JP2021528083A - インスリン産生膵島細胞を増殖させるための組成物および方法、ならびにそれらの治療的使用 - Google Patents
インスリン産生膵島細胞を増殖させるための組成物および方法、ならびにそれらの治療的使用 Download PDFInfo
- Publication number
- JP2021528083A JP2021528083A JP2020571760A JP2020571760A JP2021528083A JP 2021528083 A JP2021528083 A JP 2021528083A JP 2020571760 A JP2020571760 A JP 2020571760A JP 2020571760 A JP2020571760 A JP 2020571760A JP 2021528083 A JP2021528083 A JP 2021528083A
- Authority
- JP
- Japan
- Prior art keywords
- seq
- amino acid
- acid sequence
- population
- aipc
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 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 title claims abstract description 148
- 102000004877 Insulin Human genes 0.000 title claims abstract description 74
- 108090001061 Insulin Proteins 0.000 title claims abstract description 74
- 229940125396 insulin Drugs 0.000 title claims abstract description 74
- 238000000034 method Methods 0.000 title claims abstract description 52
- 239000000203 mixture Substances 0.000 title claims abstract description 40
- 210000004153 islets of langerhan Anatomy 0.000 title claims description 51
- 230000001225 therapeutic effect Effects 0.000 title description 5
- 239000012190 activator Substances 0.000 claims abstract description 40
- 238000011282 treatment Methods 0.000 claims abstract description 26
- 230000002062 proliferating effect Effects 0.000 claims abstract description 15
- 238000000338 in vitro Methods 0.000 claims abstract description 14
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims abstract description 7
- 150000001413 amino acids Chemical group 0.000 claims description 31
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 23
- 229920001184 polypeptide Polymers 0.000 claims description 22
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 22
- 239000006143 cell culture medium Substances 0.000 claims description 15
- 238000012258 culturing Methods 0.000 claims description 12
- 239000007640 basal medium Substances 0.000 claims description 10
- 239000002771 cell marker Substances 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 5
- 239000013543 active substance Substances 0.000 claims description 4
- 239000000872 buffer Substances 0.000 claims description 4
- 238000007792 addition Methods 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 6
- -1 SEQ ID NO: 2 amino acid Chemical class 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 101100519431 Homo sapiens PDZD2 gene Proteins 0.000 abstract description 38
- 102100025646 PDZ domain-containing protein 2 Human genes 0.000 abstract description 38
- 238000002054 transplantation Methods 0.000 abstract description 13
- 241000124008 Mammalia Species 0.000 abstract description 12
- 208000016222 Pancreatic disease Diseases 0.000 abstract description 7
- 238000001727 in vivo Methods 0.000 abstract description 6
- 208000024691 pancreas disease Diseases 0.000 abstract description 2
- 238000010586 diagram Methods 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 167
- 239000002609 medium Substances 0.000 description 45
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 37
- 239000008103 glucose Substances 0.000 description 37
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 23
- 210000000496 pancreas Anatomy 0.000 description 23
- 230000000638 stimulation Effects 0.000 description 18
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 17
- 102000051325 Glucagon Human genes 0.000 description 16
- 108060003199 Glucagon Proteins 0.000 description 16
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 16
- 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 description 16
- 229960004666 glucagon Drugs 0.000 description 16
- 229960001052 streptozocin Drugs 0.000 description 16
- 125000003275 alpha amino acid group Chemical group 0.000 description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 15
- 241001465754 Metazoa Species 0.000 description 14
- 230000035755 proliferation Effects 0.000 description 14
- 241000699670 Mus sp. Species 0.000 description 13
- 206010012601 diabetes mellitus Diseases 0.000 description 13
- 239000003550 marker Substances 0.000 description 13
- 241000699666 Mus <mouse, genus> Species 0.000 description 12
- 210000004369 blood Anatomy 0.000 description 10
- 239000008280 blood Substances 0.000 description 10
- 201000010099 disease Diseases 0.000 description 10
- 210000000130 stem cell Anatomy 0.000 description 10
- 238000004113 cell culture Methods 0.000 description 9
- 239000012634 fragment Substances 0.000 description 9
- 239000002953 phosphate buffered saline Substances 0.000 description 9
- 239000001963 growth medium Substances 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 230000004044 response Effects 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 238000003556 assay Methods 0.000 description 7
- 230000004069 differentiation Effects 0.000 description 7
- 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 7
- 230000014509 gene expression Effects 0.000 description 7
- 230000002124 endocrine Effects 0.000 description 6
- 210000003462 vein Anatomy 0.000 description 6
- 241000227653 Lycopersicon Species 0.000 description 5
- 235000007688 Lycopersicon esculentum Nutrition 0.000 description 5
- 230000004663 cell proliferation Effects 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 5
- 230000028327 secretion Effects 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- 102000004142 Trypsin Human genes 0.000 description 4
- 108090000631 Trypsin Proteins 0.000 description 4
- DPKHZNPWBDQZCN-UHFFFAOYSA-N acridine orange free base Chemical compound C1=CC(N(C)C)=CC2=NC3=CC(N(C)C)=CC=C3C=C21 DPKHZNPWBDQZCN-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- DZBUGLKDJFMEHC-UHFFFAOYSA-N benzoquinolinylidene Natural products C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 4
- 230000012292 cell migration Effects 0.000 description 4
- 230000003833 cell viability Effects 0.000 description 4
- 239000012091 fetal bovine serum Substances 0.000 description 4
- 238000000684 flow cytometry Methods 0.000 description 4
- 201000001421 hyperglycemia Diseases 0.000 description 4
- 238000007747 plating Methods 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 239000012588 trypsin Substances 0.000 description 4
- 230000035899 viability Effects 0.000 description 4
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 3
- 229930182837 (R)-adrenaline Natural products 0.000 description 3
- UOFGSWVZMUXXIY-UHFFFAOYSA-N 1,5-Diphenyl-3-thiocarbazone Chemical compound C=1C=CC=CC=1N=NC(=S)NNC1=CC=CC=C1 UOFGSWVZMUXXIY-UHFFFAOYSA-N 0.000 description 3
- VDABVNMGKGUPEY-UHFFFAOYSA-N 6-carboxyfluorescein succinimidyl ester Chemical compound C=1C(O)=CC=C2C=1OC1=CC(O)=CC=C1C2(C1=C2)OC(=O)C1=CC=C2C(=O)ON1C(=O)CCC1=O VDABVNMGKGUPEY-UHFFFAOYSA-N 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 102000008186 Collagen Human genes 0.000 description 3
- 108010035532 Collagen Proteins 0.000 description 3
- 102100028554 Dual specificity tyrosine-phosphorylation-regulated kinase 1A Human genes 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- 102100027286 Fanconi anemia group C protein Human genes 0.000 description 3
- 239000012981 Hank's balanced salt solution Substances 0.000 description 3
- 101000838016 Homo sapiens Dual specificity tyrosine-phosphorylation-regulated kinase 1A Proteins 0.000 description 3
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 3
- 229930182816 L-glutamine Natural products 0.000 description 3
- 102000007079 Peptide Fragments Human genes 0.000 description 3
- 108010033276 Peptide Fragments Proteins 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 230000032823 cell division Effects 0.000 description 3
- 229920001436 collagen Polymers 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 229960005139 epinephrine Drugs 0.000 description 3
- 210000001508 eye Anatomy 0.000 description 3
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000003345 hyperglycaemic effect Effects 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 210000004263 induced pluripotent stem cell Anatomy 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 230000003914 insulin secretion Effects 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 230000005012 migration Effects 0.000 description 3
- 238000013508 migration Methods 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 230000008672 reprogramming Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- 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 description 2
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 2
- 108010075254 C-Peptide Proteins 0.000 description 2
- 238000011746 C57BL/6J (JAX™ mouse strain) Methods 0.000 description 2
- 102000012422 Collagen Type I Human genes 0.000 description 2
- 108010022452 Collagen Type I Proteins 0.000 description 2
- 102000029816 Collagenase Human genes 0.000 description 2
- 108060005980 Collagenase Proteins 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 102100027581 Forkhead box protein P3 Human genes 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101001033280 Homo sapiens Cytokine receptor common subunit beta Proteins 0.000 description 2
- 101000861452 Homo sapiens Forkhead box protein P3 Proteins 0.000 description 2
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 2
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- GZCGUPFRVQAUEE-VANKVMQKSA-N aldehydo-L-glucose Chemical compound OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)C=O GZCGUPFRVQAUEE-VANKVMQKSA-N 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 238000002869 basic local alignment search tool Methods 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 238000001516 cell proliferation assay Methods 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 229960002424 collagenase Drugs 0.000 description 2
- 210000004748 cultured cell Anatomy 0.000 description 2
- 238000007876 drug discovery Methods 0.000 description 2
- 210000001671 embryonic stem cell Anatomy 0.000 description 2
- 238000005538 encapsulation Methods 0.000 description 2
- 230000008029 eradication Effects 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 102000055647 human CSF2RB Human genes 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 238000009830 intercalation Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- 238000001000 micrograph Methods 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 210000004923 pancreatic tissue Anatomy 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000004043 responsiveness Effects 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 230000000392 somatic effect Effects 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- 108010059616 Activins Proteins 0.000 description 1
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 1
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 1
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 244000060234 Gmelina philippensis Species 0.000 description 1
- 102100028098 Homeobox protein Nkx-6.1 Human genes 0.000 description 1
- 101001098029 Homo sapiens 40S ribosomal protein S2 Proteins 0.000 description 1
- 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 1
- 101000578254 Homo sapiens Homeobox protein Nkx-6.1 Proteins 0.000 description 1
- 101001139134 Homo sapiens Krueppel-like factor 4 Proteins 0.000 description 1
- 101000687905 Homo sapiens Transcription factor SOX-2 Proteins 0.000 description 1
- 102100026818 Inhibin beta E chain Human genes 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 102100020677 Krueppel-like factor 4 Human genes 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 241000244206 Nematoda Species 0.000 description 1
- 102000007999 Nuclear Proteins Human genes 0.000 description 1
- 108010089610 Nuclear Proteins Proteins 0.000 description 1
- 102000011931 Nucleoproteins Human genes 0.000 description 1
- 108010061100 Nucleoproteins Proteins 0.000 description 1
- 102100035423 POU domain, class 5, transcription factor 1 Human genes 0.000 description 1
- 101710126211 POU domain, class 5, transcription factor 1 Proteins 0.000 description 1
- 102100041030 Pancreas/duodenum homeobox protein 1 Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 101710183548 Pyridoxal 5'-phosphate synthase subunit PdxS Proteins 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 108091027967 Small hairpin RNA Proteins 0.000 description 1
- 206010043276 Teratoma Diseases 0.000 description 1
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical class IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 description 1
- 102100024270 Transcription factor SOX-2 Human genes 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000488 activin Substances 0.000 description 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000003851 biochemical process Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000002737 cell proliferation kit Methods 0.000 description 1
- 230000006041 cell recruitment Effects 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000006329 citrullination Effects 0.000 description 1
- 230000004186 co-expression Effects 0.000 description 1
- 229940096422 collagen type i Drugs 0.000 description 1
- 210000001953 common bile duct Anatomy 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000008393 encapsulating agent Substances 0.000 description 1
- 210000004039 endoderm cell Anatomy 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 238000011124 ex vivo culture Methods 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000005558 fluorometry Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 230000002641 glycemic effect Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 102000044741 human RPS2 Human genes 0.000 description 1
- 230000000774 hypoallergenic effect Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000002687 intercalation Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000013028 medium composition Substances 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000002503 metabolic effect Effects 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
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 238000004452 microanalysis Methods 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000009437 off-target effect Effects 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 210000003101 oviduct Anatomy 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000009038 pharmacological inhibition Effects 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- 210000001778 pluripotent stem cell Anatomy 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- VXPLXMJHHKHSOA-UHFFFAOYSA-N propham Chemical compound CC(C)OC(=O)NC1=CC=CC=C1 VXPLXMJHHKHSOA-UHFFFAOYSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000009256 replacement therapy Methods 0.000 description 1
- 229930002330 retinoic acid Natural products 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 210000001082 somatic cell Anatomy 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 239000005495 thyroid hormone Substances 0.000 description 1
- 229940036555 thyroid hormone Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/37—Digestive system
- A61K35/39—Pancreas; Islets of Langerhans
-
- 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
-
- 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
- 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
- C12N5/0677—Three-dimensional culture, tissue culture or organ culture; Encapsulated 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
- 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
- C12N5/0678—Stem cells; Progenitor cells; Precursor 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
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/998—Proteins not provided for elsewhere
-
- 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
- C12N2533/00—Supports or coatings for cell culture, characterised by material
- C12N2533/50—Proteins
- C12N2533/54—Collagen; Gelatin
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Biotechnology (AREA)
- Zoology (AREA)
- Cell Biology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Developmental Biology & Embryology (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Immunology (AREA)
- Physiology (AREA)
- Nutrition Science (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
【選択図】 図11
Description
Smith & Waterman,Adv.Appl.Math.2:482,1981;Needleman & Wunsch,J.Mol.Biol.48:443,1970;Pearson & Lipman,Proc.Nat.Acad Sci.USA 85:2444,1988;Higgins & Sharp, Gene,73:23744,1988;Higgins & Sharp,CABIOS 5:151−3,1989;Corpet et al.,Nuc.Acids Res.16:10881−90,1988; Huang et al.Computer Appls.in the Biosciences 8,155−65,1992;and Pearson et al.,Meth Mol.Bio.24:307−31,1994.Altschul et al.,J.Mol.Biol.215:403−10,1990,presents a detailed consideration of sequence alignment methods and homology calculations.The level of sequence identity may be determined using the NCBI Basic Local Alignment Search Tool(BLAST)(Altschul et al.,J.Mol.Biol.215:403−10,1990),which is available from several sources,including the National Center for Biological Information(NCBI,National Library of Medicine, Building 38A,Room 8N805,Bethesda,Md.20894,US)and on the Internet.
[実施例]
実施例で実施した細胞培養は、標準的なCO2(5%)条件下において37℃でインキュベートした;培養(細胞のメッキ、細胞の分割)は、垂直層流フード中で標準的な無菌技術および条件の下で、およびそれを使用して実施した。別段の記載がない限り、AIPCは表に記載された培地で培養した。AIPCは、培養中に約70〜80%のコンフルエントに達したときに分割された。
Claims (18)
- 活性化膵島増殖細胞(AIPC)集団を生成する方法であって、
前記AIPC集団を得るために、基底培地及び有効量の活性剤を含む細胞培養培地を使って膵島の集団をインビトロで培養する工程を含み、
前記AIPC集団の少なくとも60%は、CD133細胞マーカーおよびKi−67細胞マーカーからなり、
前記AIPC集団の少なくとも60%は、インスリン産生することが可能であり、および
前記活性剤は、配列ID番号:1〜4のいずれか1つと少なくとも50%の配列同一性を有するポリペプチドを含む、方法。 - 請求項1記載の方法において、前記膵島の集団は、約10〜約10,000個の膵島を含む、方法。
- 請求項1〜2いずれか1項記載の方法において、前記培養は、約2日〜約10日の期間で行われる、方法。
- 請求項1〜3いずれか1項記載の方法において、前記AIPC集団の少なくとも約80%は、インスリン、CD133、およびKi−67に陽性である、方法。
- 請求項1〜4いずれか1項記載の方法において、前記ポリペプチドは、少なくとも、配列ID番号:1記載のアミノ酸配列に対して95%の配列同一性、配列ID番号:1記載のアミノ酸配列に対して98%の配列同一性、配列ID番号:1記載のアミノ酸配列に対して99%の配列同一性、配列ID番号:1記載のアミノ酸配列、配列ID番号:2記載のアミノ酸配列に対して95%の配列同一性、配列ID番号:2記載のアミノ酸配列に対して98%の配列同一性、配列ID番号:2記載のアミノ酸配列に対して99%の配列同一性、配列ID番号:2記載のアミノ酸配列、配列ID番号:3記載のアミノ酸配列に対して95%の配列同一性、配列ID番号:3記載のアミノ酸配列に対して98%の配列同一性、配列ID番号:3記載のアミノ酸配列に対して99%の配列同一性、配列ID番号:3記載のアミノ酸配列、配列ID番号:4記載のアミノ酸配列に対して95%の配列同一性、配列ID番号:4記載のアミノ酸配列に対して98%の配列同一性、配列ID番号:4記載のアミノ酸配列に対して99%の配列同一性、または配列ID番号:4記載のアミノ酸配列を含む、方法。
- 請求項1〜5いずれか1項記載の方法において、前記細胞培養培地は、約1μg/mL〜約20μg/mLの濃度で活性剤を含む、方法。
- 請求項1〜6いずれか1項記載の方法において、前記細胞培養培地は、約5μg/mL〜約15μg/mLの濃度で活性剤を含む、方法。
- 活性化膵島増殖細胞(AIPC)集団を含む組成物であって、前記AIPC集団の60%は、CD133細胞マーカーおよびKi−67細胞マーカーで構成され、
前記AIPC集団の少なくとも60%は、インスリン産生することが可能である、組成物。 - 請求項8記載の組成物において、前記AIPC集団は、直列通過可能であり、培養中に60日以上生存可能なままである、組成物。
- 請求項8〜9いずれか1項記載の方法であって、1またはそれ以上の緩衝液、1またはそれ以上の薬学的に許容される担体、または1またはそれ以上の薬学的に許容される添加剤をさらに含む、組成物。
- 工程によって得られた活性化膵島増殖細胞(AIPC)集団を含む組成物であって、
前記AIPC集団を得るために、基底培地および有効量の活性剤を含む細胞培養培地を使って、単離された膵臓細胞集団をインビトロで培養する工程を含み、
前記AIPC集団の少なくとも30%は、CD133細胞マーカーおよびKi−67細胞マーカーからなり、
前記AIPC集団の少なくとも60%がインスリン産生することが可能であり、
前記活性剤は、配列ID番号:1〜4のいずれか1つと少なくとも50%の配列同一性を有するポリペプチドを含む、組成物。 - 請求項12記載の組成物において、前記AIPC集団は、直列通過可能であり、培養中に少なくとも60日間生存可能なままである、組成物。
- 請求項12〜13いずれか1項記載の組成物において、前記膵島の集団は、約10〜約10,000個の膵島を含む、組成物。
- 請求項12〜14いずれか1項記載の組成物において、前記培養する工程は、約2日〜約10日の期間にわたって行われる、組成物。
- 請求項12〜15のいずれか1項記載の組成物において、前記AIPC集団の少なくとも約80%がインスリン、CD133、およびKi−67に対して陽性である、組成物。
- 請求項12〜16のいずれか1項記載の組成物であって、前記ポリペプチドは、少なくとも、配列ID番号:1記載のアミノ酸配列に対して95%の配列同一性、配列ID番号:1記載のアミノ酸配列に対して98%の配列同一性、配列ID番号:1記載のアミノ酸配列に対して99%の配列同一性、配列ID番号:1記載のアミノ酸配列、配列ID番号:2記載のアミノ酸配列に対して95%の配列同一性、配列ID番号:2記載のアミノ酸配列に対して98%の配列同一性、配列ID番号:2記載のアミノ酸配列に対して99%の配列同一性、配列ID番号:2記載のアミノ酸配列、配列ID番号:3記載のアミノ酸配列に対して95%の配列同一性、配列ID番号:3記載のアミノ酸配列に対して98%の配列同一性、配列ID番号:3記載のアミノ酸配列に対して99%の配列同一性、配列ID番号:3記載のアミノ酸配列、配列ID番号:4記載のアミノ酸配列に対して95%の配列同一性、配列ID番号:4記載のアミノ酸配列に対して98%の配列同一性、配列ID番号:4記載のアミノ酸配列に対して99%の配列同一性、または配列ID番号:4記載のアミノ酸配列を含む、組成物。
- 請求項12〜17のいずれか1項記載の組成物において、前記細胞培養培地は、約1μg/mL〜約20μg/mL、または約5μg/mL〜約15μg/mLの濃度で活性剤を構成する、組成物。
- I型糖尿病の治療に使用するための、請求項8〜17のいずれか1項記載の組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201862689780P | 2018-06-25 | 2018-06-25 | |
US62/689,780 | 2018-06-25 | ||
PCT/US2019/038305 WO2020005721A1 (en) | 2018-06-25 | 2019-06-20 | Compositions and methods for propagating insulin-producing islet cells and therapeutic uses thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2021528083A true JP2021528083A (ja) | 2021-10-21 |
JPWO2020005721A5 JPWO2020005721A5 (ja) | 2022-10-28 |
Family
ID=68987391
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020571760A Pending JP2021528083A (ja) | 2018-06-25 | 2019-06-20 | インスリン産生膵島細胞を増殖させるための組成物および方法、ならびにそれらの治療的使用 |
Country Status (10)
Country | Link |
---|---|
US (1) | US20210205371A1 (ja) |
EP (1) | EP3810174A4 (ja) |
JP (1) | JP2021528083A (ja) |
KR (1) | KR20210024557A (ja) |
CN (1) | CN113015537A (ja) |
AU (1) | AU2019295576B2 (ja) |
BR (1) | BR112020026531A2 (ja) |
CA (1) | CA3104901A1 (ja) |
MX (1) | MX2020014242A (ja) |
WO (1) | WO2020005721A1 (ja) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2023049079A2 (en) * | 2021-09-22 | 2023-03-30 | Imagine Pharma Llc | Compositions and methods for propogating insulin and glucagon secreting cells from type 1 diabetic pancreatic tissue and therapeutic uses thereof |
CN115197893A (zh) * | 2022-06-30 | 2022-10-18 | 成都中科奥格生物科技有限公司 | 一种胰岛细胞培养基及其应用 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010509936A (ja) * | 2006-11-21 | 2010-04-02 | ロジャー・ウィリアムズ・ホスピタル | 膵島細胞の長期培養のための骨髄細胞の使用 |
WO2018089909A1 (en) * | 2016-11-13 | 2018-05-17 | Imagine Pharma | Compositions and methods for treating diabetes, hypertension and hypercholesterolemia |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006094286A2 (en) * | 2005-03-04 | 2006-09-08 | John O'neil | Adult pancreatic derived stromal cells |
JP2011509076A (ja) * | 2007-12-28 | 2011-03-24 | ノボ・ノルデイスク・エー/エス | 膵臓内分泌細胞の前駆体を介した該細胞のddr1媒介性細胞精製 |
CN104583392A (zh) * | 2012-08-22 | 2015-04-29 | 耶达研究与发展有限公司 | 分离不同胰腺细胞类型的方法 |
-
2019
- 2019-06-20 US US17/256,141 patent/US20210205371A1/en active Pending
- 2019-06-20 MX MX2020014242A patent/MX2020014242A/es unknown
- 2019-06-20 JP JP2020571760A patent/JP2021528083A/ja active Pending
- 2019-06-20 BR BR112020026531-4A patent/BR112020026531A2/pt unknown
- 2019-06-20 CN CN201980055757.1A patent/CN113015537A/zh active Pending
- 2019-06-20 AU AU2019295576A patent/AU2019295576B2/en active Active
- 2019-06-20 KR KR1020217001618A patent/KR20210024557A/ko unknown
- 2019-06-20 CA CA3104901A patent/CA3104901A1/en active Pending
- 2019-06-20 WO PCT/US2019/038305 patent/WO2020005721A1/en unknown
- 2019-06-20 EP EP19825538.2A patent/EP3810174A4/en active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010509936A (ja) * | 2006-11-21 | 2010-04-02 | ロジャー・ウィリアムズ・ホスピタル | 膵島細胞の長期培養のための骨髄細胞の使用 |
WO2018089909A1 (en) * | 2016-11-13 | 2018-05-17 | Imagine Pharma | Compositions and methods for treating diabetes, hypertension and hypercholesterolemia |
Non-Patent Citations (4)
Title |
---|
JIMENEZ-PALOMARES ET AL., AM. J. PHYSIOL. ENDOCRINOL. METAB., vol. 308, JPN7023001693, 13 January 2015 (2015-01-13), pages 450 - 459, ISSN: 0005049547 * |
LEE ET AL., ELIFE, vol. 2, JPN7023001692, 19 November 2013 (2013-11-19), pages 00940, ISSN: 0005049546 * |
MA ET AL., STEM CELL RESEARCH & THERAPY, vol. 8, JPN7023001690, 26 July 2017 (2017-07-26), pages 172, ISSN: 0005049545 * |
SONG ET AL., INT. J. MOL. SCI., vol. 19, JPN7023001691, 22 March 2018 (2018-03-22), pages 943, ISSN: 0005049544 * |
Also Published As
Publication number | Publication date |
---|---|
AU2019295576B2 (en) | 2024-04-04 |
AU2019295576A1 (en) | 2021-01-28 |
US20210205371A1 (en) | 2021-07-08 |
KR20210024557A (ko) | 2021-03-05 |
EP3810174A1 (en) | 2021-04-28 |
CA3104901A1 (en) | 2020-01-02 |
BR112020026531A2 (pt) | 2021-04-06 |
WO2020005721A1 (en) | 2020-01-02 |
EP3810174A4 (en) | 2022-05-11 |
MX2020014242A (es) | 2021-05-27 |
CN113015537A (zh) | 2021-06-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Planat-Benard et al. | Spontaneous cardiomyocyte differentiation from adipose tissue stroma cells | |
US20150368618A1 (en) | Modulation of cardiac stem-progenitor cell differentiation, assays and uses thereof | |
WO2011101834A1 (en) | A method for obtaining mesenchymal stem cells, media, methods and composition thereof | |
EP2558137B1 (en) | Methods and combination | |
CZ2004696A3 (cs) | Endokrinní pankreatická diferenciace buněk stromatu odvozených z adipózní tkáně a její použití | |
Kassem et al. | Exendin-4 enhances the differentiation of Wharton’s jelly mesenchymal stem cells into insulin-producing cells through activation of various β-cell markers | |
TWI438275B (zh) | 促進幹細胞分化為胰島素製造細胞的方法 | |
JP2021528083A (ja) | インスリン産生膵島細胞を増殖させるための組成物および方法、ならびにそれらの治療的使用 | |
Jawahar et al. | Ductal cell reprogramming to insulin-producing beta-like cells as a potential beta cell replacement source for chronic pancreatitis | |
JP2013521797A (ja) | 膵由来非内分泌上皮細胞と血管内皮細胞との組織複合体による膵島様組織の培養法 | |
TW201000110A (en) | Method of differentiating mammalian progenitor cells into insulin producing pancreatic islet cells | |
JP7465506B2 (ja) | 褐色脂肪細胞上清、その調製法、及び、使用 | |
Li et al. | Islet neogenesis-associated protein-related pentadecapeptide enhances the differentiation of islet-like clusters from human pancreatic duct cells | |
Ishii et al. | Technical advantage of recombinant collagenase for isolation of muscle stem cells | |
WO2020035480A1 (en) | Viable pancreatic islet-like cell structures and a method of preparing thereof | |
Umezawa et al. | Proliferative activity of skeletal myoblast sheet by paracrine effects of mesenchymal stem cells | |
RU2430158C1 (ru) | Способ дифференцировки стволовых клеток взрослого человека в клетки, секретирующие инсулин | |
Chandravanshi et al. | Reprogramming mouse embryo fibroblasts to functional islets without genetic manipulation | |
Pittenger et al. | A role for islet neogenesis in curing diabetes | |
CN112522181A (zh) | 体外诱导产生人胰岛β细胞的培养基体系及方法 | |
Wang et al. | α-Cell loss from islet impairs its insulin secretion in vitro and in vivo | |
WO2023190941A1 (ja) | 培養由来成分を含まない角膜内皮細胞製剤及びその製造法 | |
CA3231258A1 (en) | Compositions and methods for propogating insulin and glucagon secreting cells from type 1 diabetic pancreatic tissue and therapeutic uses thereof | |
KR20240073018A (ko) | 제1형 당뇨병 췌장 조직으로부터 인슐린 분비 세포 및 글루카곤 분비 세포를 번식시키기 위한 조성물과 방법 및 이들의 치료적 용도 | |
吉元利仁 | Effect of mesenchymal cells on myoblast sheets embedded in collagen gel |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220613 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20220613 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20221018 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20230419 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230502 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20230729 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20230929 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20231031 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20240123 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20240513 |