JP2020527038A - ヒト口腔粘膜幹細胞セクレトーム - Google Patents
ヒト口腔粘膜幹細胞セクレトーム Download PDFInfo
- Publication number
- JP2020527038A JP2020527038A JP2020501135A JP2020501135A JP2020527038A JP 2020527038 A JP2020527038 A JP 2020527038A JP 2020501135 A JP2020501135 A JP 2020501135A JP 2020501135 A JP2020501135 A JP 2020501135A JP 2020527038 A JP2020527038 A JP 2020527038A
- Authority
- JP
- Japan
- Prior art keywords
- hsa
- mir
- cell
- derived
- homsc
- 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
- 210000000130 stem cell Anatomy 0.000 title claims abstract description 88
- 239000000203 mixture Substances 0.000 claims abstract description 99
- 238000000034 method Methods 0.000 claims abstract description 52
- 230000017423 tissue regeneration Effects 0.000 claims abstract description 20
- 238000011282 treatment Methods 0.000 claims abstract description 19
- 108090000623 proteins and genes Proteins 0.000 claims description 100
- 102000004169 proteins and genes Human genes 0.000 claims description 98
- 210000004027 cell Anatomy 0.000 claims description 47
- 239000002609 medium Substances 0.000 claims description 42
- 206010012601 diabetes mellitus Diseases 0.000 claims description 37
- 239000002679 microRNA Substances 0.000 claims description 34
- 230000029663 wound healing Effects 0.000 claims description 33
- 102100021669 Stromal cell-derived factor 1 Human genes 0.000 claims description 32
- 208000027418 Wounds and injury Diseases 0.000 claims description 32
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 32
- 206010052428 Wound Diseases 0.000 claims description 27
- 108700011259 MicroRNAs Proteins 0.000 claims description 23
- 210000001808 exosome Anatomy 0.000 claims description 22
- 239000000126 substance Substances 0.000 claims description 22
- 210000001519 tissue Anatomy 0.000 claims description 22
- 108010008951 Chemokine CXCL12 Proteins 0.000 claims description 19
- 239000003102 growth factor Substances 0.000 claims description 19
- 102100035194 Placenta growth factor Human genes 0.000 claims description 17
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 claims description 17
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 17
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 17
- 201000010099 disease Diseases 0.000 claims description 17
- 102100038836 Superoxide dismutase [Cu-Zn] Human genes 0.000 claims description 16
- 101710139715 Superoxide dismutase [Cu-Zn] Proteins 0.000 claims description 16
- 102100027017 Latent-transforming growth factor beta-binding protein 2 Human genes 0.000 claims description 15
- 208000035475 disorder Diseases 0.000 claims description 15
- 230000006378 damage Effects 0.000 claims description 14
- 230000001737 promoting effect Effects 0.000 claims description 13
- -1 GNUB2 Proteins 0.000 claims description 12
- 101000617130 Homo sapiens Stromal cell-derived factor 1 Proteins 0.000 claims description 12
- 102100023757 Latent-transforming growth factor beta-binding protein 4 Human genes 0.000 claims description 12
- 208000014674 injury Diseases 0.000 claims description 11
- 210000002540 macrophage Anatomy 0.000 claims description 11
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 11
- 101001054649 Homo sapiens Latent-transforming growth factor beta-binding protein 2 Proteins 0.000 claims description 10
- 101001054646 Homo sapiens Latent-transforming growth factor beta-binding protein 3 Proteins 0.000 claims description 10
- 102100027000 Latent-transforming growth factor beta-binding protein 1 Human genes 0.000 claims description 10
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 claims description 10
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 claims description 10
- 239000002537 cosmetic Substances 0.000 claims description 10
- 210000000056 organ Anatomy 0.000 claims description 10
- 108020004414 DNA Proteins 0.000 claims description 9
- 108010082093 Placenta Growth Factor Proteins 0.000 claims description 9
- 230000004069 differentiation Effects 0.000 claims description 9
- 238000011069 regeneration method Methods 0.000 claims description 9
- 230000008439 repair process Effects 0.000 claims description 9
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 8
- 102000012192 Cystatin C Human genes 0.000 claims description 8
- 108010061642 Cystatin C Proteins 0.000 claims description 8
- 108010001498 Galectin 1 Proteins 0.000 claims description 8
- 102100021736 Galectin-1 Human genes 0.000 claims description 8
- 102100033299 Glia-derived nexin Human genes 0.000 claims description 8
- 101001001487 Homo sapiens Phosphatidylinositol-glycan biosynthesis class F protein Proteins 0.000 claims description 8
- 101000595923 Homo sapiens Placenta growth factor Proteins 0.000 claims description 8
- 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 claims description 8
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 8
- 241000894007 species Species 0.000 claims description 8
- 102000034615 Glial cell line-derived neurotrophic factor Human genes 0.000 claims description 7
- 108091010837 Glial cell line-derived neurotrophic factor Proteins 0.000 claims description 7
- 101000978212 Homo sapiens Latent-transforming growth factor beta-binding protein 4 Proteins 0.000 claims description 7
- 210000003169 central nervous system Anatomy 0.000 claims description 7
- 230000008929 regeneration Effects 0.000 claims description 7
- 102100036845 C-C motif chemokine 22 Human genes 0.000 claims description 6
- 102100036150 C-X-C motif chemokine 5 Human genes 0.000 claims description 6
- 108010083701 Chemokine CCL22 Proteins 0.000 claims description 6
- 101000658138 Homo sapiens Thymosin beta-10 Proteins 0.000 claims description 6
- 108090001117 Insulin-Like Growth Factor II Proteins 0.000 claims description 6
- 102100035846 Pigment epithelium-derived factor Human genes 0.000 claims description 6
- 102100034998 Thymosin beta-10 Human genes 0.000 claims description 6
- 239000007640 basal medium Substances 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 210000003714 granulocyte Anatomy 0.000 claims description 6
- 208000019622 heart disease Diseases 0.000 claims description 6
- 210000000653 nervous system Anatomy 0.000 claims description 6
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 230000007838 tissue remodeling Effects 0.000 claims description 6
- 230000008733 trauma Effects 0.000 claims description 6
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 claims description 5
- 102100032366 C-C motif chemokine 7 Human genes 0.000 claims description 5
- 102100036170 C-X-C motif chemokine 9 Human genes 0.000 claims description 5
- 101000947186 Homo sapiens C-X-C motif chemokine 5 Proteins 0.000 claims description 5
- 101000997803 Homo sapiens Glia-derived nexin Proteins 0.000 claims description 5
- 101001054659 Homo sapiens Latent-transforming growth factor beta-binding protein 1 Proteins 0.000 claims description 5
- 108091070514 Homo sapiens let-7b stem-loop Proteins 0.000 claims description 5
- 108091069047 Homo sapiens let-7i stem-loop Proteins 0.000 claims description 5
- 108091068853 Homo sapiens miR-100 stem-loop Proteins 0.000 claims description 5
- 108091044909 Homo sapiens miR-1206 stem-loop Proteins 0.000 claims description 5
- 108091044903 Homo sapiens miR-1234 stem-loop Proteins 0.000 claims description 5
- 108091069006 Homo sapiens miR-125b-1 stem-loop Proteins 0.000 claims description 5
- 108091069087 Homo sapiens miR-125b-2 stem-loop Proteins 0.000 claims description 5
- 108091044862 Homo sapiens miR-1260a stem-loop Proteins 0.000 claims description 5
- 108091069086 Homo sapiens miR-127 stem-loop Proteins 0.000 claims description 5
- 108091044829 Homo sapiens miR-1286 stem-loop Proteins 0.000 claims description 5
- 108091044796 Homo sapiens miR-1290 stem-loop Proteins 0.000 claims description 5
- 108091068958 Homo sapiens miR-184 stem-loop Proteins 0.000 claims description 5
- 108091068998 Homo sapiens miR-191 stem-loop Proteins 0.000 claims description 5
- 108091067692 Homo sapiens miR-199a-1 stem-loop Proteins 0.000 claims description 5
- 108091067467 Homo sapiens miR-199a-2 stem-loop Proteins 0.000 claims description 5
- 108091067484 Homo sapiens miR-199b stem-loop Proteins 0.000 claims description 5
- 108091067466 Homo sapiens miR-212 stem-loop Proteins 0.000 claims description 5
- 108091070492 Homo sapiens miR-23a stem-loop Proteins 0.000 claims description 5
- 108091070397 Homo sapiens miR-28 stem-loop Proteins 0.000 claims description 5
- 108091070398 Homo sapiens miR-29a stem-loop Proteins 0.000 claims description 5
- 108091065436 Homo sapiens miR-30e stem-loop Proteins 0.000 claims description 5
- 108091072959 Homo sapiens miR-3144 stem-loop Proteins 0.000 claims description 5
- 108091066993 Homo sapiens miR-339 stem-loop Proteins 0.000 claims description 5
- 108091067563 Homo sapiens miR-376a-1 stem-loop Proteins 0.000 claims description 5
- 108091063912 Homo sapiens miR-376a-2 stem-loop Proteins 0.000 claims description 5
- 108091055446 Homo sapiens miR-378h stem-loop Proteins 0.000 claims description 5
- 108091067552 Homo sapiens miR-379 stem-loop Proteins 0.000 claims description 5
- 108091061676 Homo sapiens miR-411 stem-loop Proteins 0.000 claims description 5
- 108091055444 Homo sapiens miR-4454 stem-loop Proteins 0.000 claims description 5
- 108091064368 Homo sapiens miR-514a-1 stem-loop Proteins 0.000 claims description 5
- 108091064369 Homo sapiens miR-514a-2 stem-loop Proteins 0.000 claims description 5
- 108091063558 Homo sapiens miR-514a-3 stem-loop Proteins 0.000 claims description 5
- 108091064468 Homo sapiens miR-518c stem-loop Proteins 0.000 claims description 5
- 108091064417 Homo sapiens miR-518d stem-loop Proteins 0.000 claims description 5
- 108091064467 Homo sapiens miR-520c stem-loop Proteins 0.000 claims description 5
- 108091061666 Homo sapiens miR-542 stem-loop Proteins 0.000 claims description 5
- 108091086476 Homo sapiens miR-543 stem-loop Proteins 0.000 claims description 5
- 108091055511 Homo sapiens miR-548ah stem-loop Proteins 0.000 claims description 5
- 108091061780 Homo sapiens miR-612 stem-loop Proteins 0.000 claims description 5
- 108091061633 Homo sapiens miR-626 stem-loop Proteins 0.000 claims description 5
- 108091060481 Homo sapiens miR-758 stem-loop Proteins 0.000 claims description 5
- 108091083060 Homo sapiens miR-7975 stem-loop Proteins 0.000 claims description 5
- 108091086506 Homo sapiens miR-888 stem-loop Proteins 0.000 claims description 5
- 102000004877 Insulin Human genes 0.000 claims description 5
- 108090001061 Insulin Proteins 0.000 claims description 5
- 101710178954 Latent-transforming growth factor beta-binding protein 1 Proteins 0.000 claims description 5
- 101710178974 Latent-transforming growth factor beta-binding protein 2 Proteins 0.000 claims description 5
- 101710178977 Latent-transforming growth factor beta-binding protein 4 Proteins 0.000 claims description 5
- 108010025020 Nerve Growth Factor Proteins 0.000 claims description 5
- 102000007072 Nerve Growth Factors Human genes 0.000 claims description 5
- 102000003683 Neurotrophin-4 Human genes 0.000 claims description 5
- 108090000099 Neurotrophin-4 Proteins 0.000 claims description 5
- 230000032683 aging Effects 0.000 claims description 5
- 229940077737 brain-derived neurotrophic factor Drugs 0.000 claims description 5
- 230000000711 cancerogenic effect Effects 0.000 claims description 5
- 231100000357 carcinogen Toxicity 0.000 claims description 5
- 239000003183 carcinogenic agent Substances 0.000 claims description 5
- 230000035876 healing Effects 0.000 claims description 5
- 210000003757 neuroblast Anatomy 0.000 claims description 5
- 239000003900 neurotrophic factor Substances 0.000 claims description 5
- 229940097998 neurotrophin 4 Drugs 0.000 claims description 5
- 210000000578 peripheral nerve Anatomy 0.000 claims description 5
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 5
- 208000020431 spinal cord injury Diseases 0.000 claims description 5
- 208000019553 vascular disease Diseases 0.000 claims description 5
- 102100038353 Gremlin-2 Human genes 0.000 claims description 4
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 claims description 4
- 101001032861 Homo sapiens Gremlin-2 Proteins 0.000 claims description 4
- 108091065981 Homo sapiens miR-155 stem-loop Proteins 0.000 claims description 4
- 102000004372 Insulin-like growth factor binding protein 2 Human genes 0.000 claims description 4
- 108090000964 Insulin-like growth factor binding protein 2 Proteins 0.000 claims description 4
- 102100020873 Interleukin-2 Human genes 0.000 claims description 4
- 108010002350 Interleukin-2 Proteins 0.000 claims description 4
- 102000004889 Interleukin-6 Human genes 0.000 claims description 4
- 108090001005 Interleukin-6 Proteins 0.000 claims description 4
- 102100026236 Interleukin-8 Human genes 0.000 claims description 4
- 108090001007 Interleukin-8 Proteins 0.000 claims description 4
- 238000002266 amputation Methods 0.000 claims description 4
- 230000033115 angiogenesis Effects 0.000 claims description 4
- 210000000845 cartilage Anatomy 0.000 claims description 4
- 230000006862 enzymatic digestion Effects 0.000 claims description 4
- 230000013632 homeostatic process Effects 0.000 claims description 4
- 229940088597 hormone Drugs 0.000 claims description 4
- 239000005556 hormone Substances 0.000 claims description 4
- 229940125396 insulin Drugs 0.000 claims description 4
- 229940100601 interleukin-6 Drugs 0.000 claims description 4
- 229940096397 interleukin-8 Drugs 0.000 claims description 4
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 230000004770 neurodegeneration Effects 0.000 claims description 4
- 201000001119 neuropathy Diseases 0.000 claims description 4
- 230000007823 neuropathy Effects 0.000 claims description 4
- 239000000049 pigment Substances 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 4
- 230000005855 radiation Effects 0.000 claims description 4
- 210000002435 tendon Anatomy 0.000 claims description 4
- 208000023275 Autoimmune disease Diseases 0.000 claims description 3
- 102100036848 C-C motif chemokine 20 Human genes 0.000 claims description 3
- 101710155834 C-C motif chemokine 7 Proteins 0.000 claims description 3
- 101710085500 C-X-C motif chemokine 9 Proteins 0.000 claims description 3
- 102000006433 Chemokine CCL22 Human genes 0.000 claims description 3
- 108010035532 Collagen Proteins 0.000 claims description 3
- 102000008186 Collagen Human genes 0.000 claims description 3
- 208000034656 Contusions Diseases 0.000 claims description 3
- 208000017701 Endocrine disease Diseases 0.000 claims description 3
- 206010017076 Fracture Diseases 0.000 claims description 3
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 3
- 101710183811 Glia-derived nexin Proteins 0.000 claims description 3
- 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 claims description 3
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 claims description 3
- 102100034221 Growth-regulated alpha protein Human genes 0.000 claims description 3
- 101000713099 Homo sapiens C-C motif chemokine 20 Proteins 0.000 claims description 3
- 101000746367 Homo sapiens Granulocyte colony-stimulating factor Proteins 0.000 claims description 3
- 101001069921 Homo sapiens Growth-regulated alpha protein Proteins 0.000 claims description 3
- 101000775053 Homo sapiens Neuroblast differentiation-associated protein AHNAK Proteins 0.000 claims description 3
- 101001073422 Homo sapiens Pigment epithelium-derived factor Proteins 0.000 claims description 3
- 108091072574 Homo sapiens miR-514b stem-loop Proteins 0.000 claims description 3
- 108091044760 Homo sapiens miR-548m stem-loop Proteins 0.000 claims description 3
- 102100027020 Latent-transforming growth factor beta-binding protein 3 Human genes 0.000 claims description 3
- 101710178976 Latent-transforming growth factor beta-binding protein 3 Proteins 0.000 claims description 3
- 102000016267 Leptin Human genes 0.000 claims description 3
- 108010092277 Leptin Proteins 0.000 claims description 3
- 206010065433 Ligament rupture Diseases 0.000 claims description 3
- 206010029113 Neovascularisation Diseases 0.000 claims description 3
- 102100031837 Neuroblast differentiation-associated protein AHNAK Human genes 0.000 claims description 3
- 208000025157 Oral disease Diseases 0.000 claims description 3
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 claims description 3
- 206010043248 Tendon rupture Diseases 0.000 claims description 3
- 230000022159 cartilage development Effects 0.000 claims description 3
- 239000002975 chemoattractant Substances 0.000 claims description 3
- 238000002512 chemotherapy Methods 0.000 claims description 3
- 229920001436 collagen Polymers 0.000 claims description 3
- 230000009519 contusion Effects 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 208000030533 eye disease Diseases 0.000 claims description 3
- 230000002518 glial effect Effects 0.000 claims description 3
- 208000027866 inflammatory disease Diseases 0.000 claims description 3
- 230000002757 inflammatory effect Effects 0.000 claims description 3
- 238000007918 intramuscular administration Methods 0.000 claims description 3
- 238000001990 intravenous administration Methods 0.000 claims description 3
- 208000017169 kidney disease Diseases 0.000 claims description 3
- 208000030194 mouth disease Diseases 0.000 claims description 3
- 230000011164 ossification Effects 0.000 claims description 3
- 208000023504 respiratory system disease Diseases 0.000 claims description 3
- 231100000241 scar Toxicity 0.000 claims description 3
- 230000036573 scar formation Effects 0.000 claims description 3
- 208000013363 skeletal muscle disease Diseases 0.000 claims description 3
- 208000017520 skin disease Diseases 0.000 claims description 3
- 238000007920 subcutaneous administration Methods 0.000 claims description 3
- 108091007504 ADAM10 Proteins 0.000 claims description 2
- 102100029769 ADAMTS-like protein 1 Human genes 0.000 claims description 2
- 102100022454 Actin, gamma-enteric smooth muscle Human genes 0.000 claims description 2
- 101710119858 Alpha-1-acid glycoprotein Proteins 0.000 claims description 2
- 102100034612 Annexin A4 Human genes 0.000 claims description 2
- 101150094024 Apod gene Proteins 0.000 claims description 2
- 102100022954 Apolipoprotein D Human genes 0.000 claims description 2
- 102100036597 Basement membrane-specific heparan sulfate proteoglycan core protein Human genes 0.000 claims description 2
- 102100037917 CD109 antigen Human genes 0.000 claims description 2
- 102100022002 CD59 glycoprotein Human genes 0.000 claims description 2
- 102100029756 Cadherin-6 Human genes 0.000 claims description 2
- 102100025579 Calmodulin-2 Human genes 0.000 claims description 2
- 102000014914 Carrier Proteins Human genes 0.000 claims description 2
- 102100022640 Collagen alpha-1(XV) chain Human genes 0.000 claims description 2
- 102100036213 Collagen alpha-2(I) chain Human genes 0.000 claims description 2
- 102100039551 Collagen triple helix repeat-containing protein 1 Human genes 0.000 claims description 2
- 102100024330 Collectin-12 Human genes 0.000 claims description 2
- 102100035436 Complement factor D Human genes 0.000 claims description 2
- 102100040515 Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial Human genes 0.000 claims description 2
- 101800000026 Dentin sialoprotein Proteins 0.000 claims description 2
- 102100026992 Dermcidin Human genes 0.000 claims description 2
- 102100034579 Desmoglein-1 Human genes 0.000 claims description 2
- 102100038199 Desmoplakin Human genes 0.000 claims description 2
- 102000003668 Destrin Human genes 0.000 claims description 2
- 108090000082 Destrin Proteins 0.000 claims description 2
- 102100030074 Dickkopf-related protein 1 Human genes 0.000 claims description 2
- 102100029921 Dipeptidyl peptidase 1 Human genes 0.000 claims description 2
- 102100039673 Disintegrin and metalloproteinase domain-containing protein 10 Human genes 0.000 claims description 2
- 102100031814 EGF-containing fibulin-like extracellular matrix protein 1 Human genes 0.000 claims description 2
- 102100032449 EGF-like repeat and discoidin I-like domain-containing protein 3 Human genes 0.000 claims description 2
- 102100036123 Far upstream element-binding protein 2 Human genes 0.000 claims description 2
- 102100023593 Fibroblast growth factor receptor 1 Human genes 0.000 claims description 2
- 102100020715 Fms-related tyrosine kinase 3 ligand protein Human genes 0.000 claims description 2
- 101710162577 Fms-related tyrosine kinase 3 ligand protein Proteins 0.000 claims description 2
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 claims description 2
- 102100040352 Heat shock 70 kDa protein 1A Human genes 0.000 claims description 2
- 102100034051 Heat shock protein HSP 90-alpha Human genes 0.000 claims description 2
- 102100035617 Heterogeneous nuclear ribonucleoprotein A/B Human genes 0.000 claims description 2
- 102100034523 Histone H4 Human genes 0.000 claims description 2
- 101000727998 Homo sapiens ADAMTS-like protein 1 Proteins 0.000 claims description 2
- 101000678433 Homo sapiens Actin, gamma-enteric smooth muscle Proteins 0.000 claims description 2
- 101000924461 Homo sapiens Annexin A4 Proteins 0.000 claims description 2
- 101001000001 Homo sapiens Basement membrane-specific heparan sulfate proteoglycan core protein Proteins 0.000 claims description 2
- 101000797758 Homo sapiens C-C motif chemokine 7 Proteins 0.000 claims description 2
- 101000947172 Homo sapiens C-X-C motif chemokine 9 Proteins 0.000 claims description 2
- 101000738399 Homo sapiens CD109 antigen Proteins 0.000 claims description 2
- 101000897400 Homo sapiens CD59 glycoprotein Proteins 0.000 claims description 2
- 101000794604 Homo sapiens Cadherin-6 Proteins 0.000 claims description 2
- 101000984150 Homo sapiens Calmodulin-2 Proteins 0.000 claims description 2
- 101000899935 Homo sapiens Collagen alpha-1(XV) chain Proteins 0.000 claims description 2
- 101000875067 Homo sapiens Collagen alpha-2(I) chain Proteins 0.000 claims description 2
- 101000746121 Homo sapiens Collagen triple helix repeat-containing protein 1 Proteins 0.000 claims description 2
- 101000909528 Homo sapiens Collectin-12 Proteins 0.000 claims description 2
- 101000737554 Homo sapiens Complement factor D Proteins 0.000 claims description 2
- 101000966982 Homo sapiens Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial Proteins 0.000 claims description 2
- 101000911659 Homo sapiens Dermcidin Proteins 0.000 claims description 2
- 101000924316 Homo sapiens Desmoglein-1 Proteins 0.000 claims description 2
- 101000864646 Homo sapiens Dickkopf-related protein 1 Proteins 0.000 claims description 2
- 101000793922 Homo sapiens Dipeptidyl peptidase 1 Proteins 0.000 claims description 2
- 101001065272 Homo sapiens EGF-containing fibulin-like extracellular matrix protein 1 Proteins 0.000 claims description 2
- 101001016381 Homo sapiens EGF-like repeat and discoidin I-like domain-containing protein 3 Proteins 0.000 claims description 2
- 101000851054 Homo sapiens Elastin Proteins 0.000 claims description 2
- 101000930766 Homo sapiens Far upstream element-binding protein 2 Proteins 0.000 claims description 2
- 101000827746 Homo sapiens Fibroblast growth factor receptor 1 Proteins 0.000 claims description 2
- 101000917159 Homo sapiens Filaggrin Proteins 0.000 claims description 2
- 101001037759 Homo sapiens Heat shock 70 kDa protein 1A Proteins 0.000 claims description 2
- 101001016865 Homo sapiens Heat shock protein HSP 90-alpha Proteins 0.000 claims description 2
- 101000854036 Homo sapiens Heterogeneous nuclear ribonucleoprotein A/B Proteins 0.000 claims description 2
- 101001067880 Homo sapiens Histone H4 Proteins 0.000 claims description 2
- 101000840566 Homo sapiens Insulin-like growth factor-binding protein 5 Proteins 0.000 claims description 2
- 101001013150 Homo sapiens Interstitial collagenase Proteins 0.000 claims description 2
- 101000691574 Homo sapiens Junction plakoglobin Proteins 0.000 claims description 2
- 101000958390 Homo sapiens Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA Proteins 0.000 claims description 2
- 101001011906 Homo sapiens Matrix metalloproteinase-14 Proteins 0.000 claims description 2
- 101001014059 Homo sapiens Metallothionein-2 Proteins 0.000 claims description 2
- 101000947699 Homo sapiens Microfibril-associated glycoprotein 4 Proteins 0.000 claims description 2
- 101000929583 Homo sapiens N(G),N(G)-dimethylarginine dimethylaminohydrolase 2 Proteins 0.000 claims description 2
- 101000602237 Homo sapiens Neuroblastoma suppressor of tumorigenicity 1 Proteins 0.000 claims description 2
- 101000866805 Homo sapiens Non-histone chromosomal protein HMG-17 Proteins 0.000 claims description 2
- 101001125854 Homo sapiens Peptidase inhibitor 16 Proteins 0.000 claims description 2
- 101000617720 Homo sapiens Pregnancy-specific beta-1-glycoprotein 5 Proteins 0.000 claims description 2
- 101000690940 Homo sapiens Pro-adrenomedullin Proteins 0.000 claims description 2
- 101000983583 Homo sapiens Procathepsin L Proteins 0.000 claims description 2
- 101000577619 Homo sapiens Profilin-1 Proteins 0.000 claims description 2
- 101001135402 Homo sapiens Prostaglandin-H2 D-isomerase Proteins 0.000 claims description 2
- 101000735893 Homo sapiens Proteasome subunit beta type-6 Proteins 0.000 claims description 2
- 101000804792 Homo sapiens Protein Wnt-5a Proteins 0.000 claims description 2
- 101001132652 Homo sapiens Retinoic acid receptor responder protein 2 Proteins 0.000 claims description 2
- 101000687673 Homo sapiens Small integral membrane protein 6 Proteins 0.000 claims description 2
- 101000820460 Homo sapiens Stomatin Proteins 0.000 claims description 2
- 101000800055 Homo sapiens Testican-1 Proteins 0.000 claims description 2
- 101000838350 Homo sapiens Tubulin alpha-1C chain Proteins 0.000 claims description 2
- 102100029225 Insulin-like growth factor-binding protein 5 Human genes 0.000 claims description 2
- 102100026153 Junction plakoglobin Human genes 0.000 claims description 2
- 102100038245 Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA Human genes 0.000 claims description 2
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 claims description 2
- 102100030216 Matrix metalloproteinase-14 Human genes 0.000 claims description 2
- 102100031347 Metallothionein-2 Human genes 0.000 claims description 2
- 102100036103 Microfibril-associated glycoprotein 4 Human genes 0.000 claims description 2
- 102100036658 N(G),N(G)-dimethylarginine dimethylaminohydrolase 2 Human genes 0.000 claims description 2
- 102100037142 Neuroblastoma suppressor of tumorigenicity 1 Human genes 0.000 claims description 2
- 102100031346 Non-histone chromosomal protein HMG-17 Human genes 0.000 claims description 2
- 108091034117 Oligonucleotide Proteins 0.000 claims description 2
- 102100026747 Osteomodulin Human genes 0.000 claims description 2
- 102100029324 Peptidase inhibitor 16 Human genes 0.000 claims description 2
- 102100022025 Pregnancy-specific beta-1-glycoprotein 5 Human genes 0.000 claims description 2
- 102100026651 Pro-adrenomedullin Human genes 0.000 claims description 2
- 102100026534 Procathepsin L Human genes 0.000 claims description 2
- 102100028857 Profilin-1 Human genes 0.000 claims description 2
- 102100033279 Prostaglandin-H2 D-isomerase Human genes 0.000 claims description 2
- 102100036128 Proteasome subunit beta type-6 Human genes 0.000 claims description 2
- 102100033914 Retinoic acid receptor responder protein 2 Human genes 0.000 claims description 2
- 101700004678 SLIT3 Proteins 0.000 claims description 2
- 102100025490 Slit homolog 1 protein Human genes 0.000 claims description 2
- 102100021685 Stomatin Human genes 0.000 claims description 2
- 102100033390 Testican-1 Human genes 0.000 claims description 2
- 102100028985 Tubulin alpha-1C chain Human genes 0.000 claims description 2
- 102000043366 Wnt-5a Human genes 0.000 claims description 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 claims description 2
- 230000003213 activating effect Effects 0.000 claims description 2
- 108091008324 binding proteins Proteins 0.000 claims description 2
- 238000012258 culturing Methods 0.000 claims description 2
- 239000012634 fragment Substances 0.000 claims description 2
- 239000001963 growth medium Substances 0.000 claims description 2
- 238000001361 intraarterial administration Methods 0.000 claims description 2
- 238000007912 intraperitoneal administration Methods 0.000 claims description 2
- 210000003734 kidney Anatomy 0.000 claims description 2
- 229940039781 leptin Drugs 0.000 claims description 2
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 claims description 2
- 210000001259 mesencephalon Anatomy 0.000 claims description 2
- 210000000440 neutrophil Anatomy 0.000 claims description 2
- 230000002093 peripheral effect Effects 0.000 claims description 2
- 108091033319 polynucleotide Proteins 0.000 claims description 2
- 102000040430 polynucleotide Human genes 0.000 claims description 2
- 239000002157 polynucleotide Substances 0.000 claims description 2
- 230000001172 regenerating effect Effects 0.000 claims description 2
- 210000000278 spinal cord Anatomy 0.000 claims description 2
- 230000000699 topical effect Effects 0.000 claims description 2
- 102000048143 Insulin-Like Growth Factor II Human genes 0.000 claims 4
- 230000000302 ischemic effect Effects 0.000 claims 3
- 102100037597 Brain-derived neurotrophic factor Human genes 0.000 claims 2
- 102100034871 C-C motif chemokine 8 Human genes 0.000 claims 2
- 229910017518 Cu Zn Inorganic materials 0.000 claims 2
- 229910017752 Cu-Zn Inorganic materials 0.000 claims 2
- 229910017943 Cu—Zn Inorganic materials 0.000 claims 2
- 208000018035 Dental disease Diseases 0.000 claims 2
- 102100021866 Hepatocyte growth factor Human genes 0.000 claims 2
- 206010061213 Iatrogenic injury Diseases 0.000 claims 2
- 208000012931 Urologic disease Diseases 0.000 claims 2
- 208000015114 central nervous system disease Diseases 0.000 claims 2
- TVZPLCNGKSPOJA-UHFFFAOYSA-N copper zinc Chemical compound [Cu].[Zn] TVZPLCNGKSPOJA-UHFFFAOYSA-N 0.000 claims 2
- 210000001428 peripheral nervous system Anatomy 0.000 claims 2
- 208000014001 urinary system disease Diseases 0.000 claims 2
- BNIFSVVAHBLNTN-XKKUQSFHSA-N (2s)-4-amino-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-1-[(2s)-4-amino-2-[[2-[[(2s)-2-[[(2s)-2-[[(2s)-1-[(2s)-6-amino-2-[[(2s)-2-[[(2s)-2-[[(2s,3r)-2-amino-3-hydroxybutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexan Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N1[C@H](C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(O)=O)CCC1 BNIFSVVAHBLNTN-XKKUQSFHSA-N 0.000 claims 1
- 101710155833 C-C motif chemokine 8 Proteins 0.000 claims 1
- 208000018380 Chemical injury Diseases 0.000 claims 1
- 101000946794 Homo sapiens C-C motif chemokine 8 Proteins 0.000 claims 1
- 208000012902 Nervous system disease Diseases 0.000 claims 1
- 208000025966 Neurological disease Diseases 0.000 claims 1
- 102100024806 Small integral membrane protein 6 Human genes 0.000 claims 1
- 208000026723 Urinary tract disease Diseases 0.000 claims 1
- 210000004556 brain Anatomy 0.000 claims 1
- 230000003399 chemotactic effect Effects 0.000 claims 1
- 208000010643 digestive system disease Diseases 0.000 claims 1
- 108700014844 flt3 ligand Proteins 0.000 claims 1
- 208000018685 gastrointestinal system disease Diseases 0.000 claims 1
- 210000002216 heart Anatomy 0.000 claims 1
- 238000007913 intrathecal administration Methods 0.000 claims 1
- AEUKDPKXTPNBNY-XEYRWQBLSA-N mcp 2 Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)C1=CC=CC=C1 AEUKDPKXTPNBNY-XEYRWQBLSA-N 0.000 claims 1
- 108091083308 miR-155 stem-loop Proteins 0.000 claims 1
- 108091091301 miR-155-1 stem-loop Proteins 0.000 claims 1
- 108091041686 miR-155-2 stem-loop Proteins 0.000 claims 1
- 210000005036 nerve Anatomy 0.000 claims 1
- 108010012038 peptide 78 Proteins 0.000 claims 1
- 229940125863 peptide 78 Drugs 0.000 claims 1
- 238000010586 diagram Methods 0.000 abstract description 8
- 230000003796 beauty Effects 0.000 abstract 1
- 235000018102 proteins Nutrition 0.000 description 77
- 241000699670 Mus sp. Species 0.000 description 29
- 210000003491 skin Anatomy 0.000 description 26
- 230000001225 therapeutic effect Effects 0.000 description 18
- 210000002200 mouth mucosa Anatomy 0.000 description 17
- 238000012549 training Methods 0.000 description 16
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 15
- 210000001185 bone marrow Anatomy 0.000 description 14
- 108091070501 miRNA Proteins 0.000 description 13
- 210000004400 mucous membrane Anatomy 0.000 description 12
- 230000014509 gene expression Effects 0.000 description 11
- 210000000933 neural crest Anatomy 0.000 description 11
- 206010028980 Neoplasm Diseases 0.000 description 9
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 9
- 239000002953 phosphate buffered saline Substances 0.000 description 9
- 239000003814 drug Substances 0.000 description 8
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 7
- 201000011510 cancer Diseases 0.000 description 7
- 210000002808 connective tissue Anatomy 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 102000004127 Cytokines Human genes 0.000 description 6
- 108090000695 Cytokines Proteins 0.000 description 6
- 210000004504 adult stem cell Anatomy 0.000 description 6
- 210000003981 ectoderm Anatomy 0.000 description 6
- 108020004707 nucleic acids Proteins 0.000 description 6
- 102000039446 nucleic acids Human genes 0.000 description 6
- 150000007523 nucleic acids Chemical class 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- 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 5
- 210000000577 adipose tissue Anatomy 0.000 description 5
- 239000002771 cell marker Substances 0.000 description 5
- 239000012091 fetal bovine serum Substances 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 210000000214 mouth Anatomy 0.000 description 5
- 238000003498 protein array Methods 0.000 description 5
- 102000053602 DNA Human genes 0.000 description 4
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 4
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 4
- 229930182555 Penicillin Natural products 0.000 description 4
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 4
- 210000005258 dental pulp stem cell Anatomy 0.000 description 4
- 210000003953 foreskin Anatomy 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- 210000001161 mammalian embryo Anatomy 0.000 description 4
- 210000004877 mucosa Anatomy 0.000 description 4
- 229940049954 penicillin Drugs 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 229960005322 streptomycin Drugs 0.000 description 4
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 3
- 102000019034 Chemokines Human genes 0.000 description 3
- 108010012236 Chemokines Proteins 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 241000237858 Gastropoda Species 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 102000003886 Glycoproteins Human genes 0.000 description 3
- 108090000288 Glycoproteins Proteins 0.000 description 3
- 102100025947 Insulin-like growth factor II Human genes 0.000 description 3
- 108020004566 Transfer RNA Proteins 0.000 description 3
- 208000025865 Ulcer Diseases 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 238000001574 biopsy Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 210000000988 bone and bone Anatomy 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 210000001163 endosome Anatomy 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 230000000642 iatrogenic effect Effects 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 230000001537 neural effect Effects 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 108090000102 pigment epithelium-derived factor Proteins 0.000 description 3
- 230000003248 secreting effect Effects 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 231100000397 ulcer Toxicity 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 229930182566 Gentamicin Natural products 0.000 description 2
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 2
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 description 2
- 101001139134 Homo sapiens Krueppel-like factor 4 Proteins 0.000 description 2
- 101000687905 Homo sapiens Transcription factor SOX-2 Proteins 0.000 description 2
- 206010021639 Incontinence Diseases 0.000 description 2
- 102100020677 Krueppel-like factor 4 Human genes 0.000 description 2
- 108020005196 Mitochondrial DNA Proteins 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 102000007999 Nuclear Proteins Human genes 0.000 description 2
- 108010089610 Nuclear Proteins Proteins 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- 208000010886 Peripheral nerve injury Diseases 0.000 description 2
- 108010067787 Proteoglycans Proteins 0.000 description 2
- 102000016611 Proteoglycans Human genes 0.000 description 2
- 108020004682 Single-Stranded DNA Proteins 0.000 description 2
- 206010072170 Skin wound Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 102100024270 Transcription factor SOX-2 Human genes 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 2
- 229960003942 amphotericin b Drugs 0.000 description 2
- 239000000090 biomarker Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 238000002659 cell therapy Methods 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000003636 conditioned culture medium Substances 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 210000003074 dental pulp Anatomy 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 208000037765 diseases and disorders Diseases 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 210000001671 embryonic stem cell Anatomy 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 210000002744 extracellular matrix Anatomy 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 229960002518 gentamicin Drugs 0.000 description 2
- 210000004195 gingiva Anatomy 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 210000002894 multi-fate stem cell Anatomy 0.000 description 2
- 201000006938 muscular dystrophy Diseases 0.000 description 2
- 208000031225 myocardial ischemia Diseases 0.000 description 2
- 210000005155 neural progenitor cell Anatomy 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 201000008482 osteoarthritis Diseases 0.000 description 2
- 210000003254 palate Anatomy 0.000 description 2
- 210000001778 pluripotent stem cell Anatomy 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 239000012679 serum free medium Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000002798 spectrophotometry method Methods 0.000 description 2
- 230000035882 stress Effects 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 238000011285 therapeutic regimen Methods 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- ROMPPAWVATWIKR-UHFFFAOYSA-N 4-[3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl]butanoic acid Chemical compound O1C(CCCC(=O)O)=NC(C=2C=CC(Cl)=CC=2)=N1 ROMPPAWVATWIKR-UHFFFAOYSA-N 0.000 description 1
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 1
- 102100027211 Albumin Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 102100022987 Angiogenin Human genes 0.000 description 1
- 206010059245 Angiopathy Diseases 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 229940122361 Bisphosphonate Drugs 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 102100036850 C-C motif chemokine 23 Human genes 0.000 description 1
- 102100039398 C-X-C motif chemokine 2 Human genes 0.000 description 1
- 101710085495 C-X-C motif chemokine 5 Proteins 0.000 description 1
- 102100025222 CD63 antigen Human genes 0.000 description 1
- 101100322915 Caenorhabditis elegans akt-1 gene Proteins 0.000 description 1
- 206010007558 Cardiac failure chronic Diseases 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 102100035345 Cerebral dopamine neurotrophic factor Human genes 0.000 description 1
- 229920001287 Chondroitin sulfate Polymers 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 1
- 208000032170 Congenital Abnormalities Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 206010011985 Decubitus ulcer Diseases 0.000 description 1
- 208000016192 Demyelinating disease Diseases 0.000 description 1
- 229920000045 Dermatan sulfate Polymers 0.000 description 1
- 208000002249 Diabetes Complications Diseases 0.000 description 1
- 206010012655 Diabetic complications Diseases 0.000 description 1
- 208000008960 Diabetic foot Diseases 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 206010056340 Diabetic ulcer Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 108010014258 Elastin Proteins 0.000 description 1
- 102000016942 Elastin Human genes 0.000 description 1
- 102100033167 Elastin Human genes 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 1
- 206010014989 Epidermolysis bullosa Diseases 0.000 description 1
- 208000007217 Esophageal Stenosis Diseases 0.000 description 1
- 108700039887 Essential Genes Proteins 0.000 description 1
- 102100037362 Fibronectin Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 206010016717 Fistula Diseases 0.000 description 1
- 208000003790 Foot Ulcer Diseases 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 208000035895 Guillain-Barré syndrome Diseases 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 1
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 1
- 229920002971 Heparan sulfate Polymers 0.000 description 1
- 101000713081 Homo sapiens C-C motif chemokine 23 Proteins 0.000 description 1
- 101000889128 Homo sapiens C-X-C motif chemokine 2 Proteins 0.000 description 1
- 101000934368 Homo sapiens CD63 antigen Proteins 0.000 description 1
- 101000737775 Homo sapiens Cerebral dopamine neurotrophic factor Proteins 0.000 description 1
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 1
- 101001076292 Homo sapiens Insulin-like growth factor II Proteins 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 1
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 1
- 108010028750 Integrin-Binding Sialoprotein Proteins 0.000 description 1
- 102000016921 Integrin-Binding Sialoprotein Human genes 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 239000000232 Lipid Bilayer Substances 0.000 description 1
- 108020005198 Long Noncoding RNA Proteins 0.000 description 1
- 206010049567 Miller Fisher syndrome Diseases 0.000 description 1
- 108010050619 Monokines Proteins 0.000 description 1
- 102000013967 Monokines Human genes 0.000 description 1
- 208000001089 Multiple system atrophy Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 208000007201 Myocardial reperfusion injury Diseases 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 206010030194 Oesophageal stenosis Diseases 0.000 description 1
- 208000003435 Optic Neuritis Diseases 0.000 description 1
- 206010031252 Osteomyelitis Diseases 0.000 description 1
- 102000004264 Osteopontin Human genes 0.000 description 1
- 108010081689 Osteopontin Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000027089 Parkinsonian disease Diseases 0.000 description 1
- 206010034010 Parkinsonism Diseases 0.000 description 1
- 241000721454 Pemphigus Species 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 208000004210 Pressure Ulcer Diseases 0.000 description 1
- 101710098940 Pro-epidermal growth factor Proteins 0.000 description 1
- 206010037779 Radiculopathy Diseases 0.000 description 1
- 101100247004 Rattus norvegicus Qsox1 gene Proteins 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical group [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 206010040943 Skin Ulcer Diseases 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- 101710088580 Stromal cell-derived factor 1 Proteins 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 108700031126 Tetraspanins Proteins 0.000 description 1
- 102000043977 Tetraspanins Human genes 0.000 description 1
- 206010043540 Thromboangiitis obliterans Diseases 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 208000000558 Varicose Ulcer Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 108010031318 Vitronectin Proteins 0.000 description 1
- 102100035140 Vitronectin Human genes 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 206010064930 age-related macular degeneration Diseases 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 210000001909 alveolar process Anatomy 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 108010072788 angiogenin Proteins 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 206010063452 arteriosclerotic retinopathy Diseases 0.000 description 1
- 206010003230 arteritis Diseases 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 210000000467 autonomic pathway Anatomy 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 150000004663 bisphosphonates Chemical class 0.000 description 1
- 210000002459 blastocyst Anatomy 0.000 description 1
- 230000010478 bone regeneration Effects 0.000 description 1
- 230000009702 cancer cell proliferation Effects 0.000 description 1
- 210000004413 cardiac myocyte Anatomy 0.000 description 1
- 230000034303 cell budding Effects 0.000 description 1
- 230000008568 cell cell communication Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 210000001612 chondrocyte Anatomy 0.000 description 1
- 229940059329 chondroitin sulfate Drugs 0.000 description 1
- 210000003040 circulating cell Anatomy 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000003210 demyelinating effect Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- AVJBPWGFOQAPRH-FWMKGIEWSA-L dermatan sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@H](OS([O-])(=O)=O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](C([O-])=O)O1 AVJBPWGFOQAPRH-FWMKGIEWSA-L 0.000 description 1
- 229940051593 dermatan sulfate Drugs 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 229920002549 elastin Polymers 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 210000002308 embryonic cell Anatomy 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000028023 exocytosis Effects 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 230000008175 fetal development Effects 0.000 description 1
- 230000019305 fibroblast migration Effects 0.000 description 1
- 230000003890 fistula Effects 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 229940044627 gamma-interferon Drugs 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000012252 genetic analysis Methods 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 229960002743 glutamine Drugs 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 239000001310 hydroxy propyl distarch phosphate Substances 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 238000003125 immunofluorescent labeling Methods 0.000 description 1
- 231100000405 induce cancer Toxicity 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229940068935 insulin-like growth factor 2 Drugs 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 208000036971 interstitial lung disease 2 Diseases 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000002601 intratumoral effect Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 208000037805 labour Diseases 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 102000005861 leptin receptors Human genes 0.000 description 1
- 108010019813 leptin receptors Proteins 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 210000004937 luminal membrane Anatomy 0.000 description 1
- 208000002780 macular degeneration Diseases 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000001617 migratory effect Effects 0.000 description 1
- 230000001483 mobilizing effect Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 230000023105 myelination Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- 210000003061 neural cell Anatomy 0.000 description 1
- 210000001982 neural crest cell Anatomy 0.000 description 1
- 210000001020 neural plate Anatomy 0.000 description 1
- 230000004766 neurogenesis Effects 0.000 description 1
- 230000004112 neuroprotection Effects 0.000 description 1
- 230000000508 neurotrophic effect Effects 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 235000003170 nutritional factors Nutrition 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- 230000002188 osteogenic effect Effects 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 230000003076 paracrine Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 208000006473 polyradiculopathy Diseases 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000004224 protection Effects 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000003938 response to stress Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 210000004116 schwann cell Anatomy 0.000 description 1
- 210000003497 sciatic nerve Anatomy 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 101150077014 sox10 gene Proteins 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000025366 tissue development Effects 0.000 description 1
- 230000009772 tissue formation Effects 0.000 description 1
- 230000030968 tissue homeostasis Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 230000010388 wound contraction Effects 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/185—Nerve growth factor [NGF]; Brain derived neurotrophic factor [BDNF]; Ciliary neurotrophic factor [CNTF]; Glial derived neurotrophic factor [GDNF]; Neurotrophins, e.g. NT-3
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/30—Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
- C07K14/4753—Hepatocyte growth factor; Scatter factor; Tumor cytotoxic factor II
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y115/00—Oxidoreductases acting on superoxide as acceptor (1.15)
- C12Y115/01—Oxidoreductases acting on superoxide as acceptor (1.15) with NAD or NADP as acceptor (1.15.1)
- C12Y115/01001—Superoxide dismutase (1.15.1.1)
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/713—Double-stranded nucleic acids or oligonucleotides
-
- 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
- A61K35/37—Digestive system
- A61K35/38—Stomach; Intestine; Goblet cells; Oral mucosa; Saliva
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/44—Oxidoreductases (1)
- A61K38/446—Superoxide dismutase (1.15)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/178—Oligonucleotides characterized by their use miRNA, siRNA or ncRNA
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biomedical Technology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Dermatology (AREA)
- Nutrition Science (AREA)
- Virology (AREA)
- Developmental Biology & Embryology (AREA)
- Endocrinology (AREA)
- Physiology (AREA)
- Psychology (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
Abstract
【選択図】なし
Description
(i)間質細胞由来因子1(CXCL12/SDF1)、スーパーオキシドジスムターゼ[Cu−Zn](SOD1)、中脳星状膠細胞由来神経栄養因子(MANF)、シスタチンC(CST3)、ガレクチン1(LGALS1)、グリア由来ネキシン(SERPINE2)、インスリン様成長因子II(IGF2)、潜在型トランスフォーミング成長因子ベータ結合タンパク質1(LTBP1)、潜在型トランスフォーミング成長因子ベータ結合タンパク質2(LTBP2)、潜在型トランスフォーミング成長因子ベータ結合タンパク質3フラグメント(LTBP3)、潜在型トランスフォーミング成長因子ベータ結合タンパク質4(LTBP4)、神経芽細胞分化関連タンパク質(AHNAK)および色素上皮由来因子(SERPINF1/PEDF)からなる群からの少なくとも1つのタンパク質;または
(ii)肝細胞成長因子(HGF)、胎盤成長因子(PIGF)、マクロファージコロニー刺激因子(MCSF)、血管内皮成長因子(VEGF)、顆粒球コロニー刺激因子(GCSF)、マクロファージ炎症性タンパク質3(MIP−3a)、成長調節発癌遺伝子アルファ(GRO−aもしくはCXCL1)、マクロファージ由来/CCL22ケモカイン(MDCもしくはCCL22)、成長調節発癌遺伝子(GRO)、IGFBP−2、ニューロトロフィン4(NT−4)、単球化学誘引物質タンパク質2(MCP−2/CCL8)、インスリン成長因子1(IGF−1)、顆粒球マクロファージコロニー刺激因子(GM−CSF)、インターロイキン2(IL−2)および脳由来神経栄養因子(BDNF)からなる群より選択される少なくとも1つのタンパク質;または
(iii)1SV、3SV、ACTG2、ADAM10、ADAMTSL1、ADM、ANXA4、APOD、CALM2、CD109、CD59、CDH6、CFD、COL15A1、COL1A2、COLEC12、CTHRC1、CTSC、CTSL、CXCL12、DCD、DDAH2、DKK1、DSG1、DSP、DSTN、ECH1、EDIL3、EFEMP1、ELN、FLG、GNB2、GREM2、H3F3B、HBA1、HIST1H2AH、HIST1H2BK、HIST1H4A、HMGN2、HNRNPAB、HSP90AA1、HSPA1A、HSPG2、IGFBP5、JUP、KHSRP、LDHA、MNB2、LTBP4、MAN1A1、MFAP4、MMP1、MMP14、MT2A、NBL1、OMD、PFN1、PI16、PSG5、PSMB6、PTGDS、RARRES2、SLIT3、SPOCK1、SPTBN4、STOM、TMSB10、TMSB4X、TNFAIP6、TNXB、TPI1、TUBA1C、UBC、VITおよびWNT5Aからなる群より選択される少なくとも1つのタンパク質;または
(iv)hsa−miR−4454+hsa−miR−7975、hsa−miR−23a−3p、hsa−let−7b−5p、hsa−miR−612、hsa−miR−125b−5p、hsa−miR−3144−3p、hsa−miR−199a−3p+hsa−miR−199b−3p、hsa−miR−191−5p、hsa−miR−100−5p、hsa−miR−127−3p、hsa−miR−1260a、hsa−miR−378h、hsa−miR−379−5p、hsa−miR−376a−3p、hsa−let−7i−5p、hsa−miR−526a+hsa−miR−518c−5p+hsa−miR−518d−5p、hsa−miR−212−3p、hsa−miR−520c−3p、hsa−miR−28−5p、hsa−miR−758−3p+hsa−miR−411−3p、hsa−miR−29a−3p、hsa−miR−1206、hsa−miR−1286、hsa−miR−514a−3p、hsa−miR−548ah−5p、hsa−miR−184、hsa−miR−543、hsa−miR−626、hsa−miR−339−3p、hsa−miR−1234−3p、hsa−miR−155−5p、hsa−miR−888−5p、hsa−miR−542−3p、hsa−miR−514b−5p、hsa−miR−548m、hsa−miR−30e−5pおよびhsa−miR−1290からなる群より選択される少なくとも1つのマイクロRNA(miRNA);あるいは
その組合せ
を含む。
i.外植または酵素消化によってhOMSCを単離する段階;
ii.hOMSCを培養培地中で拡大する段階;
iii.培地を基本培地に置き換える段階;
iv.hOMSCを基本培地中で1時間〜120時間の範囲の一定時間にわたって培養する段階;
v.培養物から培地を回収する段階;および
vi.任意選択で、培地を1.1〜10,000倍に濃縮する段階
を含む。
i.炎症性疾患(例えば、変形性関節症);
ii.自己免疫疾患(例えば、関節リウマチ、強皮症);
iii.血管疾患(例えば、動脈炎/バージャー病);
iv.心疾患(例えば、心筋梗塞、慢性心不全);
v.呼吸器系疾患(例えば、慢性閉塞性肺疾患、特発性肺線維症);
vi.骨格系疾患(例えば、骨再生、無血性壊死、骨髄炎、軟骨修復、腱修復、筋ジストロフィー);
vii.消化管疾患(例えば、瘻孔、潰瘍、食道狭窄、肝硬変、失禁、クローン病);
viii.腎疾患(例えば、腎障害);
ix.尿路(例えば、失禁);
x.皮膚疾患(例えば、足潰瘍、表皮水疱症、天疱瘡、糖尿病性潰瘍、静止静脈潰瘍、慢性褥瘡);
xi.老化関連疾患;
xii.末梢神経および骨格筋疾患(例えば、慢性炎症性脱髄性多発神経根ニューロパチー、ギラン・バレー症候群、筋ジストロフィー);
xiii.中枢神経系の疾患(例えば、神経変性疾患、例えば脱髄性疾患(多発性硬化症]、アルツハイマー病、パーキンソン病、球脊髄萎縮症など、脳卒中、脊髄虚血、多系統萎縮症としての自律神経系の疾患);
xiv.眼疾患(例えば、網膜症[加齢黄斑変性症、糖尿病性網膜症、動脈硬化性網膜症)、視神経炎);
xv.内分泌系の疾患(例えば、糖尿病およびその合併症:[血管障害、ニューロパチー、慢性潰瘍、腎障害]);ならびに
xvi.歯科口腔疾患(例えば、歯髄関連疾患、歯周病、歯槽骨欠損、免疫疾患を原因とする口腔粘膜潰瘍)
からなる群より選択される。
本発明は、疾患および障害の治療および予防のためのヒト口腔粘膜由来成体幹細胞のセクレトームを提供する。
口腔粘膜は、口腔、すなわち、歯肉および口蓋を含む頬および歯槽堤、舌、口腔底ならびに口唇の口腔部分を覆う粘膜である。口腔粘膜は、外胚葉起源の上皮組織と、外胚葉性間葉起源の結合組織である固有層(LP)とからなる。口腔内の結合組織が外胚葉性間葉起源であるのと同じように、口腔粘膜固有層(OMLP)の細胞は胚外胚葉性の神経堤を起源とする。ヒト口腔粘膜の創傷は主として再生により治癒する。治癒速度は皮膚またはその他の結合組織よりも速く、年齢および性別によって受ける影響はごくわずかであると思われる(Szpaderska,A.M.ら,J Dent Res,2003,82,621−626)。
2.
a.タンパク質
b.ペプチド
c.ホルモン
d.様々なDNAおよびRNA種
e.核酸のオリゴマー
f.分子量1,000ダルトン超のその他の分子
などの可溶性分子
3.
a.タンパク質:成長因子、サイトカイン、ホルモン、細胞表面受容体、細胞質タンパク質および核タンパク質、代謝酵素、受容体リガンド、接着タンパク質、エンドソーム関連タンパク質、テトラスパニン、脂質ラフト関連タンパク質、抗原など
b.RNA種:mRNA、miRNA、tRNA、rRNA、siRNAおよびlncRNAならびに考え得るその他のRNA種
c.DNA:ミトコンドリアDNA(mtDNA)、一本鎖DNA(ssDNA)、二本鎖DNA(dsDNA)
d.脂質:コレステロール、スフィンゴミエリン、ヘキソシルセルミド(hexosylcermide)およびその他
e.レクチン、グリカン、プロテオグリカン、糖タンパク質
を含有する細胞外小胞。
1.微小胞または脱落微小胞;大きさの範囲−50〜1500nm
2.エキソソーム;大きさの範囲−30〜120nm
3.小胞;大きさの範囲<500nm。
以下に記載する結果は、部分的には、口腔を覆う口腔粘膜の不可欠な部分であるヒト歯肉の固有層(上皮部分は含まない)に由来する細胞集団のセクレトームから得られたものである。口蓋および歯槽粘膜から単離したhOMSCは同じ特性を示す。
具体的には年齢25〜80歳のドナーの歯肉起源の口腔粘膜生検試料から、上および国際公開第2008/132722号に記載されている通りにhOMSCを入手した。
拡大培地で拡大し、累積集団倍加数が5〜80であるhOMSCの培養物をhOMSCセクレトームの生成に用いる。拡大培地を除去し、培養物をPBSで十分に洗浄し、次いで、基本培地またはLGDMEMを加える。24〜120時間後に、培地を収集し、遠心分離して死細胞をすべて除去する。上清はセクレトームを含む。
・化学的なもの:例えば、低酸素、高酸素、化学薬品、様々な種類の化学的刺激因子もしくは阻害剤または様々な経路、例えばCa++などの高イオンもしくは低イオン濃度および/またはグルコース、スタチン、ビスホスホナートのような様々な化学薬品など;
・物理的なもの:例えば、超音波、機械的振動、電気刺激、連続的または断続的な歪み、光、放射線;
・基質:例えば、接着タンパク質、三次元マトリックス、懸濁細胞培養用のビーズ;
・生物学的なもの:例えば、成長因子、サイトカイン、ホルモン刺激、分化因子、DNAおよびRNA種、遺伝的操作。
hOMSCを既に記載されている通りに入手した(Marynka−Kalmaniら,2010および国際公開第2008/132722号)。8日齢の乳児の包皮から酵素消化によって包皮SC(h皮膚SC)を単離した。両細胞型ともT−75細胞フラスコ中にて、必須アミノ酸、抗生物質およびウシ胎児血清を添加した低グルコースDMEMで増殖させた。
hOMSCセクレトームのタンパク質および核酸の内容を明らかにすることにより、hOMSCセクレトームに特有の特徴を確認する。3種類の異なる方法、すなわち、タンパク質アレイ、質量分光光度法(MS)およびマイクロRNA(miRNA)による特徴付けを用いて、広範囲にわたるhOMSCセクレトーム成分を得る。
hOMSCセクレトームのタンパク質の内容をMSおよびタンパク質アレイによって解析した。
1.試料10mlにTrizol(商標)試薬7mlを加え、ボルテックスする。次いで、試料を室温で5分間静置する。
2.クロロホルム1.4mlを加え、試料を15秒間、激しく振盪する。
3.試料を15,300G、4℃で15分間遠心分離する。
4.中間相を慎重に避けながら、上部の水相を新たなチューブに移す。
5.mirVana(商標)PARIS miRNA Isolation Kit(Ambion(登録商標))を製造業者のプロトコル通りに用いてmiRNAを単離する。mirVana(商標)キットは、連続する2つのGFFを用いる。無RNアーゼ水50μlでmiRNAを溶離させる。
逆転写も増幅も使用せずに、nCounter Reporter Probesと呼ばれる分子バーコードを用いることにより800種類のmiRNAを検出する方法であるnCounter miRNA Expression Assay(https://www.nanostring.comに記載される)を用いて、miRNA発現プロファイリングを実施した。特定のmiRNAカウント数を全実験試料で算出したCVS統計値に基づき選択した安定に発現するmiRNAに対して正規化するnSolver(商標)Software Analysis(NanoString Technologies社からの無料ダウンロード)を用いて、またはSpike−in対照を用いて、全データ解析および正規化を実施した。
糖尿病では、局所および全身のシグナル伝達の異常ならびに創傷治癒の合図に対する不適切な組織応答のため創傷治癒が遅れる。この創傷治癒過程の多因子性の異常は、細胞遊走の遅延、新たな血管および結合組織の形成の低下をもたらす。幹細胞はこれまで、その多因子性のセクレトームにより、最先端の糖尿病性創傷治療手段として提案されてきた。
hOMSCの治療効果が少なくとも部分的にはそれらの特有のセクレトームに起因するかどうかを検討するため、1×106個のhOMSCを無血清培地で24時間維持した。
・Antonyak MA,Cerionee RA(2015)Emerging picture of the distinct traits and functions of microvesicles and exosomes.PNAS 112(12),3589−3590.
・Baglio SR,Rooijers K,Koppers−Lalic D,.Verweij FJ,MP,Zini N,Naaijkens B,Perut F,Niessen HWM,Baldini N and Pegtel DM(2015).Human bone marrow−and adiposemesenchymal stem cells secrete exosomes enriched in distinctive miRNA and tRNA species.6,127−147.
・Desrochers LM,Antonyak MA,Cerione RA(2016)Extracellular vesicles:Satellites of information transfer in cancer and stem cell biology.Development Cell 37,301−309.
・DiPietro LA(2003).Differential injury responses in oral mucosal and cutaneous wounds.J.Dent.Res.82,621−626.
・Ganz J,Arie I,Ben−Zur T,Dadon−Nachum M,Pour S,Araidy S,Pitaru S,Offen D(2014).Astrocyte−like cells derived from human oral mucosa stem cells provide neuroprotection in vitro and in vivo.Stem Cells Transl.Med.3,375−86.
・Ganz J,Arie I,Buch S,Zur TB,Barhum Y,Pour S,Araidy S,Pitaru S,Offen D(2014).Dopaminergic−like neurons derived from oral mucosa stem cells by developmental cues improve symptoms in the hemi−parkinsonian rat model.PLoS One 9(6),e100445.
・Gue W.,Gao Y.,Li N.,Shao F.,Wang C.,Wang P.,Yang Z.,Li R.,and He J.(2017).Exosomes:New players in cancer(Review).Oncology Reports 38:665−675.
・Hu L,Wang J,Zhou X,Xiong Z,Zhao J,Yu R,Huang F,Zhang H,Chen L(2016).Exosomes derived from human adipose mesenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts.Scientific Reports 6,32993.
・Kanada M,Bachmann MH,Hardy JW,Frimannson DO,Bronsart L,Wang A,Sylvester MD,Schmidt TL,Kaspar RL,Butte MJ,Matin AC,Contag CH(2015).Differential fates of biomolecules delivered to target cells via extracellular vesicles.Proc.Natl.Acad.Sci.USA 112,E1433−E1442.
・Konala VB,Mamidi MK,Bhonde R,Das AK,Pochampally R,Pal R(2016).The current landscape of the mesenchymal stromal cell secretome:A new paradigm for cell−free regeneration.Cytotherapy 18(1),13−24.
・Lai,R.C.,Arslan,F.,Lee,M.M.,Sze,N.S.K.,Choo,A.,Chen,T.S.,Salto−Tellez,M.,Timmers,L.,Lee,C.N.,El Oakley,R.M.,et al.(2010).Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury.Stem Cell Res.4,214−222.
・Lopez−Verrilli MA,Caviedes A,Cabrera A,Sandoval S,Wyneken U,Khoury M(2016)Mesenchymal stem cell−derived exosomes from different sources selectively promote neuritic outgrowth.Neuroscience 320,129−139.
・Marynka−Kalmani K,Treves S,Yafee M,Rachima H,Gafni Y,Cohen MA,Pitaru S(2010).The lamina propria of adult human oral mucosa harbors a novel stem cell population.Stem Cells 28(5),984−95.
・Michaels J 5th,Churgin SS,Blechman KM,Greives MR,Aarabi S,Galiano RD,Gurtner GC(2007).db/db mice exhibit severe wound−healing impairments compared with other murine diabetic strains in a silicone−splinted excisional wound model.Wound Repair Regen.15(5),665−70
・Park CW,Kim KS,Bae S,Son HK,Myung PK,Hong HJ,Kim H(2009).Cytokine secretion profiling of human mesenchymal stem cells by antibody array.Int J Stem Cells 2(1),59−68.
・Rodrigues M,Wong VW,Rennert CR,Davis CR,Longaker MT,Gurtner GC(2015).Progenitor cell dysfunction underlie some diabetic complications.The American Journal of Pathology 2015,85(8).
・Skog J,Wurdinger T,van Rijn S,Meijer DH,Gainche L,Sena−Esteves M,Curry WT Jr,Carter BS,Krichevsky AM,Breakefield XO(2008).Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers.Nat.Cell.Biol.10(12),1470−6.
・Tachida Y,Sakurai H,Okutsu J,Suda K,Sugita R,Yaginuma Y,Ogura Y,Shimada K,Isono F,Kubota K and Kobayashi H.(2015).Proteomic Comparison of the Secreted Factors of Mesenchymal Stem Cells from Bone Marrow,Adipose Tissue and Dental Pulp.Journal of Proteomics and Bioinformatics;8(12),266−273.
・Tepper OM,Car J,’Robert J.Allen Jr,Chang CC,”Li CD,Tanaka R,Gupta SM,Levine JP,Saa deh PB,Warren SM.(2010).Decreased circulating cell number and failed mechanisms of stromal cell−derived factor−1・ mediated bone marrow mobilization impair diabetic tissue repair.Diabetes 59,1974−1983.
・Treves−Manusevitz S,Hoz L,Rachima H,Montoya G,Tzur E,Vardimon A,Narayanan AS,Amar S,Arzate H,Pitaru S(2013).Stem cells of the lamina propria of human oral mucosa and gingiva develop into mineralized tissues in vivo.J.Clin.Periodontol.40(1),73−81.
・Villarroya−Beltri C,Baixauli F,Gutierrez−Vazquez C,Sanchez−Madrid F,Mittelbrunn M(2014)Sorting it out:regulation of exosome loading.Semin Cancer Biol 28,3−3.
・Voutilainen MH,Arumae U,Airavaara M,Saarma M.(2015).Therapeutic potential of the endoplasmatic reticulum located and secreted CDNF/MANF family of neurotrophic factors in Parkinson’s Disease FEBS Letter 589,3739−3748.
・Wu Y.,Peng H.,Cui M.,Whitney N.P.,Huang Y.,and Zheng C.(2009),CXCL2 increases human neural progenitor cell proliferation through Akt−1/FOXO3a signaling pathway.Journal of Neurochemistry 109,1157−1167.
・Xu R,Greening DW,Zhu HJ,Takahashi N,Simpson RJ(2016).Extracellular vesicle isolation and characterization:toward clinical application.J,Clin,Invest.;126(4),1152−62.
・Zander C,Heidbreder M,Kasperek Y,Noll T,Seitz O,Saldamli B,Sudhoff H,Sader R,Kaltschmidt C,Kaltschmidt B(2009).Adult Palatum as a Novel Source of Neural Crest−Related Stem Cells.Stem Cells;27,1899−1910.
・Zhang Q,Nguyen P,Xu Q,Park W,Lee S,Furuhashi A,Le AD(2017).Neural Progenitor−Like Cells Induced from Human Gingiva−Derived Mesenchymal Stem Cells Regulate Myelination of Schwann Cells in Rat Sciatic Nerve Regeneration.Stem Cells Transl.Med.6(2),458−470.
Claims (47)
- 少なくとも1つの担体、賦形剤または希釈剤とともに、ヒト口腔粘膜幹細胞から分泌される物質(hOMSC由来セクレトーム)を含む、無細胞組成物。
- (i)間質細胞由来因子1(CXCL12/SDF1)、スーパーオキシドジスムターゼ[Cu−Zn](SOD1)、中脳星状膠細胞由来神経栄養因子(MANF)、シスタチンC(CST3)、ガレクチン1(LGALS1)、グリア由来ネキシン(SERPINE2)、インスリン様成長因子II(IGF2)、潜在型トランスフォーミング成長因子ベータ結合タンパク質1(LTBP1)、潜在型トランスフォーミング成長因子ベータ結合タンパク質2(LTBP2)、潜在型トランスフォーミング成長因子ベータ結合タンパク質3フラグメント(LTBP3)、潜在型トランスフォーミング成長因子ベータ結合タンパク質4(LTBP4)、神経芽細胞分化関連タンパク質(AHNAK)および色素上皮由来因子(SERPINF1/PEDF)からなる群からの少なくとも1つのタンパク質、または
(ii)肝細胞成長因子(HGF)、胎盤成長因子(PIGF)、マクロファージコロニー刺激因子(MCSF)、血管内皮成長因子(VEGF)、顆粒球コロニー刺激因子(GCSF)、マクロファージ炎症性タンパク質3(MIP−3a)、成長調節発癌遺伝子アルファ(GRO−aもしくはCXCL1)、マクロファージ由来/CCL22ケモカイン(MDCもしくはCCL22)、成長調節発癌遺伝子(GRO)、IGFBP−2、ニューロトロフィン4(NT−4)、単球化学誘引物質タンパク質2(MCP−2/CCL8)、インスリン成長因子1(IGF−1)、顆粒球マクロファージコロニー刺激因子(GM−CSF)、インターロイキン2(IL−2)および脳由来神経栄養因子(BDNF)からなる群より選択される少なくとも1つのタンパク質、または
(iii)1SV、3SV、ACTG2、ADAM10、ADAMTSL1、ADM、ANXA4、APOD、CALM2、CD109、CD59、CDH6、CFD、COL15A1、COL1A2、COLEC12、CTHRC1、CTSC、CTSL、CXCL12、DCD、DDAH2、DKK1、DSG1、DSP、DSTN、ECH1、EDIL3、EFEMP1、ELN、FLG、GNB2、GREM2、H3F3B、HBA1、HIST1H2AH、HIST1H2BK、HIST1H4A、HMGN2、HNRNPAB、HSP90AA1、HSPA1A、HSPG2、IGFBP5、JUP、KHSRP、LDHA、MNB2、LTBP4、MAN1A1、MFAP4、MMP1、MMP14、MT2A、NBL1、OMD、PFN1、PI16、PSG5、PSMB6、PTGDS、RARRES2、SLIT3、SPOCK1、SPTBN4、STOM、TMSB10、TMSB4X、TNFAIP6、TNXB、TPI1、TUBA1C、UBC、VITおよびWNT5Aからなる群より選択される少なくとも1つのタンパク質、または
(iv)hsa−miR−4454+hsa−miR−7975、hsa−miR−23a−3p、hsa−let−7b−5p、hsa−miR−612、hsa−miR−125b−5p、hsa−miR−3144−3p、hsa−miR−199a−3p+hsa−miR−199b−3p、hsa−miR−191−5p、hsa−miR−100−5p、hsa−miR−127−3p、hsa−miR−1260a、hsa−miR−378h、hsa−miR−379−5p、hsa−miR−376a−3p、hsa−let−7i−5p、hsa−miR−526a+hsa−miR−518c−5p+hsa−miR−518d−5p、hsa−miR−212−3p、hsa−miR−520c−3p、hsa−miR−28−5p、hsa−miR−758−3p+hsa−miR−411−3p、hsa−miR−29a−3p、hsa−miR−1206、hsa−miR−1286、hsa−miR−514a−3p、hsa−miR−548ah−5p、hsa−miR−184、hsa−miR−543、hsa−miR−626、hsa−miR−339−3p、hsa−miR−1234−3p、hsa−miR−155−5p、hsa−miR−888−5p、hsa−miR−542−3p、hsa−miR−514b−5p、hsa−miR−548m、hsa−miR−30e−5pおよびhsa−miR−1290からなる群より選択される少なくとも1つのマイクロRNA(miRNA)、あるいは
その組合せ
を含む、請求項1に記載の無細胞組成物。 - (i)、(ii)、(iii)または(iv)からの複数の物質を含む、請求項2に記載の無細胞組成物。
- 少なくとも1つの(i)からのタンパク質と、少なくとも1つの(ii)からのタンパク質と、少なくとも1つの(iii)のタンパク質と、任意選択で少なくとも1つの(iv)からのmiRNAとを含む、請求項2に記載の無細胞組成物。
- 間質細胞由来因子1(CXCL12/SDF1)、中脳星状膠細胞由来神経栄養因子(MANF)、スーパーオキシドジスムターゼ[Cu−Zn](SOD1)、肝細胞成長因子(HGF)、胎盤成長因子(PIGF)、マクロファージコロニー刺激因子(MCSF)および血管内皮成長因子(VEGF)からなる群より選択される少なくとも1つの因子を含む、請求項1〜4のいずれか1項に記載の無細胞組成物。
- hsa−miR−4454+hsa−miR−7975、hsa−miR−23a−3p、hsa−let−7b−5p、hsa−miR−612、hsa−miR−125b−5p、hsa−miR−3144−3p、hsa−miR−199a−3p+hsa−miR−199b−3p、hsa−miR−191−5p、hsa−miR−100−5p、hsa−miR−127−3p、hsa−miR−1260a、hsa−miR−378h、hsa−miR−379−5p、hsa−miR−376a−3p、hsa−let−7i−5p、hsa−miR−526a+hsa−miR−518c−5p+hsa−miR−518d−5p、hsa−miR−212−3p、hsa−miR−520c−3p、hsa−miR−28−5p、hsa−miR−758−3p+hsa−miR−411−3p、hsa−miR−29a−3p、hsa−miR−1206、hsa−miR−1286、hsa−miR−514a−3p、hsa−miR−548ah−5p、hsa−miR−184、hsa−miR−543、hsa−miR−626、hsa−miR−339−3p、hsa−miR−1234−3p、hsa−miR−155−5p、hsa−miR−888−5p、hsa−miR−542−3p、hsa−miR−514b−5p、hsa−miR−548m、hsa−miR−30e−5pおよびhsa−miR−1290からなる群より選択される少なくとも6つのマイクロRNA分子を含む、請求項1〜4のいずれか1項に記載の無細胞組成物。
- 前記少なくとも1つの(i)、(ii)または(iii)のタンパク質が、他の幹細胞源に由来するセクレトーム中より有意に高い濃度で存在する、請求項2〜5のいずれか1項に記載の無細胞組成物。
- 他の幹細胞源に由来するセクレトーム中より有意に高い濃度で存在する前記少なくとも1つのタンパク質が、間質細胞由来因子1(CXCL12/SDF1、P48061)、スーパーオキシドジスムターゼ[Cu−Zn](SOD1、P00441)、中脳星状膠細胞由来神経栄養因子(MANF、P55145)、肝細胞成長因子(HGF)、胎盤成長因子(PIGF)、マクロファージコロニー刺激因子(MCSF)、および血管内皮成長因子(VEGF)からなる群より選択される、請求項7に記載の無細胞組成物。
- 他の幹細胞源に由来するセクレトーム中より有意に低い濃度で少なくとも1つのタンパク質を含む、請求項1〜8のいずれか1項に記載の無細胞組成物。
- 前記少なくとも1つのタンパク質が、インターロイキン−8(IL−8)、ガンマインターフェロンによって誘導されるモノカイン(MIG/CXCL9)、インターロイキン6(IL−6)、Fms関連チロシンキナーゼ3リガンド(Flt−3リガンド)、レプチン、上皮由来好中球活性化ペプチド78(ENA−78/CXCL5)および単球走化性タンパク質3(MCP−3/CCL7)からなる群より選択される、請求項9に記載の無細胞組成物。
- 神経系のホメオスタシスに関与する少なくとも1つのタンパク質を含み、前記タンパク質が、シスタチンC、ガレクチン1、グリア由来ネキシン、インスリン様成長因子II、(IGF2)、潜在型トランスフォーミング成長因子ベータ結合タンパク質1(LTBP1)、潜在型トランスフォーミング成長因子ベータ結合タンパク質2(LTBP2);潜在型トランスフォーミング成長因子ベータ結合タンパク質3(LTBP3);潜在型トランスフォーミング成長因子ベータ結合タンパク質4(LTBP4);中脳星状膠細胞由来神経栄養因子(MANF)、神経芽細胞分化関連タンパク質(AHANK)、色素上皮由来因子(PEDF)、間質細胞由来因子1(SDF1)、およびスーパーオキシドジスムターゼ[Cu−Zn](SODC)からなる群より選択される、請求項1〜10のいずれか1項に記載の無細胞組成物。
- 細胞外小胞(EV)を含む、請求項1〜11のいずれか1項に記載の無細胞組成物。
- 微小胞を含む、請求項1〜12のいずれか1項に記載の無細胞組成物。
- エキソソームを含む、請求項1〜13のいずれか1項に記載の無細胞組成物。
- 1,000ダルトン以上の分子の大きさを有する可溶性因子を含む、請求項1〜14のいずれか1項に記載の無細胞組成物。
- 前記可溶性因子が、タンパク質、ペプチド、ホルモン、DNAおよびRNA種、オリゴヌクレオチドおよびポリヌクレオチド、ならびにその組合せからなる群より選択される、請求項15に記載の無細胞組成物。
- 可溶性因子と微小胞とエキソソームとを含む、請求項1〜16のいずれか1項に記載の無細胞組成物。
- 薬学的に許容される担体、賦形剤または希釈剤を含む医薬組成物である、請求項1〜17のいずれか1項に記載の組成物。
- 美容用組成物である、請求項1〜17のいずれか1項に記載の組成物。
- 疾患または障害を予防するまたは治療することにおける使用のための、請求項1〜19のいずれか1項に記載の組成物。
- 前記疾患または障害が、炎症性疾患;自己免疫疾患;血管疾患;心疾患;呼吸器系疾患;骨格系疾患;消化管疾患;腎疾患;尿路疾患;皮膚疾患;老化関連疾患;末梢神経疾患、骨格筋疾患;中枢神経系の疾患;眼疾患;内分泌系の疾患;および歯科口腔疾患からなる群より選択される、請求項20に記載の使用のための組成物。
- 組織リモデリング、組織修復または組織再生における使用のための、請求項1〜19のいずれか1項に記載の組成物。
- 組織リモデリング、組織修復または組織再生が、創傷治癒を促進すること、瘢痕形成を予防するまたは軽減すること;瘢痕治癒を促進すること、軟骨または骨形成を促進すること;中枢神経系または末梢神経系での損傷の修復または再生を促進すること;ならびに虚血器官の新血管新生および血管新生を促進することからなる群より選択される少なくとも1つの過程を含む、請求項22に記載の使用のための組成物。
- 前記損傷が、神経系の外傷、神経変性疾患または血管疾患により引き起こされた、請求項23に記載の使用のための組成物。
- 中枢神経系または末梢神経系での損傷の修復または再生を促進することにおける使用のための、薬学的に許容される担体、賦形剤または希釈剤と合わせた請求項11に記載の無細胞組成物。
- 前記セクレトームが、自家hOMSCに由来する、請求項1〜25のいずれか1項に記載の無細胞組成物。
- 前記セクレトームが、同種hOMSCに由来する、請求項1〜25のいずれか1項に記載の無細胞組成物。
- hOMSCから無細胞セクレトームを作製する方法であって、
i.外植または酵素消化によってhOMSCを単離する段階と、
ii.培養培地中でhOMSCを拡大する段階と、
iii.前記培地を基本培地に置き換える段階と、
iv.1時間〜120時間の範囲の一定時間にわたって前記基本培地中でhOMSCを培養する段階と
v.培養物から前記培地を回収する段階と、
vi.任意選択で、前記培地を1.1〜10,000倍に濃縮する段階
を含む、方法。 - 段階(iv)中にまたはその後に前記hOMSCが、前記セクレトームの内容に影響を及ぼす刺激または条件に供される、請求項28に記載の方法。
- それを必要とする対象に請求項1に記載の無細胞組成物を投与することを含む疾患または障害を予防するまたは治療する方法。
- 前記疾患または障害が、炎症性疾患;自己免疫疾患;血管疾患;心疾患;呼吸器系疾患;骨格系疾患;消化管疾患;腎疾患;尿路疾患;皮膚疾患;老化関連疾患;末梢神経および骨格筋疾患;中枢神経系の疾患;眼疾患;内分泌系の疾患;ならびに歯科口腔疾患からなる群より選択される、請求項30に記載の方法。
- 前記治療する方法が、組織リモデリング、組織修復または組織再生を含む、請求項30または31に記載の方法。
- 前記治療の方法が、少なくとも1つの医原性損傷によって全体にまたは部分的に破壊された器官および組織の修復または再生を含む、請求項30に記載の方法。
- 前記少なくとも1つの医原性損傷が、機械的外傷、化学的損傷、化学療法、放射線照射または熱により引き起こされる、請求項33に記載の方法。
- 前記少なくとも1つの損傷が、中枢神経系の挫傷、脊椎損傷、脊髄切断、末梢神経の挫滅または切断、熱傷、ニューロパチー、心臓病、骨折、腱および靭帯の断裂からなる群より選択される、請求項33に記載の方法。
- 組織リモデリング、組織修復または組織再生が、創傷治癒を促進すること、瘢痕形成を予防するまたは軽減すること、瘢痕治癒を促進するまたは軟骨もしくは骨形成を促進すること;外傷、神経変性疾患または神経系の血管疾患により引き起こされる中枢神経系または末梢神経系の修復または再生を促進すること;および虚血器官の新血管新生および血管新生を促進することからなる群より選択される少なくとも1つの過程を含む、請求項32に記載の方法。
- 前記虚血器官が、心臓、脳、末梢神経および腎臓からなる群より選択される、請求項36に記載の方法。
- 前記組成物が、医薬組成物である、請求項30に記載の方法。
- 前記組成物が、美容用組成物である、請求項30に記載の方法。
- 前記障害が、糖尿病性創傷である、請求項30に記載の方法。
- 前記障害が、美容障害である、請求項39に記載の方法。
- 前記無細胞組成物が、自家hOMSCに由来するセクレトームを含む、請求項30〜41のいずれか1項に記載の方法。
- 前記無細胞組成物が、同種hOMSCに由来するセクレトームを含む、請求項30〜41のいずれか1項に記載の方法。
- 前記組成物が、局所、皮下、筋肉内、動脈内、腹腔内、髄腔内、静脈内からなる群より選択される経路によりそれを必要とする対象に投与されるか必要とする部位で任意の組織中に直接注射される、請求項30〜43のいずれか1項に記載の方法。
- 前記組成物が、損傷組織に局所的に投与される、請求項30〜43のいずれか1項に記載の方法。
- 前記組成物が、全身的に投与される、請求項30〜43のいずれか1項に記載の方法。
- 前記hOMSCが、ナイーブ細胞である、請求項1〜19のいずれか1項に記載の無細胞組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201762533056P | 2017-07-16 | 2017-07-16 | |
US62/533,056 | 2017-07-16 | ||
PCT/IL2018/050783 WO2019016799A1 (en) | 2017-07-16 | 2018-07-16 | SECRETEOME OF HUMAN MUCOSAL MUCOSAL STEM CELLS |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2020527038A true JP2020527038A (ja) | 2020-09-03 |
JP2020527038A5 JP2020527038A5 (ja) | 2021-08-12 |
Family
ID=65016592
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020501135A Pending JP2020527038A (ja) | 2017-07-16 | 2018-07-16 | ヒト口腔粘膜幹細胞セクレトーム |
Country Status (7)
Country | Link |
---|---|
US (2) | US20200155612A1 (ja) |
EP (1) | EP3655525A4 (ja) |
JP (1) | JP2020527038A (ja) |
KR (1) | KR20200029475A (ja) |
CN (1) | CN111093681A (ja) |
CA (1) | CA3067691A1 (ja) |
WO (1) | WO2019016799A1 (ja) |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20210005031A (ko) | 2018-03-29 | 2021-01-13 | 테크니온 리서치 엔드 디벨로프먼트 화운데이션 엘티디. | Pten 억제제를 포함하는 소포 및 이의 용도 |
US20210386827A1 (en) * | 2018-10-15 | 2021-12-16 | Avery Therapeutics, Inc. | Cell-free compositions and methods for restoration or enhancement of tissue function |
CN109517772A (zh) * | 2018-10-30 | 2019-03-26 | 南昌大学 | 一种乳酸乳球菌mg1363的构建及其在治疗产妇乳头皲裂中的应用 |
US10881693B2 (en) | 2019-04-09 | 2021-01-05 | Combangio, Inc. | Processes for making and using a mesenchymal stem cell derived secretome |
CN111254114B (zh) * | 2020-03-24 | 2021-12-07 | 山东兴瑞生物科技有限公司 | 一种人口腔黏膜干细胞转化成星形胶质细胞的培养方法 |
IT202000017746A1 (it) * | 2020-07-22 | 2022-01-22 | ALGO BIOTECHNOLOGIES srl | Composizione farmaceutica comprendente mezzo condizionato da secretoma di cellule mesenchimali del cavo orale |
CN112190592B (zh) * | 2020-08-25 | 2022-03-11 | 苏州市立医院(北区) | miRNA在制备防治骨关节炎药物的应用、miRNA高表达的外泌体和应用 |
CN112143708B (zh) * | 2020-10-12 | 2024-05-24 | 江苏芯超生物科技(集团)有限公司 | 一种脐带间充质干细胞、干细胞精华因子和在抗皮肤衰老方面的应用 |
WO2022086276A1 (ko) * | 2020-10-22 | 2022-04-28 | 가톨릭대학교 산학협력단 | 특정 유전자의 발현이 증가 또는 감소된 줄기세포를 유효성분으로 포함하는 류마티스 관절염 예방 또는 치료용 약학적 조성물 |
KR20240070501A (ko) | 2021-07-02 | 2024-05-21 | 컴반지오, 인크. | 세포 피브로넥틴 조성물의 제조 및 사용 방법 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2011513217A (ja) * | 2008-02-22 | 2011-04-28 | エイジェンシー・フォー・サイエンス,テクノロジー・アンド・リサーチ(エイ・スター) | 間葉系幹細胞粒子 |
WO2015052527A1 (en) * | 2013-10-09 | 2015-04-16 | Reneuron Limited | Microparticles, mirna and wound therapy |
US20160324898A1 (en) * | 2015-05-04 | 2016-11-10 | Stemedica International, Sa | Compositions and methods for the treatment of alzheimer's disease |
WO2017001649A1 (en) * | 2015-07-02 | 2017-01-05 | Med Cell Europe Ag | Secretomes and method for producing secretomes |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007027156A1 (en) * | 2005-09-02 | 2007-03-08 | Agency For Science, Technology And Research | Method of deriving mesenchymal stem cells |
WO2013076726A1 (en) * | 2011-11-21 | 2013-05-30 | Ramot At Tel-Aviv University Ltd. | Stem cell-derived neural cells for cell therapy in neurological disorders |
US10772911B2 (en) * | 2013-12-20 | 2020-09-15 | Advanced ReGen Medical Technologies, LLC | Cell free compositions for cellular restoration and methods of making and using same |
-
2018
- 2018-07-16 EP EP18835719.8A patent/EP3655525A4/en active Pending
- 2018-07-16 JP JP2020501135A patent/JP2020527038A/ja active Pending
- 2018-07-16 CN CN201880059874.0A patent/CN111093681A/zh active Pending
- 2018-07-16 WO PCT/IL2018/050783 patent/WO2019016799A1/en unknown
- 2018-07-16 CA CA3067691A patent/CA3067691A1/en active Pending
- 2018-07-16 US US16/630,954 patent/US20200155612A1/en not_active Abandoned
- 2018-07-16 KR KR1020207001660A patent/KR20200029475A/ko not_active Application Discontinuation
-
2023
- 2023-08-07 US US18/366,403 patent/US20230416745A1/en active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2011513217A (ja) * | 2008-02-22 | 2011-04-28 | エイジェンシー・フォー・サイエンス,テクノロジー・アンド・リサーチ(エイ・スター) | 間葉系幹細胞粒子 |
WO2015052527A1 (en) * | 2013-10-09 | 2015-04-16 | Reneuron Limited | Microparticles, mirna and wound therapy |
US20160324898A1 (en) * | 2015-05-04 | 2016-11-10 | Stemedica International, Sa | Compositions and methods for the treatment of alzheimer's disease |
WO2017001649A1 (en) * | 2015-07-02 | 2017-01-05 | Med Cell Europe Ag | Secretomes and method for producing secretomes |
Non-Patent Citations (2)
Title |
---|
GANZ J., ET AL.: "Dopaminergic-like neurons derived from oral mucosa stem cells by developmental cues improve symptoms", PLOS ONE, vol. 9(6), JPN6022023791, 19 June 2014 (2014-06-19), pages 100445, ISSN: 0005027558 * |
MARYNKA-KALMANI K., ET AL.: "The lamina propria of adult human oral mucosa harbors a novel stem cell population.", STEMCELLS, vol. 28(5), JPN6022023790, May 2010 (2010-05-01), pages 984 - 95, ISSN: 0005027559 * |
Also Published As
Publication number | Publication date |
---|---|
EP3655525A4 (en) | 2021-04-21 |
CA3067691A1 (en) | 2019-01-24 |
CN111093681A (zh) | 2020-05-01 |
US20230416745A1 (en) | 2023-12-28 |
WO2019016799A1 (en) | 2019-01-24 |
EP3655525A1 (en) | 2020-05-27 |
US20200155612A1 (en) | 2020-05-21 |
KR20200029475A (ko) | 2020-03-18 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2020527038A (ja) | ヒト口腔粘膜幹細胞セクレトーム | |
JP6644851B2 (ja) | 幹細胞微粒子 | |
Gu et al. | Transplantation of bone marrow mesenchymal stem cells reduces lesion volume and induces axonal regrowth of injured spinal cord | |
JP2016513095A (ja) | 幹細胞微粒子及びmiRNA | |
JP2015529450A (ja) | 幹細胞微粒子 | |
JP2016507550A (ja) | 微粒子の製造方法 | |
KR20160035087A (ko) | 줄기 세포 마이크로입자 및 miRNA | |
Liu et al. | Therapeutic prospects of MicroRNAs carried by mesenchymal stem cells-derived extracellular vesicles in autoimmune diseases | |
US20130058903A1 (en) | Stem-Cell Material and Method of Use | |
Sun et al. | Sequential paracrine mechanisms are necessary for the therapeutic benefits of stem cell therapy | |
Chen et al. | Aging and mesenchymal stem cells: therapeutic opportunities and challenges in the older group | |
Kim et al. | Exosome-mediated bidirectional signaling between mesenchymal stem cells and chondrocytes for enhanced chondrogenesis | |
Lai et al. | VEGF promotes tendon regeneration of aged rats by inhibiting adipogenic differentiation of tendon stem/progenitor cells and promoting vascularization | |
Bavarsad et al. | TGFβ1-pretreated exosomes of Wharton jelly mesenchymal stem cell as a therapeutic strategy for improving liver fibrosis | |
Wang et al. | Emerging roles of circular RNAs in stem cells | |
EP4379045A1 (en) | Method for producing highly proliferative cell, and highly proliferative cell and use thereof | |
Liu et al. | Emerging role of mesenchymal stem cell-derived extracellular vesicles in oral and craniomaxillofacial tissue regenerative medicine | |
US20200397825A1 (en) | Compositions and methods for treating age-related macular degeneration | |
Hao et al. | Biological Cardiac Patch Based on Extracellular Vesicles and Extracellular Matrix for Regulating Injury-Related Microenvironment and Promoting Cardiac Tissue Recovery | |
Divband et al. | Human Umbilical Cord Mesenchymal Stem Cells-Derived Small Extracellular Vesicles Can Be Considered as Cell-Free Therapeutics for Angiogenesis Promotion | |
RU2803286C1 (ru) | Композиция для нейропротекции и стимуляции нейрорегенерации головного мозга после повреждения, средство на ее основе, способ его получения и применения | |
EP4173629A1 (en) | Cranial nerve disorder therapeutic agent including culture supernatant of tissue cells derived from fetal appendage | |
EP4173631A1 (en) | Cranial neuropathy therapeutic agent containing culture supernatant for umbilical cord blood monocytic cells | |
Uzieliene et al. | Menstrual Blood-Derived Mesenchymal Stem Cell Paracrine Factors Stimulate Chondrogenesis in vitro and Possess Protective Effects to Articular Cartilage | |
JP2024079909A (ja) | 高増殖性細胞、その製造方法、およびその用途 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210629 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20210629 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220614 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20220822 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20221208 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230404 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20230602 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20230807 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20231003 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20240109 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20240408 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20240625 |