JP2022524764A - 免疫調節性間葉系幹細胞 - Google Patents
免疫調節性間葉系幹細胞 Download PDFInfo
- Publication number
- JP2022524764A JP2022524764A JP2021553068A JP2021553068A JP2022524764A JP 2022524764 A JP2022524764 A JP 2022524764A JP 2021553068 A JP2021553068 A JP 2021553068A JP 2021553068 A JP2021553068 A JP 2021553068A JP 2022524764 A JP2022524764 A JP 2022524764A
- Authority
- JP
- Japan
- Prior art keywords
- cells
- mscs
- cell
- msc
- isolated
- 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.)
- Pending
Links
- 210000002901 mesenchymal stem cell Anatomy 0.000 title claims abstract description 114
- 230000002519 immonomodulatory effect Effects 0.000 title claims abstract description 13
- 210000004027 cell Anatomy 0.000 claims abstract description 135
- 239000000203 mixture Substances 0.000 claims abstract description 62
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 claims abstract description 27
- 230000002757 inflammatory effect Effects 0.000 claims abstract description 26
- 229960002986 dinoprostone Drugs 0.000 claims abstract description 25
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 claims abstract description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 17
- 201000010099 disease Diseases 0.000 claims abstract description 15
- 102000004127 Cytokines Human genes 0.000 claims abstract description 14
- 108090000695 Cytokines Proteins 0.000 claims abstract description 14
- 102000043131 MHC class II family Human genes 0.000 claims abstract description 14
- 108091054438 MHC class II family Proteins 0.000 claims abstract description 14
- 238000011282 treatment Methods 0.000 claims abstract description 11
- 102100032912 CD44 antigen Human genes 0.000 claims abstract description 8
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 claims abstract description 8
- 101000935043 Homo sapiens Integrin beta-1 Proteins 0.000 claims abstract description 8
- 102100025304 Integrin beta-1 Human genes 0.000 claims abstract description 8
- 101000800116 Homo sapiens Thy-1 membrane glycoprotein Proteins 0.000 claims abstract description 7
- 102100033523 Thy-1 membrane glycoprotein Human genes 0.000 claims abstract description 7
- 210000004271 bone marrow stromal cell Anatomy 0.000 claims description 69
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 claims description 38
- 230000028327 secretion Effects 0.000 claims description 29
- 210000004369 blood Anatomy 0.000 claims description 23
- 239000008280 blood Substances 0.000 claims description 23
- 108090001005 Interleukin-6 Proteins 0.000 claims description 17
- 238000002347 injection Methods 0.000 claims description 16
- 239000007924 injection Substances 0.000 claims description 16
- 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 claims description 14
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 14
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 14
- 230000004054 inflammatory process Effects 0.000 claims description 12
- 102000004887 Transforming Growth Factor beta Human genes 0.000 claims description 11
- 108090001012 Transforming Growth Factor beta Proteins 0.000 claims description 11
- 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 claims description 11
- 102000003814 Interleukin-10 Human genes 0.000 claims description 10
- 108090000174 Interleukin-10 Proteins 0.000 claims description 10
- 210000000130 stem cell Anatomy 0.000 claims description 7
- 102100037850 Interferon gamma Human genes 0.000 claims description 6
- 108010074328 Interferon-gamma Proteins 0.000 claims description 6
- 102000000589 Interleukin-1 Human genes 0.000 claims description 6
- 108010002352 Interleukin-1 Proteins 0.000 claims description 6
- 239000000725 suspension Substances 0.000 claims description 6
- 239000011886 peripheral blood Substances 0.000 claims description 5
- 210000005259 peripheral blood Anatomy 0.000 claims description 5
- 206010037660 Pyrexia Diseases 0.000 claims description 3
- 206010003246 arthritis Diseases 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 238000001361 intraarterial administration Methods 0.000 claims description 3
- 238000010255 intramuscular injection Methods 0.000 claims description 3
- 239000007927 intramuscular injection Substances 0.000 claims description 3
- 238000010253 intravenous injection Methods 0.000 claims description 3
- 201000008482 osteoarthritis Diseases 0.000 claims description 3
- 230000010412 perfusion Effects 0.000 claims description 3
- 208000023275 Autoimmune disease Diseases 0.000 claims description 2
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 2
- 206010020751 Hypersensitivity Diseases 0.000 claims description 2
- 230000007815 allergy Effects 0.000 claims description 2
- 208000006673 asthma Diseases 0.000 claims description 2
- 201000008937 atopic dermatitis Diseases 0.000 claims description 2
- 230000002685 pulmonary effect Effects 0.000 claims description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 2
- 210000002435 tendon Anatomy 0.000 claims description 2
- 230000000699 topical effect Effects 0.000 claims 2
- 208000036487 Arthropathies Diseases 0.000 claims 1
- 208000012659 Joint disease Diseases 0.000 claims 1
- 230000003412 degenerative effect Effects 0.000 claims 1
- 230000004968 inflammatory condition Effects 0.000 abstract 1
- 238000000034 method Methods 0.000 description 17
- 102000004889 Interleukin-6 Human genes 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 238000002965 ELISA Methods 0.000 description 12
- 230000003110 anti-inflammatory effect Effects 0.000 description 8
- 238000000684 flow cytometry Methods 0.000 description 8
- 210000002865 immune cell Anatomy 0.000 description 8
- 241000283073 Equus caballus Species 0.000 description 7
- 108091054437 MHC class I family Proteins 0.000 description 7
- 210000001744 T-lymphocyte Anatomy 0.000 description 7
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 6
- 230000004071 biological effect Effects 0.000 description 6
- 238000002659 cell therapy Methods 0.000 description 6
- 230000028993 immune response Effects 0.000 description 6
- 230000001506 immunosuppresive effect Effects 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 210000001616 monocyte Anatomy 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 108010012236 Chemokines Proteins 0.000 description 5
- 102000019034 Chemokines Human genes 0.000 description 5
- 241000283086 Equidae Species 0.000 description 5
- 102000043129 MHC class I family Human genes 0.000 description 5
- 210000003719 b-lymphocyte Anatomy 0.000 description 5
- 230000002860 competitive effect Effects 0.000 description 5
- 230000004069 differentiation Effects 0.000 description 5
- 239000001963 growth medium Substances 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 230000003834 intracellular effect Effects 0.000 description 5
- 210000004698 lymphocyte Anatomy 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 230000000770 proinflammatory effect Effects 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 230000004936 stimulating effect Effects 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- 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 4
- 238000008157 ELISA kit Methods 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000003146 anticoagulant agent Substances 0.000 description 4
- 229940127219 anticoagulant drug Drugs 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000003833 cell viability Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- 230000000877 morphologic effect Effects 0.000 description 4
- 102000013415 peroxidase activity proteins Human genes 0.000 description 4
- 108040007629 peroxidase activity proteins Proteins 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 238000011002 quantification Methods 0.000 description 4
- 238000003860 storage 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
- 238000002054 transplantation Methods 0.000 description 4
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 3
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 3
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 3
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 3
- 235000011941 Tilia x europaea Nutrition 0.000 description 3
- 210000001789 adipocyte Anatomy 0.000 description 3
- 230000000735 allogeneic effect Effects 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
- 229940114079 arachidonic acid Drugs 0.000 description 3
- 235000021342 arachidonic acid Nutrition 0.000 description 3
- 239000000090 biomarker Substances 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 210000001612 chondrocyte Anatomy 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000007710 freezing Methods 0.000 description 3
- 230000008014 freezing Effects 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- 230000035876 healing Effects 0.000 description 3
- 229920002674 hyaluronan Polymers 0.000 description 3
- 229960003160 hyaluronic acid Drugs 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 238000003018 immunoassay Methods 0.000 description 3
- 230000009851 immunogenic response Effects 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 239000004571 lime Substances 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 208000003857 African horse sickness Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000010392 Bone Fractures Diseases 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 108010067306 Fibronectins Proteins 0.000 description 2
- 102000016359 Fibronectins Human genes 0.000 description 2
- 206010017076 Fracture Diseases 0.000 description 2
- 229920002683 Glycosaminoglycan Polymers 0.000 description 2
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 2
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 2
- -1 IL-8 Chemical compound 0.000 description 2
- 206010062016 Immunosuppression Diseases 0.000 description 2
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 2
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 206010028780 Nasal ulcer Diseases 0.000 description 2
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 2
- 108010065472 Vimentin Proteins 0.000 description 2
- 102000013127 Vimentin Human genes 0.000 description 2
- 241000710886 West Nile virus Species 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 210000002449 bone cell Anatomy 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 2
- 229960003957 dexamethasone Drugs 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 208000009724 equine infectious anemia Diseases 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 239000006481 glucose medium Substances 0.000 description 2
- 230000003394 haemopoietic effect Effects 0.000 description 2
- 238000003365 immunocytochemistry Methods 0.000 description 2
- 229940088592 immunologic factor Drugs 0.000 description 2
- 239000002955 immunomodulating agent Substances 0.000 description 2
- 229940121354 immunomodulator Drugs 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 210000005087 mononuclear cell Anatomy 0.000 description 2
- 210000000663 muscle cell Anatomy 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 210000002381 plasma Anatomy 0.000 description 2
- 210000004623 platelet-rich plasma Anatomy 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 150000003180 prostaglandins Chemical class 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000010257 thawing Methods 0.000 description 2
- 230000017423 tissue regeneration Effects 0.000 description 2
- 210000005048 vimentin Anatomy 0.000 description 2
- 239000011534 wash buffer Substances 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- 230000029663 wound healing Effects 0.000 description 2
- GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 102000027791 CD44 antigen Human genes 0.000 description 1
- 108091016585 CD44 antigen Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 241000701081 Equid alphaherpesvirus 1 Species 0.000 description 1
- 241000701089 Equid alphaherpesvirus 4 Species 0.000 description 1
- 102100036242 HLA class II histocompatibility antigen, DQ alpha 2 chain Human genes 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 108010027412 Histocompatibility Antigens Class II Proteins 0.000 description 1
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000930801 Homo sapiens HLA class II histocompatibility antigen, DQ alpha 2 chain Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 108010022222 Integrin beta1 Proteins 0.000 description 1
- 102000003812 Interleukin-15 Human genes 0.000 description 1
- 108090000172 Interleukin-15 Proteins 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- 108010013709 Leukocyte Common Antigens Proteins 0.000 description 1
- 102000017095 Leukocyte Common Antigens Human genes 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 206010028741 Nasal inflammation Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102000004264 Osteopontin Human genes 0.000 description 1
- 108010081689 Osteopontin Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 206010040844 Skin exfoliation Diseases 0.000 description 1
- 210000004241 Th2 cell Anatomy 0.000 description 1
- 108010031650 Thy-1 Antigens Proteins 0.000 description 1
- 102000002689 Toll-like receptor Human genes 0.000 description 1
- 108020000411 Toll-like receptor Proteins 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 210000005006 adaptive immune system Anatomy 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 210000004381 amniotic fluid Anatomy 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000007234 antiinflammatory process Effects 0.000 description 1
- 206010003230 arteritis Diseases 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 238000010366 cell biology technique Methods 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000004624 confocal microscopy Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 230000035618 desquamation Effects 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 210000004700 fetal blood Anatomy 0.000 description 1
- 239000012595 freezing medium Substances 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 230000005571 horizontal transmission Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 239000000367 immunologic factor Substances 0.000 description 1
- 230000008975 immunomodulatory function Effects 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 239000003547 immunosorbent Substances 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 210000005007 innate immune system Anatomy 0.000 description 1
- 230000016507 interphase Effects 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 210000004976 peripheral blood cell Anatomy 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 210000001778 pluripotent stem cell Anatomy 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- YIBNHAJFJUQSRA-YNNPMVKQSA-N prostaglandin H2 Chemical compound C1[C@@H]2OO[C@H]1[C@H](/C=C/[C@@H](O)CCCCC)[C@H]2C\C=C/CCCC(O)=O YIBNHAJFJUQSRA-YNNPMVKQSA-N 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000009331 sowing Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000000717 tumor promoter Substances 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
- C12N5/0662—Stem cells
- C12N5/0668—Mesenchymal stem cells from other natural sources
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/02—Compounds of the arachidonic acid pathway, e.g. prostaglandins, leukotrienes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/03—Compounds acting on the NO pathway, e.g. nitrososarginine
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/10—Growth factors
- C12N2501/15—Transforming growth factor beta (TGF-β)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/20—Cytokines; Chemokines
- C12N2501/23—Interleukins [IL]
- C12N2501/231—Interleukin-10 (IL-10)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/11—Coculture with; Conditioned medium produced by blood or immune system cells
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Developmental Biology & Embryology (AREA)
- Chemical & Material Sciences (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Engineering & Computer Science (AREA)
- Rheumatology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Virology (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP19162270.3 | 2019-03-12 | ||
| EP19162270 | 2019-03-12 | ||
| PCT/EP2020/056625 WO2020182935A1 (en) | 2019-03-12 | 2020-03-12 | Immunomodulating mesenchymal stem cells |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2022524764A true JP2022524764A (ja) | 2022-05-10 |
Family
ID=65801891
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2021553068A Pending JP2022524764A (ja) | 2019-03-12 | 2020-03-12 | 免疫調節性間葉系幹細胞 |
Country Status (10)
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117915924A (zh) | 2021-07-08 | 2024-04-19 | 勃林格殷格翰比利时兽医公司 | 间充质干细胞用于治疗慢性肾病 |
| EP4366744A1 (en) | 2021-07-08 | 2024-05-15 | Boehringer Ingelheim Veterinary Medicine Belgium | Mesenchymal stem cells for use in the treatment of chronic gingivostomatitis |
| AU2022307748A1 (en) | 2021-07-08 | 2024-01-25 | Boehringer Ingelheim Veterinary Medicine Belgium | Mesenchymal stem cells for use in the treatment of osteoarthritis in animals |
| TW202320818A (zh) | 2021-07-08 | 2023-06-01 | 比利時商比利時百靈佳殷格翰動物醫藥公司 | 用於治療異位性皮膚炎之間葉幹細胞 |
| WO2024033462A1 (en) | 2022-08-11 | 2024-02-15 | Boehringer Ingelheim Vetmedica Gmbh | Mesenchymal stem cells for use in the treatment of insect-bite hypersensitivity in equines |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK1066052T3 (da) | 1998-03-18 | 2006-06-12 | Osiris Therapeutics Inc | Mesenchymstamceller til forebyggelse og behandling af immunreaktioner ved transplantationer |
| US20080095749A1 (en) * | 2004-03-22 | 2008-04-24 | Sudeepta Aggarwal | Mesenchymal stem cells and uses therefor |
| EP3461884A1 (en) | 2004-03-22 | 2019-04-03 | Mesoblast International Sàrl | Mesenchymal stem cells and uses therefor |
| US20140017787A1 (en) | 2010-10-11 | 2014-01-16 | Aline M. Betancourt | Mesenchymal stem cells and related therapies |
| AU2017235446A1 (en) | 2016-03-16 | 2018-11-08 | Cell Medicine, Inc. | Mesenchymal stem cells with enhanced efficacy |
-
2020
- 2020-03-12 BR BR112021017738A patent/BR112021017738A8/pt unknown
- 2020-03-12 MX MX2021010739A patent/MX2021010739A/es unknown
- 2020-03-12 US US17/436,640 patent/US20220154147A1/en active Pending
- 2020-03-12 CN CN202080018981.6A patent/CN113677789A/zh active Pending
- 2020-03-12 CA CA3132414A patent/CA3132414A1/en active Pending
- 2020-03-12 JP JP2021553068A patent/JP2022524764A/ja active Pending
- 2020-03-12 KR KR1020217029168A patent/KR20210139259A/ko unknown
- 2020-03-12 WO PCT/EP2020/056625 patent/WO2020182935A1/en active Application Filing
- 2020-03-12 EP EP20708513.5A patent/EP3938494A1/en active Pending
- 2020-03-12 AU AU2020235912A patent/AU2020235912A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| AU2020235912A1 (en) | 2021-10-07 |
| KR20210139259A (ko) | 2021-11-22 |
| MX2021010739A (es) | 2021-12-15 |
| CA3132414A1 (en) | 2020-09-17 |
| EP3938494A1 (en) | 2022-01-19 |
| CN113677789A (zh) | 2021-11-19 |
| BR112021017738A8 (pt) | 2022-08-02 |
| WO2020182935A1 (en) | 2020-09-17 |
| US20220154147A1 (en) | 2022-05-19 |
| BR112021017738A2 (US06244707-20010612-C00007.png) | 2021-11-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2022524764A (ja) | 免疫調節性間葉系幹細胞 | |
| Mosaad | Hematopoietic stem cells: an overview | |
| Bobis-Wozowicz et al. | Genetically modified adipose tissue− derived mesenchymal stem cells overexpressing CXCR4 display increased motility, invasiveness, and homing to bone marrow of NOD/SCID mice | |
| TWI299752B (en) | Multipotent placental stem cell and methods thereof | |
| Fazzina et al. | Potency testing of mesenchymal stromal cell growth expanded in human platelet lysate from different human tissues | |
| US20170121685A1 (en) | Mesenchymal stem cell-derived exosomes and their uses | |
| Turnovcova et al. | Properties and growth of human bone marrow mesenchymal stromal cells cultivated in different media | |
| ES2914692T3 (es) | Células madre adhesivas derivadas de cordón umbilical mejoradas, método de preparación para las mismas, y uso de las mismas | |
| WO2011069121A1 (en) | Mesenchymal stem cells (mscs) isolated from mobilized peripheral blood | |
| Abdelhamid et al. | Retinoic acid-mediated anti-inflammatory responses in equine immune cells stimulated by LPS and allogeneic mesenchymal stem cells | |
| JP2021107385A (ja) | 月経血由来幹細胞培養上清液を含む医薬組成物 | |
| US20150329827A1 (en) | Muse cells isolation and expansion | |
| KR101380561B1 (ko) | 말과동물 양수 유래 다분화능 줄기세포 및 그 제조방법 | |
| TWI642781B (zh) | 具優異細胞保護及免疫調節之ｑｕａｄｒｉ－正之基質細胞 | |
| WO2023216799A1 (zh) | 一种人nkt细胞系及其应用 | |
| KR20130056782A (ko) | 말과동물 양막-유래 중간엽 줄기세포 | |
| TW202319536A (zh) | 用於治療慢性腎病之間葉幹細胞 | |
| WO2021192670A1 (ja) | 間葉系幹細胞及び間葉系幹細胞用培地 | |
| US20210269768A1 (en) | Neonatal stromal cells having low mhc-i expression and uses therof | |
| TWI669399B (zh) | 體外擴增自然殺手細胞及自然殺手ｔ細胞之方法及其醫藥組成物 | |
| KR102011634B1 (ko) | 향상된 산후 부착형 세포 및 그의 용도 | |
| TWI669400B (zh) | 用於體外擴增自然殺手細胞及自然殺手ｔ細胞之無血清細胞培養液 | |
| CN110628715B (zh) | 体外扩增自然杀手细胞及自然杀手t细胞的方法及其医药组成物 | |
| Siegmund | Functional assessment of myeloid-derived suppressor cells, mesenchymal stromal cells, and regulatory T cells for the control of T-cell funtion: implications for the graft-versus-host disease | |
| Hastreiter | Protein malnutrition effects of perivascular bone marrow microenvironment on the regulation of hematopoiesis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20230310 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20240228 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20240305 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20240604 |