EA035360B1 - Способы трансдифференцировки и способы их использования - Google Patents
Способы трансдифференцировки и способы их использования Download PDFInfo
- Publication number
- EA035360B1 EA035360B1 EA201791508A EA201791508A EA035360B1 EA 035360 B1 EA035360 B1 EA 035360B1 EA 201791508 A EA201791508 A EA 201791508A EA 201791508 A EA201791508 A EA 201791508A EA 035360 B1 EA035360 B1 EA 035360B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- cells
- expression
- cell
- insulin
- another embodiment
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 201
- 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 abstract description 328
- 108090001061 Insulin Proteins 0.000 claims abstract description 167
- 229940125396 insulin Drugs 0.000 claims abstract description 165
- 102000004877 Insulin Human genes 0.000 claims abstract description 164
- 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 claims abstract description 141
- 239000008103 glucose Substances 0.000 claims abstract description 139
- 230000001105 regulatory effect Effects 0.000 claims abstract description 68
- 230000001965 increasing effect Effects 0.000 claims abstract description 54
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 claims abstract description 40
- 101000976075 Homo sapiens Insulin Proteins 0.000 claims abstract description 39
- 238000004519 manufacturing process Methods 0.000 claims abstract description 33
- 230000028327 secretion Effects 0.000 claims abstract description 30
- 210000004027 cell Anatomy 0.000 claims description 1036
- 230000014509 gene expression Effects 0.000 claims description 238
- 102100041030 Pancreas/duodenum homeobox protein 1 Human genes 0.000 claims description 134
- 210000005229 liver cell Anatomy 0.000 claims description 132
- 101710144033 Pancreas/duodenum homeobox protein 1 Proteins 0.000 claims description 117
- 150000007523 nucleic acids Chemical class 0.000 claims description 111
- 102000040945 Transcription factor Human genes 0.000 claims description 106
- 108091023040 Transcription factor Proteins 0.000 claims description 106
- 102000039446 nucleic acids Human genes 0.000 claims description 105
- 108020004707 nucleic acids Proteins 0.000 claims description 105
- 230000003914 insulin secretion Effects 0.000 claims description 75
- 208000015181 infectious disease Diseases 0.000 claims description 61
- 239000013598 vector Substances 0.000 claims description 59
- 239000013604 expression vector Substances 0.000 claims description 47
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 43
- 102000005396 glutamine synthetase Human genes 0.000 claims description 41
- 108020002326 glutamine synthetase Proteins 0.000 claims description 41
- 101150075928 Pax4 gene Proteins 0.000 claims description 39
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 39
- 229920001184 polypeptide Polymers 0.000 claims description 37
- 210000001519 tissue Anatomy 0.000 claims description 36
- 210000004185 liver Anatomy 0.000 claims description 35
- 230000004913 activation Effects 0.000 claims description 32
- 108060003199 Glucagon Proteins 0.000 claims description 31
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 claims description 27
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 27
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 claims description 27
- 229960004666 glucagon Drugs 0.000 claims description 27
- 229910052744 lithium Inorganic materials 0.000 claims description 27
- 210000005228 liver tissue Anatomy 0.000 claims description 27
- VOUAQYXWVJDEQY-QENPJCQMSA-N 33017-11-7 Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)NCC(=O)NCC(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)CCC1 VOUAQYXWVJDEQY-QENPJCQMSA-N 0.000 claims description 24
- 238000012545 processing Methods 0.000 claims description 24
- 108010075254 C-Peptide Proteins 0.000 claims description 22
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 17
- 230000004156 Wnt signaling pathway Effects 0.000 claims description 17
- 210000002901 mesenchymal stem cell Anatomy 0.000 claims description 17
- 230000003247 decreasing effect Effects 0.000 claims description 16
- 230000001537 neural effect Effects 0.000 claims description 16
- 230000005014 ectopic expression Effects 0.000 claims description 9
- 102100037241 Endoglin Human genes 0.000 claims description 8
- 101000881679 Homo sapiens Endoglin Proteins 0.000 claims description 8
- 210000003958 hematopoietic stem cell Anatomy 0.000 claims description 8
- 210000003494 hepatocyte Anatomy 0.000 claims description 8
- 230000006698 induction Effects 0.000 claims description 8
- 102100022464 5'-nucleotidase Human genes 0.000 claims description 7
- 101000678236 Homo sapiens 5'-nucleotidase Proteins 0.000 claims description 7
- 101000578254 Homo sapiens Homeobox protein Nkx-6.1 Proteins 0.000 claims description 7
- 101000800116 Homo sapiens Thy-1 membrane glycoprotein Proteins 0.000 claims description 7
- 108091027981 Response element Proteins 0.000 claims description 7
- 102100033523 Thy-1 membrane glycoprotein Human genes 0.000 claims description 7
- 210000002919 epithelial cell Anatomy 0.000 claims description 7
- 102100025422 Bone morphogenetic protein receptor type-2 Human genes 0.000 claims description 6
- 101000994375 Homo sapiens Integrin alpha-4 Proteins 0.000 claims description 6
- 101000955481 Homo sapiens Phosphatidylcholine translocator ABCB4 Proteins 0.000 claims description 6
- 102100032818 Integrin alpha-4 Human genes 0.000 claims description 6
- 102100039032 Phosphatidylcholine translocator ABCB4 Human genes 0.000 claims description 6
- 102100036034 Thrombospondin-1 Human genes 0.000 claims description 6
- 210000005260 human cell Anatomy 0.000 claims description 6
- 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 claims description 5
- 102100034452 Alternative prion protein Human genes 0.000 claims description 5
- 102100032912 CD44 antigen Human genes 0.000 claims description 5
- 101000924727 Homo sapiens Alternative prion protein Proteins 0.000 claims description 5
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 claims description 5
- 101000994365 Homo sapiens Integrin alpha-6 Proteins 0.000 claims description 5
- 101000573901 Homo sapiens Major prion protein Proteins 0.000 claims description 5
- 101000612089 Homo sapiens Pancreas/duodenum homeobox protein 1 Proteins 0.000 claims description 5
- 210000002950 fibroblast Anatomy 0.000 claims description 5
- 101000659879 Homo sapiens Thrombospondin-1 Proteins 0.000 claims description 4
- 102100032816 Integrin alpha-6 Human genes 0.000 claims description 4
- 210000000577 adipose tissue Anatomy 0.000 claims description 4
- 210000001185 bone marrow Anatomy 0.000 claims description 4
- 210000002889 endothelial cell Anatomy 0.000 claims description 4
- 210000002826 placenta Anatomy 0.000 claims description 4
- 210000003491 skin Anatomy 0.000 claims description 4
- 210000003954 umbilical cord Anatomy 0.000 claims description 4
- 102100028098 Homeobox protein Nkx-6.1 Human genes 0.000 claims description 3
- 208000016222 Pancreatic disease Diseases 0.000 claims description 3
- 102000027316 Vesicle-associated membrane protein 4 Human genes 0.000 claims description 3
- 108091013883 Vesicle-associated membrane protein 4 Proteins 0.000 claims description 3
- 210000000601 blood cell Anatomy 0.000 claims description 3
- 210000001671 embryonic stem cell Anatomy 0.000 claims description 3
- 230000002708 enhancing effect Effects 0.000 claims description 3
- 210000004700 fetal blood Anatomy 0.000 claims description 3
- 108010046722 Thrombospondin 1 Proteins 0.000 claims description 2
- 210000003897 hepatic stem cell Anatomy 0.000 claims description 2
- 235000015110 jellies Nutrition 0.000 claims description 2
- 239000008274 jelly Substances 0.000 claims description 2
- 210000000663 muscle cell Anatomy 0.000 claims description 2
- 208000024691 pancreas disease Diseases 0.000 claims description 2
- 210000004991 placental stem cell Anatomy 0.000 claims description 2
- 210000004927 skin cell Anatomy 0.000 claims description 2
- 210000004748 cultured cell Anatomy 0.000 claims 3
- 108050008407 Bone morphogenetic protein receptor type-2 Proteins 0.000 claims 2
- 102100025222 CD63 antigen Human genes 0.000 claims 2
- 102100023607 Homer protein homolog 1 Human genes 0.000 claims 2
- 101001017818 Homo sapiens ATP-dependent translocase ABCB1 Proteins 0.000 claims 2
- 108010009489 Lysosomal-Associated Membrane Protein 3 Proteins 0.000 claims 2
- 102400000321 Glucagon Human genes 0.000 claims 1
- 101710147597 Homer protein homolog 1 Proteins 0.000 claims 1
- 101001048469 Homo sapiens Homer protein homolog 1 Proteins 0.000 claims 1
- 108091000054 Prion Proteins 0.000 claims 1
- 102000029797 Prion Human genes 0.000 claims 1
- 210000002798 bone marrow cell Anatomy 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 210000004989 spleen cell Anatomy 0.000 claims 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 137
- 101100129232 Danio rerio mafaa gene Proteins 0.000 description 114
- 101150051019 Klrg1 gene Proteins 0.000 description 114
- 101150084866 MAFA gene Proteins 0.000 description 114
- 108090000623 proteins and genes Proteins 0.000 description 95
- 238000011282 treatment Methods 0.000 description 76
- 238000003306 harvesting Methods 0.000 description 58
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 54
- 230000008569 process Effects 0.000 description 46
- 108010056088 Somatostatin Proteins 0.000 description 44
- 238000002474 experimental method Methods 0.000 description 42
- 101100351017 Mus musculus Pax4 gene Proteins 0.000 description 39
- 101710164463 Preterminal protein Proteins 0.000 description 39
- 230000006870 function Effects 0.000 description 39
- 102000004169 proteins and genes Human genes 0.000 description 38
- 230000004044 response Effects 0.000 description 38
- 102000005157 Somatostatin Human genes 0.000 description 37
- 210000000496 pancreas Anatomy 0.000 description 36
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 36
- 229960000553 somatostatin Drugs 0.000 description 36
- 235000018102 proteins Nutrition 0.000 description 35
- 230000035899 viability Effects 0.000 description 33
- 230000000694 effects Effects 0.000 description 32
- 102000053602 DNA Human genes 0.000 description 31
- 108020004414 DNA Proteins 0.000 description 31
- 241000700605 Viruses Species 0.000 description 31
- 101100519293 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pdx-1 gene Proteins 0.000 description 30
- 102100024392 Insulin gene enhancer protein ISL-1 Human genes 0.000 description 29
- 206010012601 diabetes mellitus Diseases 0.000 description 29
- 230000035800 maturation Effects 0.000 description 29
- -1 NeuroDl Proteins 0.000 description 28
- 241000701161 unidentified adenovirus Species 0.000 description 28
- 102000051325 Glucagon Human genes 0.000 description 27
- 238000010899 nucleation Methods 0.000 description 27
- 101100096242 Mus musculus Sox9 gene Proteins 0.000 description 25
- 102000052651 Pancreatic hormone Human genes 0.000 description 23
- 239000000203 mixture Substances 0.000 description 23
- 239000004025 pancreas hormone Substances 0.000 description 23
- 229940032957 pancreatic hormone Drugs 0.000 description 23
- 108050003627 Wnt Proteins 0.000 description 22
- 102000013814 Wnt Human genes 0.000 description 22
- 101000613495 Homo sapiens Paired box protein Pax-4 Proteins 0.000 description 21
- 150000001875 compounds Chemical class 0.000 description 21
- 230000007423 decrease Effects 0.000 description 21
- 239000003814 drug Substances 0.000 description 21
- 102100040909 Paired box protein Pax-4 Human genes 0.000 description 20
- 238000004458 analytical method Methods 0.000 description 20
- 238000000338 in vitro Methods 0.000 description 20
- 101150070110 Isl1 gene Proteins 0.000 description 17
- 210000004962 mammalian cell Anatomy 0.000 description 17
- 230000011664 signaling Effects 0.000 description 17
- 229940124597 therapeutic agent Drugs 0.000 description 17
- 101710183548 Pyridoxal 5'-phosphate synthase subunit PdxS Proteins 0.000 description 16
- 230000007717 exclusion Effects 0.000 description 16
- 238000003127 radioimmunoassay Methods 0.000 description 16
- 238000003757 reverse transcription PCR Methods 0.000 description 16
- 108091006299 SLC2A2 Proteins 0.000 description 15
- 229920002477 rna polymer Polymers 0.000 description 15
- 108010088751 Albumins Proteins 0.000 description 14
- 102000009027 Albumins Human genes 0.000 description 14
- 239000003795 chemical substances by application Substances 0.000 description 14
- 230000001225 therapeutic effect Effects 0.000 description 14
- 108060000903 Beta-catenin Proteins 0.000 description 13
- 102000015735 Beta-catenin Human genes 0.000 description 13
- 102000015395 alpha 1-Antitrypsin Human genes 0.000 description 13
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 13
- 229940024142 alpha 1-antitrypsin Drugs 0.000 description 13
- 238000003556 assay Methods 0.000 description 13
- 230000003833 cell viability Effects 0.000 description 13
- 239000000523 sample Substances 0.000 description 13
- 108010085238 Actins Proteins 0.000 description 12
- 101001053263 Homo sapiens Insulin gene enhancer protein ISL-1 Proteins 0.000 description 12
- 108700020479 Pancreatic hormone Proteins 0.000 description 12
- 239000002299 complementary DNA Substances 0.000 description 12
- 230000018109 developmental process Effects 0.000 description 12
- 238000001415 gene therapy Methods 0.000 description 12
- 238000011534 incubation Methods 0.000 description 12
- 108020004999 messenger RNA Proteins 0.000 description 12
- 230000007170 pathology Effects 0.000 description 12
- 238000001890 transfection Methods 0.000 description 12
- 101800001268 Pancreatic hormone Proteins 0.000 description 11
- 238000004113 cell culture Methods 0.000 description 11
- 238000001727 in vivo Methods 0.000 description 11
- 238000002347 injection Methods 0.000 description 11
- 239000007924 injection Substances 0.000 description 11
- 239000000463 material Substances 0.000 description 11
- 239000013603 viral vector Substances 0.000 description 11
- 102100022900 Actin, cytoplasmic 1 Human genes 0.000 description 10
- 206010033645 Pancreatitis Diseases 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 238000002659 cell therapy Methods 0.000 description 10
- 238000004520 electroporation Methods 0.000 description 10
- 239000012634 fragment Substances 0.000 description 10
- 239000005090 green fluorescent protein Substances 0.000 description 10
- 229940088597 hormone Drugs 0.000 description 10
- 239000005556 hormone Substances 0.000 description 10
- 230000001939 inductive effect Effects 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 238000002560 therapeutic procedure Methods 0.000 description 10
- 102100037732 Neuroendocrine convertase 2 Human genes 0.000 description 9
- 101150106167 SOX9 gene Proteins 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 9
- 239000008280 blood Substances 0.000 description 9
- 238000005516 engineering process Methods 0.000 description 9
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 9
- 201000001421 hyperglycemia Diseases 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- 210000002569 neuron Anatomy 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 8
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 8
- 230000003213 activating effect Effects 0.000 description 8
- 150000001413 amino acids Chemical class 0.000 description 8
- 238000001574 biopsy Methods 0.000 description 8
- 238000011161 development Methods 0.000 description 8
- 230000004069 differentiation Effects 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 238000000605 extraction Methods 0.000 description 8
- 230000002440 hepatic effect Effects 0.000 description 8
- 239000002502 liposome Substances 0.000 description 8
- 238000003259 recombinant expression Methods 0.000 description 8
- 210000000130 stem cell Anatomy 0.000 description 8
- 230000003612 virological effect Effects 0.000 description 8
- 102100034540 Adenomatous polyposis coli protein Human genes 0.000 description 7
- 101000924577 Homo sapiens Adenomatous polyposis coli protein Proteins 0.000 description 7
- 108091028043 Nucleic acid sequence Proteins 0.000 description 7
- 208000036142 Viral infection Diseases 0.000 description 7
- 238000001514 detection method Methods 0.000 description 7
- 238000010586 diagram Methods 0.000 description 7
- 239000003937 drug carrier Substances 0.000 description 7
- 210000004153 islets of langerhan Anatomy 0.000 description 7
- 230000001404 mediated effect Effects 0.000 description 7
- 230000008672 reprogramming Effects 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 238000013518 transcription Methods 0.000 description 7
- 230000035897 transcription Effects 0.000 description 7
- 238000012546 transfer Methods 0.000 description 7
- 230000001052 transient effect Effects 0.000 description 7
- 230000009385 viral infection Effects 0.000 description 7
- 102100037985 Dickkopf-related protein 3 Human genes 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- 241000588724 Escherichia coli Species 0.000 description 6
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 6
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 6
- 101000951342 Homo sapiens Dickkopf-related protein 3 Proteins 0.000 description 6
- 101000601394 Homo sapiens Neuroendocrine convertase 2 Proteins 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 230000000735 allogeneic effect Effects 0.000 description 6
- 230000000692 anti-sense effect Effects 0.000 description 6
- 230000027455 binding Effects 0.000 description 6
- 230000033228 biological regulation Effects 0.000 description 6
- 230000010261 cell growth Effects 0.000 description 6
- 230000001413 cellular effect Effects 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 6
- 229940088598 enzyme Drugs 0.000 description 6
- 238000002955 isolation Methods 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- 230000035755 proliferation Effects 0.000 description 6
- 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 6
- 208000024891 symptom Diseases 0.000 description 6
- 210000003462 vein Anatomy 0.000 description 6
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 5
- 238000002965 ELISA Methods 0.000 description 5
- 101000971533 Homo sapiens Killer cell lectin-like receptor subfamily G member 1 Proteins 0.000 description 5
- 101000979205 Homo sapiens Transcription factor MafA Proteins 0.000 description 5
- 239000005089 Luciferase Substances 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 241000283973 Oryctolagus cuniculus Species 0.000 description 5
- 102100023237 Transcription factor MafA Human genes 0.000 description 5
- 108090000631 Trypsin Proteins 0.000 description 5
- 102000004142 Trypsin Human genes 0.000 description 5
- 239000003242 anti bacterial agent Substances 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 238000009395 breeding Methods 0.000 description 5
- 230000001488 breeding effect Effects 0.000 description 5
- 230000004663 cell proliferation Effects 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 230000001747 exhibiting effect Effects 0.000 description 5
- 239000012091 fetal bovine serum Substances 0.000 description 5
- 239000001963 growth medium Substances 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- OGQSCIYDJSNCMY-UHFFFAOYSA-H iron(3+);methyl-dioxido-oxo-$l^{5}-arsane Chemical compound [Fe+3].[Fe+3].C[As]([O-])([O-])=O.C[As]([O-])([O-])=O.C[As]([O-])([O-])=O OGQSCIYDJSNCMY-UHFFFAOYSA-H 0.000 description 5
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 5
- 239000003550 marker Substances 0.000 description 5
- 239000011859 microparticle Substances 0.000 description 5
- 125000003729 nucleotide group Chemical group 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 230000004203 pancreatic function Effects 0.000 description 5
- 239000013612 plasmid Substances 0.000 description 5
- 238000003908 quality control method Methods 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 230000003248 secreting effect Effects 0.000 description 5
- 230000003068 static effect Effects 0.000 description 5
- 230000004936 stimulating effect Effects 0.000 description 5
- 238000003860 storage Methods 0.000 description 5
- 238000001356 surgical procedure Methods 0.000 description 5
- 230000008685 targeting Effects 0.000 description 5
- 238000010361 transduction Methods 0.000 description 5
- 230000026683 transduction Effects 0.000 description 5
- 239000012588 trypsin Substances 0.000 description 5
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 108010011459 Exenatide Proteins 0.000 description 4
- 102000030595 Glucokinase Human genes 0.000 description 4
- 108010021582 Glucokinase Proteins 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 241000238631 Hexapoda Species 0.000 description 4
- 101000934635 Homo sapiens Bone morphogenetic protein receptor type-2 Proteins 0.000 description 4
- 101000923090 Homo sapiens Homeobox protein ARX Proteins 0.000 description 4
- 101000604998 Homo sapiens Lysosome-associated membrane glycoprotein 3 Proteins 0.000 description 4
- 102000036770 Islet Amyloid Polypeptide Human genes 0.000 description 4
- 108010041872 Islet Amyloid Polypeptide Proteins 0.000 description 4
- 102100038213 Lysosome-associated membrane glycoprotein 3 Human genes 0.000 description 4
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 4
- 108010076181 Proinsulin Proteins 0.000 description 4
- 238000000692 Student's t-test Methods 0.000 description 4
- 229960003942 amphotericin b Drugs 0.000 description 4
- 239000000427 antigen Substances 0.000 description 4
- 108091007433 antigens Proteins 0.000 description 4
- 102000036639 antigens Human genes 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 210000004271 bone marrow stromal cell Anatomy 0.000 description 4
- 238000004422 calculation algorithm Methods 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- JUFFVKRROAPVBI-PVOYSMBESA-N chembl1210015 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)N[C@H]1[C@@H]([C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@]3(O[C@@H](C[C@H](O)[C@H](O)CO)[C@H](NC(C)=O)[C@@H](O)C3)C(O)=O)O2)O)[C@@H](CO)O1)NC(C)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 JUFFVKRROAPVBI-PVOYSMBESA-N 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 238000013270 controlled release Methods 0.000 description 4
- 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 4
- 239000006185 dispersion Substances 0.000 description 4
- 230000008030 elimination Effects 0.000 description 4
- 238000003379 elimination reaction Methods 0.000 description 4
- 210000003890 endocrine cell Anatomy 0.000 description 4
- 230000007705 epithelial mesenchymal transition Effects 0.000 description 4
- 210000003527 eukaryotic cell Anatomy 0.000 description 4
- 229960001519 exenatide Drugs 0.000 description 4
- 238000000684 flow cytometry Methods 0.000 description 4
- 230000004927 fusion Effects 0.000 description 4
- 102000037865 fusion proteins Human genes 0.000 description 4
- 108020001507 fusion proteins Proteins 0.000 description 4
- 238000001476 gene delivery Methods 0.000 description 4
- 238000009396 hybridization Methods 0.000 description 4
- 238000003125 immunofluorescent labeling Methods 0.000 description 4
- 230000001771 impaired effect Effects 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 150000002632 lipids Chemical class 0.000 description 4
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 238000012544 monitoring process Methods 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 201000002528 pancreatic cancer Diseases 0.000 description 4
- 208000008443 pancreatic carcinoma Diseases 0.000 description 4
- 230000009996 pancreatic endocrine effect Effects 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- 210000001236 prokaryotic cell Anatomy 0.000 description 4
- 230000010076 replication Effects 0.000 description 4
- 230000001177 retroviral effect Effects 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 230000002123 temporal effect Effects 0.000 description 4
- 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 3
- 108020005544 Antisense RNA Proteins 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 102100030074 Dickkopf-related protein 1 Human genes 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 102100027043 Discoidin, CUB and LCCL domain-containing protein 2 Human genes 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 108700014808 Homeobox Protein Nkx-2.2 Proteins 0.000 description 3
- 102100028096 Homeobox protein Nkx-6.2 Human genes 0.000 description 3
- 108010077223 Homer Scaffolding Proteins Proteins 0.000 description 3
- 102000010029 Homer Scaffolding Proteins Human genes 0.000 description 3
- 101000864646 Homo sapiens Dickkopf-related protein 1 Proteins 0.000 description 3
- 101000911787 Homo sapiens Discoidin, CUB and LCCL domain-containing protein 2 Proteins 0.000 description 3
- 101000578258 Homo sapiens Homeobox protein Nkx-6.2 Proteins 0.000 description 3
- 101000603702 Homo sapiens Neurogenin-3 Proteins 0.000 description 3
- 241000713666 Lentivirus Species 0.000 description 3
- 108060001084 Luciferase Proteins 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 206010028813 Nausea Diseases 0.000 description 3
- 208000012902 Nervous system disease Diseases 0.000 description 3
- 108050000588 Neurogenic differentiation factor 1 Proteins 0.000 description 3
- 102100032063 Neurogenic differentiation factor 1 Human genes 0.000 description 3
- 102100038553 Neurogenin-3 Human genes 0.000 description 3
- 208000025966 Neurological disease Diseases 0.000 description 3
- 102000007354 PAX6 Transcription Factor Human genes 0.000 description 3
- 102100026450 POU domain, class 3, transcription factor 4 Human genes 0.000 description 3
- 101710133389 POU domain, class 3, transcription factor 4 Proteins 0.000 description 3
- 229930182555 Penicillin Natural products 0.000 description 3
- 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 3
- 108090000545 Proprotein Convertase 2 Proteins 0.000 description 3
- 108090000544 Proprotein convertase 1 Proteins 0.000 description 3
- 102000004085 Proprotein convertase 1 Human genes 0.000 description 3
- 238000011529 RT qPCR Methods 0.000 description 3
- 108700008625 Reporter Genes Proteins 0.000 description 3
- 108010017324 STAT3 Transcription Factor Proteins 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- 102100024040 Signal transducer and activator of transcription 3 Human genes 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000001464 adherent effect Effects 0.000 description 3
- 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 3
- 230000003321 amplification Effects 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 239000003184 complementary RNA Substances 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 238000005138 cryopreservation Methods 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000002612 dispersion medium Substances 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000002124 endocrine Effects 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 208000004104 gestational diabetes Diseases 0.000 description 3
- 230000003394 haemopoietic effect Effects 0.000 description 3
- 238000003018 immunoassay Methods 0.000 description 3
- 238000010166 immunofluorescence Methods 0.000 description 3
- 230000002458 infectious effect Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 238000007914 intraventricular administration Methods 0.000 description 3
- 238000011031 large-scale manufacturing process Methods 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 238000001638 lipofection Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000012317 liver biopsy Methods 0.000 description 3
- 238000002493 microarray Methods 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 230000008693 nausea Effects 0.000 description 3
- 230000004770 neurodegeneration Effects 0.000 description 3
- 208000015122 neurodegenerative disease Diseases 0.000 description 3
- 238000003199 nucleic acid amplification method Methods 0.000 description 3
- 210000004940 nucleus Anatomy 0.000 description 3
- 230000005305 organ development Effects 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 229940049954 penicillin Drugs 0.000 description 3
- 102000040430 polynucleotide Human genes 0.000 description 3
- 108091033319 polynucleotide Proteins 0.000 description 3
- 239000002157 polynucleotide Substances 0.000 description 3
- 210000003240 portal vein Anatomy 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 230000001737 promoting effect Effects 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 238000007619 statistical method Methods 0.000 description 3
- 229960005322 streptomycin Drugs 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- ANRHNWWPFJCPAZ-UHFFFAOYSA-M thionine Chemical compound [Cl-].C1=CC(N)=CC2=[S+]C3=CC(N)=CC=C3N=C21 ANRHNWWPFJCPAZ-UHFFFAOYSA-M 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- 230000010474 transient expression Effects 0.000 description 3
- 241000701447 unidentified baculovirus Species 0.000 description 3
- 230000004580 weight loss Effects 0.000 description 3
- 208000016261 weight loss Diseases 0.000 description 3
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000035404 Autolysis Diseases 0.000 description 2
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 2
- 108010027344 Basic Helix-Loop-Helix Transcription Factors Proteins 0.000 description 2
- 102000018720 Basic Helix-Loop-Helix Transcription Factors Human genes 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 108010001857 Cell Surface Receptors Proteins 0.000 description 2
- 102000000844 Cell Surface Receptors Human genes 0.000 description 2
- 206010057248 Cell death Diseases 0.000 description 2
- 208000000668 Chronic Pancreatitis Diseases 0.000 description 2
- 102000029816 Collagenase Human genes 0.000 description 2
- 108060005980 Collagenase Proteins 0.000 description 2
- 241000701022 Cytomegalovirus Species 0.000 description 2
- 101100518002 Danio rerio nkx2.2a gene Proteins 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 102100037362 Fibronectin Human genes 0.000 description 2
- 108010067306 Fibronectins Proteins 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 102000001267 GSK3 Human genes 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 description 2
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 2
- 102100031470 Homeobox protein ARX Human genes 0.000 description 2
- 102100027886 Homeobox protein Nkx-2.2 Human genes 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 2
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 2
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 2
- 101100460496 Homo sapiens NKX2-2 gene Proteins 0.000 description 2
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 2
- 101000639146 Homo sapiens Vesicle-associated membrane protein 4 Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 102100022338 Integrin alpha-M Human genes 0.000 description 2
- 206010023126 Jaundice Diseases 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- 101100516510 Mus musculus Neurog3 gene Proteins 0.000 description 2
- 108010032788 PAX6 Transcription Factor Proteins 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 206010033649 Pancreatitis chronic Diseases 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 102000006437 Proprotein Convertases Human genes 0.000 description 2
- 108010044159 Proprotein Convertases Proteins 0.000 description 2
- 208000003251 Pruritus Diseases 0.000 description 2
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 2
- 108010016283 TCF Transcription Factors Proteins 0.000 description 2
- 102000000479 TCF Transcription Factors Human genes 0.000 description 2
- 206010043458 Thirst Diseases 0.000 description 2
- 102100031489 Vesicle-associated membrane protein 4 Human genes 0.000 description 2
- 206010047513 Vision blurred Diseases 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- 230000003187 abdominal effect Effects 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 208000009956 adenocarcinoma Diseases 0.000 description 2
- 210000004504 adult stem cell Anatomy 0.000 description 2
- 230000003698 anagen phase Effects 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 239000003429 antifungal agent Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 230000002238 attenuated effect Effects 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- WQZGKKKJIJFFOK-FPRJBGLDSA-N beta-D-galactose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-FPRJBGLDSA-N 0.000 description 2
- 108010005774 beta-Galactosidase Proteins 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 210000004413 cardiac myocyte Anatomy 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 230000011748 cell maturation Effects 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 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
- 238000011260 co-administration Methods 0.000 description 2
- 230000004186 co-expression Effects 0.000 description 2
- 230000008045 co-localization Effects 0.000 description 2
- 229960002424 collagenase Drugs 0.000 description 2
- 230000009260 cross reactivity Effects 0.000 description 2
- 230000002354 daily effect Effects 0.000 description 2
- 230000003412 degenerative effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 238000005538 encapsulation Methods 0.000 description 2
- 206010016256 fatigue Diseases 0.000 description 2
- 235000019197 fats Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 230000004190 glucose uptake Effects 0.000 description 2
- 229930195712 glutamate Natural products 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 230000005484 gravity Effects 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000003054 hormonal effect Effects 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 238000010185 immunofluorescence analysis Methods 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 239000007951 isotonicity adjuster Substances 0.000 description 2
- 230000007803 itching Effects 0.000 description 2
- 210000002510 keratinocyte Anatomy 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 239000003094 microcapsule Substances 0.000 description 2
- 230000027939 micturition Effects 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 210000001178 neural stem cell Anatomy 0.000 description 2
- 210000004498 neuroglial cell Anatomy 0.000 description 2
- 230000000926 neurological effect Effects 0.000 description 2
- 229960003966 nicotinamide Drugs 0.000 description 2
- 235000005152 nicotinamide Nutrition 0.000 description 2
- 239000011570 nicotinamide Substances 0.000 description 2
- 239000000346 nonvolatile oil Substances 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 210000000277 pancreatic duct Anatomy 0.000 description 2
- 230000002085 persistent effect Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 230000001902 propagating effect Effects 0.000 description 2
- 238000002731 protein assay Methods 0.000 description 2
- 230000022558 protein metabolic process Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000000275 quality assurance Methods 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 238000003753 real-time PCR Methods 0.000 description 2
- 230000010837 receptor-mediated endocytosis Effects 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 230000028043 self proteolysis Effects 0.000 description 2
- 210000002325 somatostatin-secreting cell Anatomy 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000010257 thawing Methods 0.000 description 2
- 230000001131 transforming effect Effects 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 230000008673 vomiting Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- 210000005253 yeast cell Anatomy 0.000 description 2
- OZFAFGSSMRRTDW-UHFFFAOYSA-N (2,4-dichlorophenyl) benzenesulfonate Chemical compound ClC1=CC(Cl)=CC=C1OS(=O)(=O)C1=CC=CC=C1 OZFAFGSSMRRTDW-UHFFFAOYSA-N 0.000 description 1
- ASWBNKHCZGQVJV-UHFFFAOYSA-N (3-hexadecanoyloxy-2-hydroxypropyl) 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(O)COP([O-])(=O)OCC[N+](C)(C)C ASWBNKHCZGQVJV-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- 101150090724 3 gene Proteins 0.000 description 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 206010000087 Abdominal pain upper Diseases 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 206010001258 Adenoviral infections Diseases 0.000 description 1
- 208000010370 Adenoviridae Infections Diseases 0.000 description 1
- 206010060931 Adenovirus infection Diseases 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 206010003402 Arthropod sting Diseases 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 239000002028 Biomass Substances 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 240000001432 Calendula officinalis Species 0.000 description 1
- 235000005881 Calendula officinalis Nutrition 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 102000005403 Casein Kinases Human genes 0.000 description 1
- 108010031425 Casein Kinases Proteins 0.000 description 1
- 108010076667 Caspases Proteins 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 108010051219 Cre recombinase Proteins 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- MNQZXJOMYWMBOU-VKHMYHEASA-N D-glyceraldehyde Chemical compound OC[C@@H](O)C=O MNQZXJOMYWMBOU-VKHMYHEASA-N 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 102000052510 DNA-Binding Proteins Human genes 0.000 description 1
- 108700020911 DNA-Binding Proteins Proteins 0.000 description 1
- 241000252212 Danio rerio Species 0.000 description 1
- 101000923091 Danio rerio Aristaless-related homeobox protein Proteins 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 1
- 239000012983 Dulbecco’s minimal essential medium Substances 0.000 description 1
- 108091035710 E-box Proteins 0.000 description 1
- 108010013369 Enteropeptidase Proteins 0.000 description 1
- 102100029727 Enteropeptidase Human genes 0.000 description 1
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 108010074860 Factor Xa Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 201000008808 Fibrosarcoma Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 108010045438 Frizzled receptors Proteins 0.000 description 1
- 102000005698 Frizzled receptors Human genes 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 108090001126 Furin Proteins 0.000 description 1
- 102000027587 GPCRs class F Human genes 0.000 description 1
- 108091008884 GPCRs class F Proteins 0.000 description 1
- 101100180045 Gallus gallus ISL1 gene Proteins 0.000 description 1
- 102400000921 Gastrin Human genes 0.000 description 1
- 108010052343 Gastrins Proteins 0.000 description 1
- 206010018404 Glucagonoma Diseases 0.000 description 1
- 206010018429 Glucose tolerance impaired Diseases 0.000 description 1
- 241000288105 Grus Species 0.000 description 1
- 102000006354 HLA-DR Antigens Human genes 0.000 description 1
- 108010058597 HLA-DR Antigens Proteins 0.000 description 1
- 241000034673 Holographis Species 0.000 description 1
- 101000935043 Homo sapiens Integrin beta-1 Proteins 0.000 description 1
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 1
- 101100518189 Homo sapiens PDHX gene Proteins 0.000 description 1
- 101100519290 Homo sapiens PDX1 gene Proteins 0.000 description 1
- 101000632994 Homo sapiens Somatostatin Proteins 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 241000701109 Human adenovirus 2 Species 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102100025304 Integrin beta-1 Human genes 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
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 108010015167 Low Density Lipoprotein Receptor-Related Protein-5 Proteins 0.000 description 1
- 102100021926 Low-density lipoprotein receptor-related protein 5 Human genes 0.000 description 1
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 108700011259 MicroRNAs Proteins 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 102000008763 Neurofilament Proteins Human genes 0.000 description 1
- 108010088373 Neurofilament Proteins Proteins 0.000 description 1
- 101710096141 Neurogenin-3 Proteins 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 108091005461 Nucleic proteins Chemical group 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 101150081664 PAX6 gene Proteins 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 206010033627 Pancreatic injury Diseases 0.000 description 1
- 206010033635 Pancreatic pseudocyst Diseases 0.000 description 1
- 206010033647 Pancreatitis acute Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 229920002685 Polyoxyl 35CastorOil Polymers 0.000 description 1
- 241001417524 Pomacanthidae Species 0.000 description 1
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 1
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 1
- 102000006478 Protein Phosphatase 2 Human genes 0.000 description 1
- 108010058956 Protein Phosphatase 2 Proteins 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 102000012083 SOX9 Transcription Factor Human genes 0.000 description 1
- 108010036426 SOX9 Transcription Factor Proteins 0.000 description 1
- 102000001712 STAT5 Transcription Factor Human genes 0.000 description 1
- 108010029477 STAT5 Transcription Factor Proteins 0.000 description 1
- 208000006504 Scorpion Stings Diseases 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 108010048349 Steroidogenic Factor 1 Proteins 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 206010042674 Swelling Diseases 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 1
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 102000014104 Transcription factor MafA Human genes 0.000 description 1
- 108050003977 Transcription factor MafA Proteins 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 102000004338 Transferrin Human genes 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 239000012840 University of Wisconsin (UW) solution Substances 0.000 description 1
- 239000005862 Whey Substances 0.000 description 1
- 102000007544 Whey Proteins Human genes 0.000 description 1
- 108010046377 Whey Proteins Proteins 0.000 description 1
- 102000044880 Wnt3A Human genes 0.000 description 1
- 108700013515 Wnt3A Proteins 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 description 1
- 208000020560 abdominal swelling Diseases 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 208000006336 acinar cell carcinoma Diseases 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 201000003229 acute pancreatitis Diseases 0.000 description 1
- 208000011589 adenoviridae infectious disease Diseases 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 206010001584 alcohol abuse Diseases 0.000 description 1
- 208000025746 alcohol use disease Diseases 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 102000013529 alpha-Fetoproteins Human genes 0.000 description 1
- 108010026331 alpha-Fetoproteins Proteins 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 230000006470 autoimmune attack Effects 0.000 description 1
- 239000013602 bacteriophage vector Substances 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- OGBUMNBNEWYMNJ-UHFFFAOYSA-N batilol Chemical class CCCCCCCCCCCCCCCCCCOCC(O)CO OGBUMNBNEWYMNJ-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 239000003613 bile acid Substances 0.000 description 1
- 239000003833 bile salt Substances 0.000 description 1
- 229940093761 bile salts Drugs 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000014461 bone development Effects 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- AOXOCDRNSPFDPE-UKEONUMOSA-N chembl413654 Chemical compound C([C@H](C(=O)NCC(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](C)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@@H](N)CCC(O)=O)C1=CC=C(O)C=C1 AOXOCDRNSPFDPE-UKEONUMOSA-N 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 238000013189 cholangiography Methods 0.000 description 1
- 201000001883 cholelithiasis Diseases 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 210000001612 chondrocyte Anatomy 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 235000019504 cigarettes Nutrition 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000002591 computed tomography Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 208000002445 cystadenocarcinoma Diseases 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 108700041286 delta Proteins 0.000 description 1
- 230000000368 destabilizing effect Effects 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 230000002542 deteriorative effect Effects 0.000 description 1
- 229960002086 dextran Drugs 0.000 description 1
- 229960000633 dextran sulfate Drugs 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 229940079919 digestives enzyme preparation Drugs 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000002183 duodenal effect Effects 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 101150097231 eg gene Proteins 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 238000007459 endoscopic retrograde cholangiopancreatography Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 230000008995 epigenetic change Effects 0.000 description 1
- 210000003999 epithelial cell of bile duct Anatomy 0.000 description 1
- 210000004955 epithelial membrane Anatomy 0.000 description 1
- 235000020774 essential nutrients Nutrition 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 210000003754 fetus Anatomy 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 108010021843 fluorescent protein 583 Proteins 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 235000021588 free fatty acids Nutrition 0.000 description 1
- IECPWNUMDGFDKC-MZJAQBGESA-N fusidic acid Chemical class O[C@@H]([C@@H]12)C[C@H]3\C(=C(/CCC=C(C)C)C(O)=O)[C@@H](OC(C)=O)C[C@]3(C)[C@@]2(C)CC[C@@H]2[C@]1(C)CC[C@@H](O)[C@H]2C IECPWNUMDGFDKC-MZJAQBGESA-N 0.000 description 1
- 208000001130 gallstones Diseases 0.000 description 1
- 208000015419 gastrin-producing neuroendocrine tumor Diseases 0.000 description 1
- 201000000052 gastrinoma Diseases 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 238000012252 genetic analysis Methods 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 239000008241 heterogeneous mixture Substances 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 102000052072 human NEUROG3 Human genes 0.000 description 1
- 102000045305 human SST Human genes 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 238000002991 immunohistochemical analysis Methods 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 210000004263 induced pluripotent stem cell Anatomy 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000013383 initial experiment Methods 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 239000013546 insoluble monolayer Substances 0.000 description 1
- 206010022498 insulinoma Diseases 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 238000005184 irreversible process Methods 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 208000012866 low blood pressure Diseases 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 201000001240 maturity-onset diabetes of the young type 9 Diseases 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- STZCRXQWRGQSJD-GEEYTBSJSA-M methyl orange Chemical compound [Na+].C1=CC(N(C)C)=CC=C1\N=N\C1=CC=C(S([O-])(=O)=O)C=C1 STZCRXQWRGQSJD-GEEYTBSJSA-M 0.000 description 1
- 229940012189 methyl orange Drugs 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 239000002679 microRNA Substances 0.000 description 1
- 238000010208 microarray analysis Methods 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 239000011785 micronutrient Substances 0.000 description 1
- 235000013369 micronutrients Nutrition 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000002200 mouth mucosa Anatomy 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 229940051866 mouthwash Drugs 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 108010050062 mutacin GS-5 Proteins 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 239000006218 nasal suppository Substances 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000003061 neural cell Anatomy 0.000 description 1
- 210000005044 neurofilament Anatomy 0.000 description 1
- 230000003955 neuronal function Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 230000008779 noncanonical pathway Effects 0.000 description 1
- 238000012758 nuclear staining Methods 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 description 1
- 230000015031 pancreas development Effects 0.000 description 1
- 108700011804 pancreatic and duodenal homeobox 1 Proteins 0.000 description 1
- 208000021255 pancreatic insulinoma Diseases 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 229960003742 phenol Drugs 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
- 150000003904 phospholipids Chemical class 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000003169 placental effect Effects 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 210000001778 pluripotent stem cell Anatomy 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 235000015277 pork Nutrition 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000003334 potential effect Effects 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000003762 quantitative reverse transcription PCR Methods 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 230000010656 regulation of insulin secretion Effects 0.000 description 1
- 230000001718 repressive effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229910052702 rhenium Inorganic materials 0.000 description 1
- WUAPFZMCVAUBPE-UHFFFAOYSA-N rhenium atom Chemical compound [Re] WUAPFZMCVAUBPE-UHFFFAOYSA-N 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 210000004739 secretory vesicle Anatomy 0.000 description 1
- 238000005204 segregation Methods 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 230000007781 signaling event Effects 0.000 description 1
- 230000022379 skeletal muscle tissue development Effects 0.000 description 1
- 230000012488 skeletal system development Effects 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000009331 sowing Methods 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000003153 stable transfection Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229960004906 thiomersal Drugs 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 108091006106 transcriptional activators Proteins 0.000 description 1
- 108091006108 transcriptional coactivators Proteins 0.000 description 1
- 238000003151 transfection method Methods 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- 230000009495 transient activation Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 229940038773 trisodium citrate Drugs 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
- 238000010798 ubiquitination Methods 0.000 description 1
- 230000034512 ubiquitination Effects 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000009777 vacuum freeze-drying Methods 0.000 description 1
- ATCJTYORYKLVIA-SRXJVYAUSA-N vamp regimen Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1.C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1.C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C(C45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C=O)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 ATCJTYORYKLVIA-SRXJVYAUSA-N 0.000 description 1
- 239000002435 venom Substances 0.000 description 1
- 210000001048 venom Anatomy 0.000 description 1
- 231100000611 venom Toxicity 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 238000002689 xenotransplantation Methods 0.000 description 1
- 238000013316 zoning Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- 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
- A61K35/39—Pancreas; Islets of Langerhans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
-
- 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
- C07K14/575—Hormones
- C07K14/62—Insulins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/42—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins
-
- 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
-
- 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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
-
- 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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
-
- 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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
- C12N15/861—Adenoviral vectors
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0676—Pancreatic cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/60—Transcription factors
-
- 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
- C12N2506/00—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells
- C12N2506/14—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from hepatocytes
-
- 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
- C12N2510/00—Genetically modified cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/10011—Adenoviridae
- C12N2710/10311—Mastadenovirus, e.g. human or simian adenoviruses
- C12N2710/10341—Use of virus, viral particle or viral elements as a vector
- C12N2710/10343—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- General Health & Medical Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Microbiology (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Cell Biology (AREA)
- Diabetes (AREA)
- Virology (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Endocrinology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Developmental Biology & Embryology (AREA)
- Physiology (AREA)
- Nutrition Science (AREA)
- Toxicology (AREA)
- Emergency Medicine (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462098050P | 2014-12-30 | 2014-12-30 | |
| PCT/IL2015/051267 WO2016108237A1 (en) | 2014-12-30 | 2015-12-30 | Methods of transdifferentiation and methods of use thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201791508A1 EA201791508A1 (ru) | 2018-05-31 |
| EA035360B1 true EA035360B1 (ru) | 2020-06-02 |
Family
ID=56284403
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201791508A EA035360B1 (ru) | 2014-12-30 | 2015-12-30 | Способы трансдифференцировки и способы их использования |
Country Status (15)
| Country | Link |
|---|---|
| US (3) | US10179151B2 (enExample) |
| EP (2) | EP3240576B1 (enExample) |
| JP (1) | JP6817943B2 (enExample) |
| KR (1) | KR102487883B1 (enExample) |
| CN (1) | CN107750170B (enExample) |
| AU (1) | AU2015373129B2 (enExample) |
| BR (1) | BR112017014280A2 (enExample) |
| CA (1) | CA2972569A1 (enExample) |
| CO (1) | CO2017006937A2 (enExample) |
| EA (1) | EA035360B1 (enExample) |
| IL (1) | IL253234B (enExample) |
| MA (1) | MA41296A (enExample) |
| MX (1) | MX378321B (enExample) |
| SG (1) | SG11201705344VA (enExample) |
| WO (1) | WO2016108237A1 (enExample) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SG11201510209SA (en) | 2013-06-13 | 2016-01-28 | Orgenesis Ltd | Cell populations, methods of transdifferention and methods of use thereof |
| US10231817B2 (en) | 2013-09-24 | 2019-03-19 | Giner Life Sciences, Inc. | System for gas treatment of a cell implant |
| MA41296A (fr) | 2014-12-30 | 2017-11-07 | Orgenesis Ltd | Procédés de transdifférenciation et procédés d'utilisation de ceux-ci |
| WO2017192717A1 (en) | 2016-05-05 | 2017-11-09 | Southwest Research Institute | Three-dimensional bioreactor for cell expansion and related applications |
| US11033666B2 (en) | 2016-11-15 | 2021-06-15 | Giner Life Sciences, Inc. | Percutaneous gas diffusion device suitable for use with a subcutaneous implant |
| WO2018204867A1 (en) | 2017-05-04 | 2018-11-08 | Giner, Inc. | Robust, implantable gas delivery device and methods, systems and devices including same |
| EP3635106A4 (en) | 2017-05-08 | 2021-01-06 | Orgenesis Ltd. | POPULATIONS OF TRANSDIFFERENTIATED CELLS AND THEIR METHODS OF USE |
| WO2018220623A1 (en) * | 2017-05-29 | 2018-12-06 | Orgenesis Ltd. | Compositions and methods for providing cell replacement therapy |
| JP2020537522A (ja) | 2017-10-13 | 2020-12-24 | イーエムベーアー−インスティテュート フュール モレクラレ バイオテクノロジー ゲゼルシャフト ミット ベシュレンクテル ハフツング | 体細胞の増強された再プログラミング |
| WO2019171377A1 (en) * | 2018-03-06 | 2019-09-12 | Orgenesis Inc | Three dimensional clusters of transdifferentiated cells, compositions and methods thereof |
| US11149244B2 (en) | 2018-04-04 | 2021-10-19 | Southwest Research Institute | Three-dimensional bioreactor for T-cell activation and expansion for immunotherapy |
| WO2020068840A1 (en) | 2018-09-24 | 2020-04-02 | Southwest Research Institute | Three-dimensional bioreactors |
| EP3816276A1 (en) * | 2019-10-31 | 2021-05-05 | Unicyte Islet AG | Viable pancreatic islet-like cell structures and a method of preparing thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004098646A1 (en) * | 2003-05-12 | 2004-11-18 | Sarah Ferber | Methods of inducing regulated pancreatic hormone production in non-pancreatic islet tissues |
| WO2009126927A2 (en) * | 2008-04-11 | 2009-10-15 | Joslin Diabetes Center, Inc. | Methods of generating insulin-producing cells |
| WO2010022395A2 (en) * | 2008-08-22 | 2010-02-25 | President And Fellows Of Harvard College | Methods of reprogramming cells |
Family Cites Families (68)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
| US4980286A (en) | 1985-07-05 | 1990-12-25 | Whitehead Institute For Biomedical Research | In vivo introduction and expression of foreign genetic material in epithelial cells |
| US4737323A (en) | 1986-02-13 | 1988-04-12 | Liposome Technology, Inc. | Liposome extrusion method |
| JP2874751B2 (ja) | 1986-04-09 | 1999-03-24 | ジェンザイム・コーポレーション | 希望する蛋白質をミルク中へ分泌する遺伝子移植動物 |
| US4837028A (en) | 1986-12-24 | 1989-06-06 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| US4873316A (en) | 1987-06-23 | 1989-10-10 | Biogen, Inc. | Isolation of exogenous recombinant proteins from the milk of transgenic mammals |
| US4992417A (en) | 1987-07-17 | 1991-02-12 | Mount Sinai School Of Medicine | Superactive human insulin analogues |
| US5082670A (en) | 1988-12-15 | 1992-01-21 | The Regents Of The University Of California | Method of grafting genetically modified cells to treat defects, disease or damage or the central nervous system |
| US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
| US5328470A (en) | 1989-03-31 | 1994-07-12 | The Regents Of The University Of Michigan | Treatment of diseases by site-specific instillation of cells or site-specific transformation of cells and kits therefor |
| US5427940A (en) | 1991-06-03 | 1995-06-27 | Board Of Regents, The University Of Texas System | Engineered cells producing insulin in response to glucose |
| CA2146747C (en) | 1992-10-09 | 2006-12-19 | Brian A. Naughton | Liver reserve cells |
| US5523226A (en) | 1993-05-14 | 1996-06-04 | Biotechnology Research And Development Corp. | Transgenic swine compositions and methods |
| US5424286A (en) | 1993-05-24 | 1995-06-13 | Eng; John | Exendin-3 and exendin-4 polypeptides, and pharmaceutical compositions comprising same |
| DE69435026D1 (de) | 1993-08-16 | 2007-10-31 | Res Dev Foundation | Ein homeobox-faktor der insulin-expression in pankreatischen inselnzellen stimuliert |
| US5858973A (en) | 1994-02-23 | 1999-01-12 | The General Hospital Corporation | Transcription factor and uses therefor |
| IL114193A (en) | 1994-06-20 | 2000-02-29 | Teva Pharma | Ophthalmic pharmaceutical compositions based on sodium alginate |
| US5849989A (en) | 1994-10-07 | 1998-12-15 | Ontogeny, Inc. | Insulin promoter factor, and uses related thereto |
| JP2000501290A (ja) | 1995-11-30 | 2000-02-08 | リサーチ ディベロップメント ファンデーション | ソマトスタチン及びインシュリン生成を刺激する化合物のスクリーニング・アッセイ |
| IL118376A0 (en) | 1996-05-22 | 1996-09-12 | Univ Ben Gurion | Polysaccharide sponges for cell culture and transplantation |
| JP2000513227A (ja) | 1996-06-24 | 2000-10-10 | ビーボウアールエックス ファーマスーティカルズ,インコーポレイテッド | インスリン分泌細胞の単離および増殖方法 |
| US6114113A (en) | 1997-08-11 | 2000-09-05 | Chiron Corporation | High efficiency genetic modification method |
| CA2221195A1 (en) | 1997-11-14 | 1999-05-14 | Chantal E. Holy | Biodegradable polymer matrix |
| US6143293A (en) | 1998-03-26 | 2000-11-07 | Carnegie Mellon | Assembled scaffolds for three dimensional cell culturing and tissue generation |
| IL124957A0 (en) | 1998-06-16 | 1999-01-26 | Univ Ben Gurion | Active ingredient delivery systems and devices based on porous matrices |
| US6242666B1 (en) | 1998-12-16 | 2001-06-05 | The Scripps Research Institute | Animal model for identifying a common stem/progenitor to liver cells and pancreatic cells |
| US8778899B2 (en) | 1999-06-01 | 2014-07-15 | Sarah Ferber | Methods of inducing regulated pancreatic hormone production in non-pancreatic islet tissues |
| US6774120B1 (en) | 1999-06-01 | 2004-08-10 | Sarah Ferber | Methods of inducing regulated pancreatic hormone production in non-pancreatic islet tissues |
| US6716824B1 (en) | 1999-10-22 | 2004-04-06 | F. Charles Brunicardi | Treatment of pancreatic adenocarcinoma by cytotoxic gene therapy |
| US6759039B2 (en) | 2000-06-30 | 2004-07-06 | Amcyte, Inc. | Culturing pancreatic stem cells having a specified, intermediate stage of development |
| US7214371B1 (en) | 2000-09-01 | 2007-05-08 | Ben-Gurion University Of The Negev Research & Development Authority | Tissue engineered biografts for repair of damaged myocardium |
| US7524492B2 (en) | 2001-08-31 | 2009-04-28 | Joslin Diabetes Center, Inc. | Insulin related transcription factor and uses thereof |
| US20050053588A1 (en) | 2001-10-18 | 2005-03-10 | Li Yin | Conversion of liver stem and progenitor cells to pancreatic functional cells |
| US7722894B2 (en) | 2001-10-22 | 2010-05-25 | Massachusetts Institute Of Technology | Biodegradable polymer |
| GB2399823B (en) | 2001-12-07 | 2006-02-15 | Geron Corp | Islet cells from primate pluripotent stem cells |
| WO2003072728A2 (en) * | 2002-02-22 | 2003-09-04 | University Of Florida | Cellular trans-differentiation |
| GB0206357D0 (en) | 2002-03-18 | 2002-05-01 | Univ Bath | Cells |
| JP4136434B2 (ja) | 2002-04-17 | 2008-08-20 | 進 清野 | インスリン産生細胞の誘導 |
| CN1662643A (zh) | 2002-05-28 | 2005-08-31 | 贝克顿·迪金森公司 | 人腺泡细胞的扩增和转分化 |
| MXPA05011896A (es) | 2003-05-05 | 2006-05-25 | Univ Ben Gurion | Preparaciones polimericas reticuladas inyectables y sus usos. |
| WO2005005607A2 (en) | 2003-06-30 | 2005-01-20 | Lifescan, Inc. | Seeding pancreatic cells on porous matrices |
| AU2004269395A1 (en) | 2003-08-27 | 2005-03-10 | Stemcells California, Inc. | Enriched pancreatic stem cell and progenitor cell populations, and methods for identifying, isolating and enriching for these populations |
| WO2005056747A2 (en) | 2003-12-09 | 2005-06-23 | Ben-Gurion University Of The Negev Research And Development Authority | Pulse-medium perfusion bioreactor with improved mass transport for multiple 3-d cell constructs |
| EP1784481A1 (en) | 2004-08-25 | 2007-05-16 | Technion Research And Development Foundation, Ltd. | Methods of generating embryoid bodies using three dimensional scaffolds |
| US8679484B2 (en) | 2005-03-02 | 2014-03-25 | Polyrizon Ltd. | Method for removal of toxins from mucosal membranes |
| US9216236B2 (en) | 2005-03-07 | 2015-12-22 | Technion Research & Development Foundation Limited | Natural tissue-derived decellularized matrix and methods of generating and using same |
| US7517856B2 (en) | 2005-10-11 | 2009-04-14 | Ben-Gurion University Of The Negev Research And Development Authority | Bioconjugates comprising sulfated polysaccharides and their uses |
| US20100137202A1 (en) * | 2006-07-19 | 2010-06-03 | University Of Florida Research Foundation | Compositions for reprogramming a cell and uses therefor |
| AU2007335753B2 (en) | 2006-12-18 | 2013-12-05 | Ben Gurion University Of The Negev | Scaffolding for tissue regeneration or repair |
| US20100226976A1 (en) | 2007-07-11 | 2010-09-09 | Marcelle Machluf | Encapsulated mesenchymal stem cells and uses thereof |
| IL187707A0 (en) | 2007-11-27 | 2008-11-03 | Univ Ben Gurion | Alginate scaffold in hepatectomy |
| JP5717253B2 (ja) | 2009-08-02 | 2015-05-13 | 学校法人東京女子医科大学 | 膵島細胞シート、製造方法及びその利用方法 |
| AU2010312240B2 (en) * | 2009-10-31 | 2016-12-15 | Genesis Technologies Limited | Methods for reprogramming cells and uses thereof |
| JP2011223993A (ja) | 2010-03-30 | 2011-11-10 | Kumamoto Univ | 幹細胞の分化誘導方法 |
| EP3399026B1 (en) | 2010-06-14 | 2024-06-26 | The Scripps Research Institute | Reprogramming of cells to a new fate |
| EP2741753A2 (en) | 2011-08-09 | 2014-06-18 | Yeda Research and Development Co. Ltd. | Downregulation of mir-7 for promotion of beta cell differentiation and insulin production |
| WO2013124855A1 (en) | 2012-02-21 | 2013-08-29 | Ben-Gurion University Of The Negev Research And Development Authority | Hydrogel system comprising spatially separated bioactive polypeptides |
| WO2014102801A1 (en) | 2012-12-30 | 2014-07-03 | Hadasit Medical Research Services And Development Ltd. | Use of alginate compositions in preventing or reducing liver damage caused by a hepatotoxic agent |
| KR102757386B1 (ko) | 2013-05-08 | 2025-01-21 | 인리젠 | 단리된 신장 세포를 포함하는 오가노이드 및 이의 용도 |
| SG11201510209SA (en) * | 2013-06-13 | 2016-01-28 | Orgenesis Ltd | Cell populations, methods of transdifferention and methods of use thereof |
| EP3107549B1 (en) | 2014-02-20 | 2020-07-01 | B.G. Negev Technologies and Applications Ltd. | Anionic polyplexes for use in the delivery of nucleic acids |
| CA2950132C (en) | 2014-05-30 | 2022-01-18 | The Secant Group, Llc | Water-mediated preparations of polymeric materials |
| WO2015186127A1 (en) | 2014-06-02 | 2015-12-10 | B. G. Negev Technologies And Applications Ltd | Site-selective modification of polysaccharides and applications thereof |
| MA41296A (fr) | 2014-12-30 | 2017-11-07 | Orgenesis Ltd | Procédés de transdifférenciation et procédés d'utilisation de ceux-ci |
| EP3400074B1 (en) | 2016-01-07 | 2021-10-20 | B.G. Negev Technologies and Applications Ltd., at Ben-Gurion University | Compositions for generating immunotolerant responses |
| US20170290954A1 (en) | 2016-04-07 | 2017-10-12 | B. G. Negev Technologies And Applications Ltd., At Ben-Gurion University | Compositions and methods for treating spinal cord injury |
| WO2017175229A1 (en) | 2016-04-07 | 2017-10-12 | B.G. Negev Technologies And Applications Ltd. | Polysaccharide compositions and uses thereof |
| EP3635106A4 (en) | 2017-05-08 | 2021-01-06 | Orgenesis Ltd. | POPULATIONS OF TRANSDIFFERENTIATED CELLS AND THEIR METHODS OF USE |
-
2015
- 2015-12-29 MA MA041296A patent/MA41296A/fr unknown
- 2015-12-30 KR KR1020177021293A patent/KR102487883B1/ko active Active
- 2015-12-30 EP EP15875374.9A patent/EP3240576B1/en active Active
- 2015-12-30 EP EP20156154.5A patent/EP3698803B1/en active Active
- 2015-12-30 SG SG11201705344VA patent/SG11201705344VA/en unknown
- 2015-12-30 MX MX2017008669A patent/MX378321B/es unknown
- 2015-12-30 WO PCT/IL2015/051267 patent/WO2016108237A1/en not_active Ceased
- 2015-12-30 US US14/983,657 patent/US10179151B2/en active Active
- 2015-12-30 CA CA2972569A patent/CA2972569A1/en active Pending
- 2015-12-30 JP JP2017535829A patent/JP6817943B2/ja not_active Expired - Fee Related
- 2015-12-30 AU AU2015373129A patent/AU2015373129B2/en not_active Ceased
- 2015-12-30 EA EA201791508A patent/EA035360B1/ru unknown
- 2015-12-30 BR BR112017014280-5A patent/BR112017014280A2/pt not_active Application Discontinuation
- 2015-12-30 CN CN201580077116.8A patent/CN107750170B/zh active Active
-
2017
- 2017-06-29 IL IL253234A patent/IL253234B/en active IP Right Grant
- 2017-07-11 CO CONC2017/0006937A patent/CO2017006937A2/es unknown
-
2018
- 2018-11-29 US US16/203,654 patent/US10668107B2/en not_active Expired - Fee Related
-
2020
- 2020-04-01 US US16/836,967 patent/US11617769B2/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004098646A1 (en) * | 2003-05-12 | 2004-11-18 | Sarah Ferber | Methods of inducing regulated pancreatic hormone production in non-pancreatic islet tissues |
| WO2009126927A2 (en) * | 2008-04-11 | 2009-10-15 | Joslin Diabetes Center, Inc. | Methods of generating insulin-producing cells |
| WO2010022395A2 (en) * | 2008-08-22 | 2010-02-25 | President And Fellows Of Harvard College | Methods of reprogramming cells |
Non-Patent Citations (7)
| Title |
|---|
| Berneman-Zeitouni, Dana, et al.: "The temporal and hierarchical control of transcription factors-induced liver to pancreas transdifferentiation." PloS one9.2 (04.02.2014): e87812. Retrieved from the internet on: 05.04.2016; URL: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.008781204, Feb 2014 (2014/02/04), whole document * |
| Ham, Dong-Sik, et al.: "Generation of insulin producing cells from the mouse primary hepatocytes." Tissue Eng Reg Med 8 (2011): 564-573. Retrieved from the internet on: 05.04.2016; URL: http://www.pnas.org/content/102/22/7964.full.pdf, 31 Dec 2011 (2011/12/31), whole document * |
| Meivar Levy, Irit et al.: "Pancreatic and duodenal homeobox gene I induces hepatic dedifferentiation by suppressing the expression of CCAAT/enhancer?binding protein?" Hepatology 46.3 (15.09.2007): 898-905. Retrieved from the Internet on: 11.04.2016; URL: https://www.researchgate.net/profile/Eli_Mor/publication/6135085_Pancreatic_and_duodenal_homeobox_gene_I_induces_hepatic_dedifferentiation_by_suppressing_the_expression_of_CCAATenhancer-binding_protein_/links/556cbc6c08aec226830547a2.pdf, 15 Sep 2007 (2007/09/15), Fig. 3 * |
| Meivar-Levy, Irit et al.: "Human liver cells expressing albumin and mesenchymal characteristics give rise to insulin-producing cells." Journal of transplantation 2011 (24.08.2011). Retrieved from the Internet on: 12.04.2016; URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3163017/, 24 Aug 2011 (2011/08/24), whole document, page 10 left hand col. 2nd para. * |
| Sapir, Tamar et al.: "Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells." Proceedings of the National Academy of Sciences 102.22 (31.05.2005): 7964-7969. Retrieved from the Internet on: 05.04.2016; URL: http://www.pnas.org/content/102/22/7964.full.pdf, 31 May 2005 (2005/05/31), whole document, page 7969 right hand col. last para., page 7964 right hand col. last para., page 7965 right hand col. last para, page 7966 left hand col. 2nd para., Fig. 2a, 3, 4 * |
| Sarah Ferber PhD, Sheba Medical ctr, Tel Aviv university and Orgenesis Ltd.; "Transdifferentiation And Its Implementation In Autologous Cell Replacement Therapy For Diabetes"; online presentation, pages 1-35; upload date: 29.05.2014. Retrieved from the Internet on: 11.04.2016; URL: http://medical.wesrch.com/paper-details/pdf-MEIXXF8N4RZNR-transdifferentiation-and-its-implementation-in-autologous-cell-replacement-therapy-for-diabetes#page4, 29 May 2014 (2014/05/29), whole document, pages 7, 12, 14, 15, 22, 25, 29, 32, 35 * |
| Yu-ting, A., Wilfred Ip, and Tianru Jin. "The role of the Wnt signaling pathway in incretin hormone production and function." Frontiers in physiology 3 (12.07.2012). Retrieved from the Internet on: 12.04.2016; URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3429047/ 12 Jul 2012 (2012/07/12), page 4 left hand col. 2nd para., page 6 right hand col. last para. - page 8 left hand col. 1st para., Fig. 5 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107750170A (zh) | 2018-03-02 |
| US20200297777A1 (en) | 2020-09-24 |
| EA201791508A1 (ru) | 2018-05-31 |
| KR102487883B1 (ko) | 2023-01-11 |
| CA2972569A1 (en) | 2016-07-07 |
| JP6817943B2 (ja) | 2021-01-20 |
| US11617769B2 (en) | 2023-04-04 |
| EP3240576A4 (en) | 2018-06-20 |
| US10668107B2 (en) | 2020-06-02 |
| AU2015373129B2 (en) | 2021-07-15 |
| SG11201705344VA (en) | 2017-07-28 |
| AU2015373129A1 (en) | 2017-08-03 |
| JP2018502574A (ja) | 2018-02-01 |
| IL253234A0 (en) | 2017-08-31 |
| KR20170102308A (ko) | 2017-09-08 |
| BR112017014280A2 (pt) | 2018-03-27 |
| EP3698803B1 (en) | 2023-03-08 |
| US20160220616A1 (en) | 2016-08-04 |
| CO2017006937A2 (es) | 2017-10-20 |
| EP3240576A1 (en) | 2017-11-08 |
| IL253234B (en) | 2020-04-30 |
| EP3240576B1 (en) | 2020-03-04 |
| EP3698803A1 (en) | 2020-08-26 |
| WO2016108237A1 (en) | 2016-07-07 |
| MX2017008669A (es) | 2018-02-16 |
| US20190134097A1 (en) | 2019-05-09 |
| CN107750170B (zh) | 2021-10-08 |
| US10179151B2 (en) | 2019-01-15 |
| MX378321B (es) | 2025-03-10 |
| MA41296A (fr) | 2017-11-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11617769B2 (en) | Methods of transdifferentiation and methods of use thereof | |
| US10975354B2 (en) | Transdifferentiated cell populations and methods of use thereof | |
| US10947509B2 (en) | Cell populations, methods of transdifferentiation and methods of use thereof | |
| WO2018220623A1 (en) | Compositions and methods for providing cell replacement therapy | |
| WO2015190522A1 (ja) | 内胚葉性幹細胞の製造方法 |