins 0.000 claims description 26
- 229920001436 collagen Polymers 0.000 claims description 26
- 206010035664 Pneumonia Diseases 0.000 claims description 16
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 16
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 15
- 210000002826 placenta Anatomy 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 13
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 10
- 208000036971 interstitial lung disease 2 Diseases 0.000 claims description 10
- 239000004094 surface-active agent Substances 0.000 claims description 10
- 101100257359 Caenorhabditis elegans sox-2 gene Proteins 0.000 claims description 9
- 101100257363 Mus musculus Sox2 gene Proteins 0.000 claims description 9
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 9
- 241001465754 Metazoa Species 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 230000002685 pulmonary effect Effects 0.000 claims description 8
- 206010069351 acute lung injury Diseases 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 230000001605 fetal effect Effects 0.000 claims description 6
- 231100000167 toxic agent Toxicity 0.000 claims description 5
- 238000002512 chemotherapy Methods 0.000 claims description 4
- 208000035475 disorder Diseases 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 238000001959 radiotherapy Methods 0.000 claims description 4
- 231100000331 toxic Toxicity 0.000 claims description 4
- 230000002588 toxic effect Effects 0.000 claims description 4
- 208000019462 Occupational injury Diseases 0.000 claims 2
- 239000011859 microparticle Substances 0.000 claims 2
- 230000029058 respiratory gaseous exchange Effects 0.000 claims 2
- 239000003440 toxic substance Substances 0.000 claims 1
- 210000000130 stem cell Anatomy 0.000 abstract description 14
- 230000000241 respiratory effect Effects 0.000 abstract description 6
- 230000001154 acute effect Effects 0.000 abstract description 4
- 210000004027 cell Anatomy 0.000 description 63
- 108010006654 Bleomycin Proteins 0.000 description 54
- 229960001561 bleomycin Drugs 0.000 description 53
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 53
- 241000699670 Mus sp. Species 0.000 description 33
- 230000004761 fibrosis Effects 0.000 description 29
- 206010016654 Fibrosis Diseases 0.000 description 25
- 210000001519 tissue Anatomy 0.000 description 25
- 230000001965 increasing effect Effects 0.000 description 18
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 17
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 17
- 102100040971 Pulmonary surfactant-associated protein C Human genes 0.000 description 15
- 101000612671 Homo sapiens Pulmonary surfactant-associated protein C Proteins 0.000 description 14
- 230000000694 effects Effects 0.000 description 13
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 12
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 12
- 230000008021 deposition Effects 0.000 description 12
- 102000000589 Interleukin-1 Human genes 0.000 description 11
- 108010002352 Interleukin-1 Proteins 0.000 description 11
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 11
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 11
- 210000002588 alveolar type II cell Anatomy 0.000 description 11
- 210000002540 macrophage Anatomy 0.000 description 11
- 108090000623 proteins and genes Proteins 0.000 description 11
- 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 10
- 102000004889 Interleukin-6 Human genes 0.000 description 10
- 108090001005 Interleukin-6 Proteins 0.000 description 10
- 102100035423 POU domain, class 5, transcription factor 1 Human genes 0.000 description 10
- 101710126211 POU domain, class 5, transcription factor 1 Proteins 0.000 description 10
- 230000004069 differentiation Effects 0.000 description 10
- 210000002950 fibroblast Anatomy 0.000 description 10
- 230000004054 inflammatory process Effects 0.000 description 10
- 239000003112 inhibitor Substances 0.000 description 10
- 229940100601 interleukin-6 Drugs 0.000 description 10
- 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 10
- 102000004127 Cytokines Human genes 0.000 description 9
- 108090000695 Cytokines Proteins 0.000 description 9
- 206010061218 Inflammation Diseases 0.000 description 9
- 230000006378 damage Effects 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 229940090044 injection Drugs 0.000 description 9
- 239000007924 injection Substances 0.000 description 9
- 238000002347 injection Methods 0.000 description 9
- 239000003550 marker Substances 0.000 description 9
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 8
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 238000003753 real-time PCR Methods 0.000 description 8
- 230000008439 repair process Effects 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- 102100026802 72 kDa type IV collagenase Human genes 0.000 description 7
- 101710151806 72 kDa type IV collagenase Proteins 0.000 description 7
- 108010074328 Interferon-gamma Proteins 0.000 description 7
- 102000000588 Interleukin-2 Human genes 0.000 description 7
- 108010002350 Interleukin-2 Proteins 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- 210000002919 epithelial cell Anatomy 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 102000009571 Macrophage Inflammatory Proteins Human genes 0.000 description 6
- 108010009474 Macrophage Inflammatory Proteins Proteins 0.000 description 6
- 101150111110 NKX2-1 gene Proteins 0.000 description 6
- 230000003828 downregulation Effects 0.000 description 6
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 5
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 5
- 102100037850 Interferon gamma Human genes 0.000 description 5
- 102100039364 Metalloproteinase inhibitor 1 Human genes 0.000 description 5
- 238000011579 SCID mouse model Methods 0.000 description 5
- 108010031374 Tissue Inhibitor of Metalloproteinase-1 Proteins 0.000 description 5
- 208000027418 Wounds and injury Diseases 0.000 description 5
- 239000002299 complementary DNA Substances 0.000 description 5
- 238000012258 culturing Methods 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 238000000684 flow cytometry Methods 0.000 description 5
- 208000014674 injury Diseases 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 230000000770 proinflammatory effect Effects 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 230000001629 suppression Effects 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- 102000007469 Actins Human genes 0.000 description 4
- 108010085238 Actins Proteins 0.000 description 4
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 4
- -1 Nanog Proteins 0.000 description 4
- 210000002821 alveolar epithelial cell Anatomy 0.000 description 4
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 239000003246 corticosteroid Substances 0.000 description 4
- 229960001334 corticosteroids Drugs 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 230000007115 recruitment Effects 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 4
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 102000009193 Caveolin Human genes 0.000 description 3
- 108050000084 Caveolin Proteins 0.000 description 3
- 108010020382 Hepatocyte Nuclear Factor 1-alpha Proteins 0.000 description 3
- 102100022057 Hepatocyte nuclear factor 1-alpha Human genes 0.000 description 3
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 3
- 102100023974 Keratin, type II cytoskeletal 7 Human genes 0.000 description 3
- 108010070507 Keratin-7 Proteins 0.000 description 3
- 102100026261 Metalloproteinase inhibitor 3 Human genes 0.000 description 3
- 102000035195 Peptidases Human genes 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- 108010031429 Tissue Inhibitor of Metalloproteinase-3 Proteins 0.000 description 3
- 108091023040 Transcription factor Proteins 0.000 description 3
- 102000040945 Transcription factor Human genes 0.000 description 3
- 102000004142 Trypsin Human genes 0.000 description 3
- 108090000631 Trypsin Proteins 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 229940124630 bronchodilator Drugs 0.000 description 3
- 239000000168 bronchodilator agent Substances 0.000 description 3
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 3
- 210000001671 embryonic stem cell Anatomy 0.000 description 3
- 210000002744 extracellular matrix Anatomy 0.000 description 3
- 230000003176 fibrotic effect Effects 0.000 description 3
- 210000001654 germ layer Anatomy 0.000 description 3
- 229960002591 hydroxyproline Drugs 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 210000005265 lung cell Anatomy 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 238000010172 mouse model Methods 0.000 description 3
- 238000001543 one-way ANOVA Methods 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000000779 smoke Substances 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 3
- 239000012588 trypsin Substances 0.000 description 3
- 230000003827 upregulation Effects 0.000 description 3
- 210000003462 vein Anatomy 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 102000004392 Aquaporin 5 Human genes 0.000 description 2
- 108090000976 Aquaporin 5 Proteins 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 206010061818 Disease progression Diseases 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 108010048671 Homeodomain Proteins Proteins 0.000 description 2
- 102000009331 Homeodomain Proteins Human genes 0.000 description 2
- 101500025419 Homo sapiens Epidermal growth factor Proteins 0.000 description 2
- 102000008070 Interferon-gamma Human genes 0.000 description 2
- 102000003814 Interleukin-10 Human genes 0.000 description 2
- 108090000174 Interleukin-10 Proteins 0.000 description 2
- 102000004388 Interleukin-4 Human genes 0.000 description 2
- 108090000978 Interleukin-4 Proteins 0.000 description 2
- 102100026262 Metalloproteinase inhibitor 2 Human genes 0.000 description 2
- 102100024289 Metalloproteinase inhibitor 4 Human genes 0.000 description 2
- 108050006579 Metalloproteinase inhibitor 4 Proteins 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 102000002658 Thyroid Nuclear Factor 1 Human genes 0.000 description 2
- 108010057966 Thyroid Nuclear Factor 1 Proteins 0.000 description 2
- 108010031372 Tissue Inhibitor of Metalloproteinase-2 Proteins 0.000 description 2
- 102000009618 Transforming Growth Factors Human genes 0.000 description 2
- 108010009583 Transforming Growth Factors Proteins 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 230000003510 anti-fibrotic effect Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000007640 basal medium Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000001172 blastoderm Anatomy 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 210000001136 chorion Anatomy 0.000 description 2
- 210000004087 cornea Anatomy 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000009795 derivation Methods 0.000 description 2
- 230000005750 disease progression Effects 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 210000004700 fetal blood Anatomy 0.000 description 2
- 238000005206 flow analysis Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 229940116978 human epidermal growth factor Drugs 0.000 description 2
- 229960000890 hydrocortisone Drugs 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 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
- 229960003130 interferon gamma Drugs 0.000 description 2
- 229940076144 interleukin-10 Drugs 0.000 description 2
- 229940028885 interleukin-4 Drugs 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 230000007040 lung development Effects 0.000 description 2
- 230000004199 lung function Effects 0.000 description 2
- 239000003580 lung surfactant Substances 0.000 description 2
- 210000001161 mammalian embryo Anatomy 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 210000000651 myofibroblast Anatomy 0.000 description 2
- GVUGOAYIVIDWIO-UFWWTJHBSA-N nepidermin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C1=CC=C(O)C=C1 GVUGOAYIVIDWIO-UFWWTJHBSA-N 0.000 description 2
- 229960003512 nicotinic acid Drugs 0.000 description 2
- 235000001968 nicotinic acid Nutrition 0.000 description 2
- 239000011664 nicotinic acid Substances 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 210000001778 pluripotent stem cell Anatomy 0.000 description 2
- 230000002028 premature Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000008929 regeneration Effects 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- 229930002330 retinoic acid Natural products 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 229960003080 taurine Drugs 0.000 description 2
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 229960001727 tretinoin Drugs 0.000 description 2
- 210000002993 trophoblast Anatomy 0.000 description 2
- 238000007805 zymography Methods 0.000 description 2
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- HSTOKWSFWGCZMH-UHFFFAOYSA-N 3,3'-diaminobenzidine Chemical compound C1=C(N)C(N)=CC=C1C1=CC=C(N)C(N)=C1 HSTOKWSFWGCZMH-UHFFFAOYSA-N 0.000 description 1
- WUIABRMSWOKTOF-OYALTWQYSA-O 3-[[2-[2-[2-[[(2s,3r)-2-[[(2s,3s,4r)-4-[[(2s,3r)-2-[[6-amino-2-[(1s)-3-amino-1-[[(2s)-2,3-diamino-3-oxopropyl]amino]-3-oxopropyl]-5-methylpyrimidine-4-carbonyl]amino]-3-[(2r,3s,4s,5s,6s)-3-[(2r,3s,4s,5r,6r)-4-carbamoyloxy-3,5-dihydroxy-6-(hydroxymethyl)ox Chemical compound OS(O)(=O)=O.N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C WUIABRMSWOKTOF-OYALTWQYSA-O 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 101150029409 CFTR gene Proteins 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- 102000004266 Collagen Type IV Human genes 0.000 description 1
- 108010042086 Collagen Type IV Proteins 0.000 description 1
- 206010010099 Combined immunodeficiency Diseases 0.000 description 1
- 102000010831 Cytoskeletal Proteins Human genes 0.000 description 1
- 108010037414 Cytoskeletal Proteins Proteins 0.000 description 1
- 102100021238 Dynamin-2 Human genes 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
- 102000016942 Elastin Human genes 0.000 description 1
- 108010014258 Elastin Proteins 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 102400001368 Epidermal growth factor Human genes 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 102000013382 Gelatinases Human genes 0.000 description 1
- 108010026132 Gelatinases Proteins 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 102100028972 HLA class I histocompatibility antigen, A alpha chain Human genes 0.000 description 1
- 108010075704 HLA-A Antigens Proteins 0.000 description 1
- 102000015789 HLA-DP Antigens Human genes 0.000 description 1
- 108010010378 HLA-DP Antigens Proteins 0.000 description 1
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
- 101000817607 Homo sapiens Dynamin-2 Proteins 0.000 description 1
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
- 101000572820 Homo sapiens MICOS complex subunit MIC60 Proteins 0.000 description 1
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 1
- 101000800116 Homo sapiens Thy-1 membrane glycoprotein Proteins 0.000 description 1
- 101100539360 Homo sapiens UCN3 gene Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102100023915 Insulin Human genes 0.000 description 1
- 102100027998 Macrophage metalloelastase Human genes 0.000 description 1
- 108010076501 Matrix Metalloproteinase 12 Proteins 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101100310657 Mus musculus Sox1 gene Proteins 0.000 description 1
- 102000003945 NF-kappa B Human genes 0.000 description 1
- 108010057466 NF-kappa B Proteins 0.000 description 1
- 102000002584 Octamer Transcription Factor-3 Human genes 0.000 description 1
- 108010068425 Octamer Transcription Factor-3 Proteins 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 1
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 1
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 1
- 108010007125 Pulmonary Surfactant-Associated Protein C Proteins 0.000 description 1
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 1
- 102000003743 Relaxin Human genes 0.000 description 1
- 108090000103 Relaxin Proteins 0.000 description 1
- 208000004756 Respiratory Insufficiency Diseases 0.000 description 1
- 206010043276 Teratoma Diseases 0.000 description 1
- 241000906446 Theraps Species 0.000 description 1
- 102100033523 Thy-1 membrane glycoprotein Human genes 0.000 description 1
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical compound IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 description 1
- 102000004338 Transferrin Human genes 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 1
- COQLPRJCUIATTQ-UHFFFAOYSA-N Uranyl acetate Chemical compound O.O.O=[U]=O.CC(O)=O.CC(O)=O COQLPRJCUIATTQ-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
- 210000001552 airway epithelial cell Anatomy 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 210000002383 alveolar type I cell Anatomy 0.000 description 1
- 210000003425 amniotic epithelial cell Anatomy 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000019552 anatomical structure morphogenesis Effects 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 210000002159 anterior chamber Anatomy 0.000 description 1
- 230000002300 anti-fibrosis Effects 0.000 description 1
- 230000002529 anti-mitochondrial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 229940124748 beta 2 agonist Drugs 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 230000002051 biphasic effect Effects 0.000 description 1
- 210000002459 blastocyst Anatomy 0.000 description 1
- 229940040609 bleomycin injection Drugs 0.000 description 1
- 229960004395 bleomycin sulfate Drugs 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 239000007978 cacodylate buffer Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000001364 causal effect Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 239000002771 cell marker Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 230000008045 co-localization Effects 0.000 description 1
- 230000037319 collagen production Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 210000000795 conjunctiva Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 210000003785 decidua Anatomy 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 230000002222 downregulating effect Effects 0.000 description 1
- 229920002549 elastin Polymers 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 230000009786 epithelial differentiation Effects 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 210000003560 epithelium corneal Anatomy 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001400 expression cloning Methods 0.000 description 1
- 210000002219 extraembryonic membrane Anatomy 0.000 description 1
- 230000004720 fertilization Effects 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 238000007804 gelatin zymography Methods 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 208000035474 group of disease Diseases 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- 102000046079 human IMMT Human genes 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000002991 immunohistochemical analysis Methods 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 238000012332 laboratory investigation Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 231100000516 lung damage Toxicity 0.000 description 1
- 229940066294 lung surfactant Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000005399 mechanical ventilation Methods 0.000 description 1
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 1
- 210000000110 microvilli Anatomy 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 210000000472 morula Anatomy 0.000 description 1
- 210000002894 multi-fate stem cell Anatomy 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000004768 organ dysfunction Effects 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 1
- 239000012285 osmium tetroxide Substances 0.000 description 1
- 230000032696 parturition Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 102000013415 peroxidase activity proteins Human genes 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 201000004193 respiratory failure Diseases 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000023895 stem cell maintenance Effects 0.000 description 1
- 238000013517 stratification Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 238000004627 transmission electron microscopy Methods 0.000 description 1
- 229940035722 triiodothyronine Drugs 0.000 description 1
- 208000037999 tubulointerstitial fibrosis Diseases 0.000 description 1
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 1
- 238000010246 ultrastructural analysis Methods 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 210000003934 vacuole Anatomy 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/48—Reproductive organs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/01—Hydrocarbons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/48—Reproductive organs
- A61K35/50—Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0603—Embryonic cells ; Embryoid bodies
- C12N5/0605—Cells from extra-embryonic tissues, e.g. placenta, amnion, yolk sac, Wharton's jelly
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Developmental Biology & Embryology (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Cell Biology (AREA)
- Reproductive Health (AREA)
- Biotechnology (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Pregnancy & Childbirth (AREA)
- Virology (AREA)
- Gynecology & Obstetrics (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pulmonology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
本特許出願は、2007年5月28日に出願された「慢性肺疾患の治療」という名称の豪州特許第2007902844号により優先権を主張する。この出願の内容全体は参照することにより本明細書に組み込まれる。
羊膜及び絨毛膜は、外層を含む母性由来の脱落膜と共に胎盤の胚由来の内層の一部を形成する。絨毛膜が栄養膜に由来する一方で、羊膜は胚盤葉上層から生じ(すなわち、ヒトの受精8日後)、胚盤葉上層が胚の3種の胚葉の起源でもあるため、羊膜上皮細胞が多能性/複能性幹細胞の直接の供給源である可能性が示唆されてきた(すなわち、幹細胞は多様な細胞型に分化し得る)(Ilancheran, S., et al., 2007)。
報告されている。特に、人工呼吸器は細菌感染症に反応して肺の炎症を悪化させることが確認された(Dhanireddy, S., et al., 2006)。したがって、本発明の方法は、人工呼吸器の使用から生じる肺症状(すなわち、人工呼吸関連肺損傷(VALI))の治療にも使用することができる。
[実施例]
材料と方法
hAECの単離及び培養
分娩時、帝王切開を選択した女性から羊膜を得た。hAECは単離され、以前記載された方法(Ilancheran, S., et al., 2007)を使用して特徴付けした。すなわち、組織を0.25%のトリプシン:EDTA溶液(Invitrogen Corporation社製(米国CA州Carlsbad))中で2回、20分間消化させた。トリプシンを、ウシ胎仔血清(FCS、 Invitrogen社製)を使用して不活性化し、分散細胞はM199培地(Invitrogen社製)で洗浄した。次にhAECで見い出された上皮細胞骨格タンパク質であるサイトケラチン7(Dako Denmark A/S社製(デンマ−クGlostrup))についてフローサイトメトリーで細胞を分析した。サイトケラチン7陽性細胞を99%より多く有するバッチをIV型コラーゲン(Roche Diagnostics社製(スイスBasel))でコーティングした容器の上にプレーティングし、末梢気道上皮基底培地(SABM)(Clonetics社製(米国MD州Walersville))において培養し、補充物(すなわち、レチノイン酸、上皮細胞増殖因子1(EGF−1)、エピネフリン、トランスフェリン、インスリン、トリヨ−ドサイロニン、ウシ下垂体抽出液、ウシ血清アルブミン(BSA)、無脂肪酸血清及びヒドロコルチゾン)を加えた。対照培養物を10%ヒト血清又はFCSを有するDMEM/F−12培地(Invitrogen社製)で培養した。培養は4週間維持された(n=12)。
全RNAをRNeasy column(Qiagen社製(ドイツHilden))を使用してhAEC(n=6)から単離した。全RNAの1μgを、High−Capacity cDNA Archive Kit (Applied Biosystems社製(米国CA州Foster City))を使用してcDNAに変換した。このcDNAを20倍に希釈し、試薬(TaqMan Universal PCR Master Mix、Applied Biosystems社製)、PCRプライマ−、及びOct−4、Sox−2、Nanog、Nkx2.1、SPC、AQ−5及びβ−アクチン(Applied Biosystems社製、各々#Hs01895061_u1、#Hs00602736_s1、#Hs02387400_g1、#NM_003317.3、#Hs00161628_m1、#Hs00387048_ml)用のプローブと混合した。
細胞を、2.5%のグルタルアルデヒドを含む0.1Mのカコジル酸塩緩衝液中に2時間室温(RT)にて固定化し、4℃で一晩放置した。その後、細胞を1%の四酸化オスミウムに後固定化し、段階的にアセトン内で脱水し、浸漬し、60℃で24時間スパ−樹脂に包埋した。極薄の部分(80nm)をその後3%の酢酸ウラニル及びRenoylds 染色剤で染色した。
hAEC(2.5×105)を、カベオリン(1:100)、AQ−5 (1:50)、SPC(1:50)、ヒト白血球抗原(HLA)−DP、−DQ、−DR(10μg/ml)又はアロフィコシアニン(allophytocyanin)(APC)と共役したHLA−A、−B、−C(10μl)に対する抗体と共に室温で1時間インキュベートした。幾度かの洗浄の後、細胞を1:10に希釈されたAPCと共役したロバ抗ウサギ(カベオリン)、ロバ抗ヤギ(AQ−5、SP−C)又はヤギ抗マウス(HLA−DP、−DQ、−DR)二次抗体と共に30分間室温でインキュベートした。細胞を余剰分の二次抗体を取り除くため洗浄し、フロ−サイトメトリ−によって分析した。カベオリン、AQ−5及びSPCのための一次抗体はSanta Cruz Biotechnology, Inc.社(米国CA州Santa Cruz)から、HLA抗体及び二次抗血清はBecton, Dickinson and Company社(米国NJ州Franklin Lakes)から購入した。さらに、ヒト骨髄間葉幹細胞(hMSC)と比較した、下記の表2に記載されている細胞表面マーカー(Becton, Dickinson and Company社製)に対するのと同様の手法及びモノクローナル抗体を使用して、hAEC(5回継代培養された集団(P5)を含む)のフロ−サイトメトリ−分析を行った。各マーカーに対して「陽性の」細胞型の細胞の割合を記録した。
生理食塩水(0.15mg)に溶解した硫酸ブレオマイシンを弱いエ−テル麻酔下で鼻腔内に投与し、生後8週間の重症複合免疫不全(SCID)マウス(n=30)に肺線維症を誘発させた。対照マウスに0.2mlの生理食塩水を注入する一方で、ブレオマイシン注入24時間後、前記マウスにhAEC(0.2ml中1×106)を尾静脈経由で注入した。生理食塩水をマウスのもう1つのグループ(n=15)の鼻腔内に投与したが、これらマウスにはこれ以上の処置を行わなかった。hAECの代わりにヒト肺線維芽細胞(1×106)を使用する平行実験も実施した。さらに、hAECを健康なマウス(n=12)にも注入した。また、ブレオマイシン投与2週間後に、他のSCIDマウスにhAEC(0.2mlの生理食塩水中1×106)を尾から注入した。これら後者の動物の対照には、ブレオマイシン投与2週間後に、hAECの代わりに肺切除術により単離した肺線維芽細胞(0.2mlの生理食塩水中1×106)をSCIDマウスに(尾から)注入した。動物は処置の2週間後及び4週間後に殺処分された(4週間後に殺処分されたマウスは、ブレオマイシン投与の2週間後にhAEC又は肺線維芽細胞を注入されたマウスのみである)。肺組織は瞬間冷凍され、−80℃にて保管され、パラフィン包埋のために10%のホルマリンで固定した。
5μmの厚さでパラフィン包埋された組織切片は、脱蝋され、再水和された。クエン酸塩緩衝液の加熱により抗原回復が実行された。内因性ペルオキシダ−ゼ活性をクエンチングし、非特異的結合を阻止した後、ヒトミトコンドリア内膜(IMM;1:10、AbD Serotec社製(英国Oxfordshire州Kidlington))及びヒトSPC(1:50、Santa Cruz Biotechnology, Inc.社製)に対する抗体と共に、1時間37℃にて切片を培養した。イソタイプが一致したマウスIgG2a及びヤギIgGが陰性対照としての切片に適用された。西洋ワサビペルオキシダ−ゼで標識されたビオチン−ストレプトアビジン二次抗体(LSABキット、Dako社製)を使用して抗体結合を検出し、3,3′−ジアミノベンジジン色原体を使用して免疫染色を視覚化した。IMM及びSPCの共局在化を、連続組織切片を試験することにより評価した。炎症及び線維症については、アシュクロフト法(Ashcroft, T., et al., 1988)により切片を点数化した。
生理食塩水、ブレオマイシン及びブレオマイシン+hAEC(n=5/グループ)が注入されてから2週間後及び4週間後のSCIDマウスの肺から全RNAを抽出した。DNAse処理に続いて、1μgのRNAをSuperscriptIII(Invitrogen社製)を使用してcDNAに変換した。かかるcDNA(1:20に希釈)は、IL−1、IL−2、インターロイキン4(IL−4)、IL−6、インターロイキン−10(IL−10)、インターフェロン−γ(INF−γ)、TNF−α、TGF−β、MIF及びMIPに対してPCRプライマ−を使用して増幅した。定量PCRに使用されるサイクルパラメ−タは以下の通りであった:変性95℃、7秒間、アニ−リング60℃、7〜15秒間、及び伸長72℃、15秒間で40サイクル行った。β−アクチンにデ−タを標準化した後、生理食塩水で処理した対照マウスに対する発現を、ΔΔCt法によって計算した。
生理食塩水、ブレオマイシン及びブレオマイシン+hAEC(n=6/グループ)を注入したマウスの肺のコラーゲン含有量を、以前に記載されたように(Hewitson,T.D., et al., 2007)、ヒドロキシプロリンアッセイを使用して測定した。すなわち、肺を凍結乾燥し、HCIにて加水分解し、558nmでの吸光度を測定した。コラーゲン含有量はヒドロキシプロリンの測定結果に6.94を乗じることによって計算され、組織の乾燥重量の比率で示される(Gallop,P.M. and M.A.Paz, 1975)。
MMPをマウスの3つのグループ(n=6/グループ)から得た組織から抽出した。MMP−2及びMMP−9活性は、以前記載された(Woessner, J.F.Jr, 1995)ゼラチンザイモグラフィにより評価した。ザイモグラフは密度計(Gel Scan−710、Bio−Rad Laboratories, Inc.,社製(米国CA州Hercules)で走査され、Quantity−Oneソフトウエア(Bio−Rad社製)を使用してゼラチナ−ゼ活性を定量化した。かかるデ−タは平均値±標準誤差にて示された。
異なるグループ間の処理効果を、一元配置分散分析を使用して分析した。P<0.05は統計的に有意であると考えられた。
hAECを、細胞膜を剥離し、hAECを細胞培養にて培養することにより胎盤から得た。これらの細胞はクロ−ンを明示し、胚盤葉上層の派生(Chambers I., et al., 2003及びMitsui K., et al., 2003)に一致して、いくつかの多能性マーカー、すなわち、Oct−4、Nanog、Sox−1及びc−kit(図1a及び表1)を発現した。CD31、CD34及びCD45マーカー(表1参照)に対して「陰性」であるため、かかる細胞は血管内皮又は造血系統ではなかった。比較フロ−サイトメトリ−分析において、HAECによる細胞表面マーカーの発現はhMSCのそれとはかなり相違し(hMSCの特徴であるCD90マーカーにおいて最も顕著である)、その結果hAECは異なる表現型を有することが示された。
1. Ali, N.N., et al., Derivation of type II alveolar epithelial cells from murine embryonic stem cells. Tissue Engineering 8:541−550 (2002).
2. Ashcroft, T., et al., Simple method of estimating severity of pulmonary fibrosis on a numerical scale. J Clin Pathol 41:467−470 (1988).
3. Berger, M.J., et al., Differentiation of umbilical cord blood−derived multilineage progenitor cells into respiratory epithelial cells. Cytotherapy 8:480−487 (2006).
4. Chambers I., et al., Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell 113(5):551−552 (2003).
5. Dhanireddy S., et al., Mechanical ventilation induces inflammation, lung injury, and extrapulmonary organ dysfunction in experimental pneumonia. Laboratory Investigation 86:790−799 (2006).
6. Gallop, P.M. and M.A. Paz, Posttranslational protein modifications, with special attention to collagen and elastin. Physiological Reviews 55:418−487 (1975).
7. Gurujeyalakshmi, G., et al., Taurine and niacin block lung injury and fibrosis by down−regulating bleomycin−induced activation of transcription nuclear factor−kappaB in mice. J Pharmacol Exp Therap 293:82−90 (2000).
8. Hewitson, T.D., et al., Endogenous relaxin is a naturally occurring modulator of experimental renal tubulointerstitial fibrosis. Endocrinology 148:660−669 (2007).
9. Hori, J., et al., Immunological characteristics of amniotic epithelium. Cornea 25:S53−58 (2006).
10. Ilancheran S., et al., Stem cells derived from human fetal membranes display multi−lineage differentiation potential. Biol Reprod 77:577−588 (2007).
11. Kang, H.R., et al., Transforming growth factor (TGF)−beta 1 stimulates pulmonary fibrosis and inflammation via a Bax−dependent, bid activated pathway that involves matrix metalloproteinase−12. J Biol Chem 282:7723−7732 (2007).
12. Mitsui K., et al., The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell 113(5):631−642 (2003).
13. Morley, C.J., et al., The biochemistry and physiology of fetal pulmonary surfactant. In "Pre−term labour". Proc. V study group of Royal College of Obstetrics and Gynaecology. Eds. Anderson, A.B., Berad, R., Brundenell, J.M. and Dunn, P.M., pp 261−272.
14. Parolini, O., et al., Isolation and characterization of cells from human term placenta: outcome of the first international workshop on placenta derived stem cells. Stem Cells 26:300−311 (2008).
15. Selman, M. and A. Pardo, Potential role of proteases in pulmonary fibrosis. Annals of the New York Academy of Sciences 624:297−306 (1991).
16. Wang, M., et al., Immunogenicity and antigenicity of allogeneic amniotic epithelial transplants grafted to the cornea, conjunctiva, and anterior chamber. Investigative Ophthalmology & Visual Science 47:1522−1532 (2006).
17. Woessner, J.F. Jr, Quantification of matrix metaloproteinases in tissue samples. Methods in Enzymology 248:510−528 (1995).
Claims (27)
- 対象の肺疾患又は肺症状に対する細胞治療の方法であって、複能性羊膜上皮幹細胞(AEC)の治療有効量を前記対象に投与することを含む方法。
- AECがヒト羊膜上皮幹細胞(hAEC)であることを特徴とする、請求項1に記載の方法。
- hAECがOct−4、Nanog及びSox−2から選択される1又は複数のマーカーの発現により特徴付けられていることを特徴とする、請求項2に記載の方法。
- AECが分娩時又は分娩時間近の胎盤の羊膜由来であることを特徴とする、請求項1〜3のいずれかに記載の方法。
- AECが自己由来であることを特徴とする、請求項1〜4のいずれかに記載の方法。
- 治療される肺疾患又は肺症状が、慢性閉塞性肺疾患(COPD)、嚢胞性線維症(CF)、特発性肺線維症(IPF)、又は、化学療法及び/若しくは放射線療法、労働災害、又は毒性化合物若しくは毒性微粒子への暴露に起因する障害であることを特徴とする、請求項1〜5のいずれかに記載の方法。
- 治療される肺疾患又は肺症状が、急性呼吸促迫症候群(ARDS)又は急性肺損傷(ALI)であることを特徴とする、請求項1〜5のいずれかに記載の方法。
- 治療される肺疾患又は肺症状が、人工呼吸関連肺損傷(VALI)であることを特徴とする、請求項1〜5のいずれかに記載の方法。
- 治療される肺疾患又は肺症状が、胎児の呼吸窮迫症候群(RDS)であることを特徴とする、請求項1〜5のいずれかに記載の方法。
- AECが合成又は動物由来のサーファクタントと組み合わせて投与されることを特徴とする、請求項9に記載の方法。
- 対象の肺疾患又は肺症状に対する細胞療法のための組成物の調製における複能性羊膜上皮幹細胞(AEC)の使用であって、前記組成物が薬学的に許容される担体と組み合わせて前記AECを含む使用。
- AECがヒト羊膜上皮幹細胞(hAEC)であることを特徴とする、請求項11に記載の使用。
- hAECがOct−4、Nanog及びSox−2から選択される1又は複数のマーカーの発現により特徴付けられていることを特徴とする、請求項12に記載の使用。
- AECが分娩時又は分娩時間近の胎盤の羊膜由来であることを特徴とする、請求項11〜13のいずれかに記載の使用。
- AECが自己由来であることを特徴とする、請求項11〜14のいずれかに記載の使用。
- 治療される肺疾患又は肺症状が、慢性閉塞性肺疾患(COPD)、嚢胞性線維症(CF)、特発性肺線維症(IPF)、又は、化学療法及び/若しくは放射線療法、労働災害、又は毒性化合物若しくは毒性微粒子への暴露に起因する障害であることを特徴とする、請求項11〜15のいずれかに記載の使用。
- 治療される肺疾患又は肺症状が、急性呼吸促迫症候群(ARDS)又は急性肺損傷(ALI)であることを特徴とする、請求項11〜15のいずれかに記載の使用。
- 治療される肺疾患又は肺症状が、人工呼吸関連肺損傷(VALI)であることを特徴とする、請求項11〜15のいずれかに記載の使用。
- 肺疾患又は肺症状が、胎児の呼吸窮迫症候群(RDS)であることを特徴とする、請求項11〜15のいずれかに記載の使用。
- 組成物がさらに合成又は動物由来のサーファクタントを含むことを特徴とする、請求項19に記載の使用。
- 対象の肺の炎症を軽減させる方法であって、複能性羊膜上皮幹細胞(AEC)の治療有効量を前記対象に投与することを含む方法。
- 対象の肺線維症を予防する方法であって、複能性羊膜上皮幹細胞(AEC)の治療有効量を前記対象に投与することを含む方法。
- 対象の肺のコラーゲン濃度を低下させる方法であって、複能性羊膜上皮幹細胞(AEC)の治療有効量を前記対象に投与することを含む方法。
- AECがヒト羊膜上皮幹細胞(hAEC)であることを特徴とする、請求項21〜23のいずれかに記載の方法。
- hAECがOct−4、Nanog及びSox−2から選択される1又は複数のマーカーの発現により特徴付けられていることを特徴とする、請求項24に記載の方法。
- AECが分娩時又は分娩時間近の胎盤の羊膜由来であることを特徴とする、請求項21〜25のいずれかに記載の方法。
- AECが自己由来であることを特徴とする、請求項21〜26のいずれかに記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2007902844A AU2007902844A0 (en) | 2007-05-28 | Treatment of chronic lung disease | |
AU2007902844 | 2007-05-28 | ||
PCT/AU2008/000753 WO2008144820A1 (en) | 2007-05-28 | 2008-05-28 | Treatment of chronic lung disease |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2010528055A true JP2010528055A (ja) | 2010-08-19 |
JP5567476B2 JP5567476B2 (ja) | 2014-08-06 |
Family
ID=40074453
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2010509623A Expired - Fee Related JP5567476B2 (ja) | 2007-05-28 | 2008-05-28 | 慢性肺疾患の治療 |
Country Status (5)
Country | Link |
---|---|
US (1) | US20100266552A1 (ja) |
EP (1) | EP2164505B1 (ja) |
JP (1) | JP5567476B2 (ja) |
AU (1) | AU2008255634B2 (ja) |
WO (1) | WO2008144820A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2015504676A (ja) * | 2012-01-13 | 2015-02-16 | ザ ジェネラル ホスピタル コーポレイション | 単離ヒト肺前駆細胞およびその使用 |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10104880B2 (en) | 2008-08-20 | 2018-10-23 | Celularity, Inc. | Cell composition and methods of making the same |
EP2375907B1 (en) * | 2008-11-21 | 2019-02-27 | Celularity, Inc. | Treatment of diseases, disorders or conditions of the lung using placental cells |
CN101748096B (zh) * | 2008-12-17 | 2013-03-13 | 北京汉氏联合生物技术有限公司 | 亚全能干细胞、其制备方法及其用途 |
ES2620778T3 (es) * | 2009-02-04 | 2017-06-29 | Yale University | Ingeniería de tejidos de pulmón |
KR20180042217A (ko) * | 2015-06-12 | 2018-04-25 | 허드슨 인스티튜트 오브 메디컬 리서치 | 치료 방법 |
AU2017306580A1 (en) * | 2016-08-04 | 2019-02-21 | Hudson Institute of Medical Research | A method of treatment |
US10386368B2 (en) | 2017-02-24 | 2019-08-20 | Trustees Of Boston University | Isolation of human lung progenitors derived from pluripotent stem cells |
EP3593809A4 (en) * | 2017-03-08 | 2021-01-06 | Rohto Pharmaceutical Co., Ltd. | PHARMACEUTICAL COMPOSITION CONTAINING MMR1 POSITIVE MESENCHYMATIC STEM CELLS IN THE PROPHYLACTIC OR THERAPEUTIC TREATMENT OF A FIBROSIS-ASSOCIATED DISEASE, ITS PREPARATION PROCESS, AND PROCESS FOR THE PROPHYLACTIC TREATMENT OF FIBROSIS-ASSOCIATED DISEASE OR A FIBROSIS-ASSOCIATED THERAPEUTIC TREATMENT, AND PROCESS FOR THE PROPHYLACTIC TREATMENT OF FIBROSIS ASSOCIATED OR THERAPEUTIC TREATMENT MMR-POSITIVE MESENCHYMATIC STEM CELLS |
SG11202011927TA (en) * | 2018-06-05 | 2020-12-30 | Medipost Co Ltd | Pharmaceutical composition comprising mesenchymal stem cells as effective ingredient for prevention or treatment of inflammatory disease |
CN110101874A (zh) * | 2018-10-27 | 2019-08-09 | 广州呼吸健康研究院 | 一种利用hgf转基因的干细胞治疗ards的方法 |
CN110101873A (zh) * | 2018-10-27 | 2019-08-09 | 广州呼吸健康研究院 | 一种利用il-10转基因的干细胞治疗ards的方法 |
IT201800020722A1 (it) | 2018-12-21 | 2020-06-21 | Assunta Borzacchiello | Biomateriale e suo utilizzo nel trattamento di patologie polmonari |
CN111793596A (zh) * | 2019-12-06 | 2020-10-20 | 上海赛傲生物技术有限公司 | 一种人羊膜上皮干细胞的分离方法和制备方法 |
WO2021226602A1 (en) * | 2020-05-08 | 2021-11-11 | Celularity Inc. | Placenta-derived adherent (pda) stem cell for the treatment of adults with sars-cov-2 related acute respiratory failure and ards (covid-19) |
CN113679741B (zh) * | 2021-09-13 | 2023-09-19 | 北京大学第一医院 | 人羊膜上皮干细胞在制备治疗顺铂诱导的急性肾损伤的药物中的应用 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000073421A2 (en) * | 1999-06-02 | 2000-12-07 | Lifebank Services, L.L.C. | Methods of isolation, cryopreservation, and therapeutic use of human amniotic epithelial cells |
JP2002326943A (ja) * | 2001-02-28 | 2002-11-15 | Japan Tissue Engineering:Kk | 抗炎症剤 |
JP2004528021A (ja) * | 2001-02-14 | 2004-09-16 | アンスロジェネシス コーポレーション | 分娩後の哺乳動物の胎盤、その使用およびそれに由来する胎盤幹細胞 |
JP2005520516A (ja) * | 2002-03-15 | 2005-07-14 | モナシュ・ユニヴァーシティ | 幹細胞の特定細胞系統への分化を誘発する方法 |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU4520101A (en) * | 1999-12-07 | 2001-06-18 | Childrens Hospital Los Angeles Research Institute | Lung stem cells and lung regeneration |
US8021876B2 (en) * | 2001-11-15 | 2011-09-20 | Children's Medical Center Corporation | Methods of isolation, expansion and differentiation of fetal stem cells from chorionic villus, amniotic fluid, and placenta and therapeutic uses thereof |
US20030235563A1 (en) * | 2002-04-19 | 2003-12-25 | Strom Stephen C. | Placental derived stem cells and uses thereof |
US20040161419A1 (en) * | 2002-04-19 | 2004-08-19 | Strom Stephen C. | Placental stem cells and uses thereof |
US7569385B2 (en) * | 2003-08-14 | 2009-08-04 | The Regents Of The University Of California | Multipotent amniotic fetal stem cells |
BRPI0708576A2 (pt) * | 2006-03-07 | 2011-05-31 | Geeta Shroff | composição compreedendo células-tronco embriÈnicas humanas e seus derivados, métodos de uso e métodos de preparação |
WO2008003042A2 (en) * | 2006-06-28 | 2008-01-03 | The University Of Medicine And Dentistry Of New Jersey | Amnion-derived stem cells and uses thereof |
DE202006010151U1 (de) * | 2006-06-29 | 2006-10-05 | Arcos Die Haarprofis Handels-Gmbh | Haarersatz mit Sicherungseinrichtungen und Sicherheitseinrichtung für Haarersatz |
WO2008036374A2 (en) * | 2006-09-21 | 2008-03-27 | Medistem Laboratories, Inc. | Allogeneic stem cell transplants in non-conditioned recipients |
-
2008
- 2008-05-28 JP JP2010509623A patent/JP5567476B2/ja not_active Expired - Fee Related
- 2008-05-28 US US12/601,570 patent/US20100266552A1/en not_active Abandoned
- 2008-05-28 WO PCT/AU2008/000753 patent/WO2008144820A1/en active Application Filing
- 2008-05-28 AU AU2008255634A patent/AU2008255634B2/en not_active Ceased
- 2008-05-28 EP EP08748014.1A patent/EP2164505B1/en not_active Not-in-force
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000073421A2 (en) * | 1999-06-02 | 2000-12-07 | Lifebank Services, L.L.C. | Methods of isolation, cryopreservation, and therapeutic use of human amniotic epithelial cells |
JP2004528021A (ja) * | 2001-02-14 | 2004-09-16 | アンスロジェネシス コーポレーション | 分娩後の哺乳動物の胎盤、その使用およびそれに由来する胎盤幹細胞 |
JP2002326943A (ja) * | 2001-02-28 | 2002-11-15 | Japan Tissue Engineering:Kk | 抗炎症剤 |
JP2005520516A (ja) * | 2002-03-15 | 2005-07-14 | モナシュ・ユニヴァーシティ | 幹細胞の特定細胞系統への分化を誘発する方法 |
Non-Patent Citations (5)
Title |
---|
JPN6013009415; Am. J. Med. Genet., 1992, Vol.44, pp.527-533 * |
JPN6013009418; Transplantation, 2004, Vol.78, No.10, pp.1439-1448 * |
JPN6013009421; J. Reproduktionsmed. Endokrinol., 2006, Vol.3, No.2, pp.117-126 * |
JPN6013064600; Proc. Natl. Acad. Sci. USA, 2003, Vol.100, No.14, pp.8407-8411 * |
JPN6013064602; 厚生労働科学研究費補助金 難治性疾患克服研究事業 びまん性肺疾患に関する調査研究班 平成18年度研究 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2015504676A (ja) * | 2012-01-13 | 2015-02-16 | ザ ジェネラル ホスピタル コーポレイション | 単離ヒト肺前駆細胞およびその使用 |
Also Published As
Publication number | Publication date |
---|---|
US20100266552A1 (en) | 2010-10-21 |
EP2164505A4 (en) | 2010-12-22 |
JP5567476B2 (ja) | 2014-08-06 |
AU2008255634A1 (en) | 2008-12-04 |
EP2164505B1 (en) | 2014-09-17 |
EP2164505A1 (en) | 2010-03-24 |
WO2008144820A1 (en) | 2008-12-04 |
AU2008255634B2 (en) | 2014-06-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5567476B2 (ja) | 慢性肺疾患の治療 | |
US10035834B2 (en) | Mesenchymal stem cells, compositions, and methods for treatment of cardiac tissue damage | |
JP2018118984A (ja) | 肺疾患及び肺障害の炎症促進性メディエータのhUTC調節 | |
JP6000982B2 (ja) | 臍由来細胞を使用する筋萎縮性側索硬化症の治療 | |
CN113559126A (zh) | 利用胎盘干细胞治疗疼痛 | |
JP2015532656A (ja) | 子癇前症の予防及び治療方法 | |
JP2012512911A (ja) | 肺ならびに肺の疾患および障害の治療 | |
JP7168653B2 (ja) | 間葉系幹細胞を含む甲状腺眼症を治療するための組成物 | |
TW201632620A (zh) | 使用前驅細胞治療視網膜變性 | |
WO2021103817A1 (zh) | 蜕膜nk细胞及其细胞亚群来源外泌体在制备不孕不育相关疾病药物及辅助治疗剂中的用途 | |
JP2022522357A (ja) | 羊水由来の細胞外小胞及び創傷治癒のためのその使用 | |
US20190134100A1 (en) | Method of inhibiting angiogenesis | |
US20210230537A1 (en) | Angiogenesis using stimulated placental stem cells | |
Zhao et al. | Human umbilical cord mesenchymal stem cell-derived exosomes inhibit ovarian granulosa cells inflammatory response through inhibition of NF-κB signaling in polycystic ovary syndrome | |
US20160324898A1 (en) | Compositions and methods for the treatment of alzheimer's disease | |
JP2023017816A (ja) | 胎盤接着性細胞を使用するリンパ浮腫および関連する状態の処置 | |
TW201836623A (zh) | 使用前驅細胞治療視網膜變性 | |
TW201729819A (zh) | 使用前驅細胞治療視網膜變性 | |
TW201811344A (zh) | 使用前驅細胞治療視網膜血管性疾病 | |
US20220023349A1 (en) | Treatment of cachexia using fibroblast cells and products thereof | |
WO2021217098A1 (en) | Treatment of virus-induced acute respiratory distress syndrome |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20110527 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120510 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130228 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130527 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130603 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130625 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130702 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130731 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140107 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140404 |
|
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: 20140609 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20140619 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5567476 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
LAPS | Cancellation because of no payment of annual fees |