JPWO2019157329A5 - - Google Patents

Info

Publication number

JPWO2019157329A5

JPWO2019157329A5 JP2020542885A JP2020542885A JPWO2019157329A5 JP WO2019157329 A5 JPWO2019157329 A5 JP WO2019157329A5 JP 2020542885 A JP2020542885 A JP 2020542885A JP 2020542885 A JP2020542885 A JP 2020542885A JP WO2019157329 A5 JPWO2019157329 A5 JP WO2019157329A5

Authority

JP

Japan

Prior art keywords

cells

culturing

cell

cyclopamine

retinoic acid

Prior art date

2022-02-15

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Granted

Links

• Espacenet
• Global Dossier
• Discuss

• 210000004027 cell Anatomy 0.000 claims description 74
• 238000000034 method Methods 0.000 claims description 73
• 210000000130 stem cell Anatomy 0.000 claims description 61
• 239000002609 medium Substances 0.000 claims description 39
• 238000012258 culturing Methods 0.000 claims description 23
• 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 claims description 22
• 229930002330 retinoic acid Natural products 0.000 claims description 22
• 229960001727 tretinoin Drugs 0.000 claims description 22
• QASFUMOKHFSJGL-LAFRSMQTSA-N Cyclopamine Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H](CC2=C3C)[C@@H]1[C@@H]2CC[C@@]13O[C@@H]2C[C@H](C)CN[C@H]2[C@H]1C QASFUMOKHFSJGL-LAFRSMQTSA-N 0.000 claims description 21
• QASFUMOKHFSJGL-UHFFFAOYSA-N cyclopamine Natural products C1C=C2CC(O)CCC2(C)C(CC2=C3C)C1C2CCC13OC2CC(C)CNC2C1C QASFUMOKHFSJGL-UHFFFAOYSA-N 0.000 claims description 21
• 102000003972 Fibroblast growth factor 7 Human genes 0.000 claims description 12
• 108090000385 Fibroblast growth factor 7 Proteins 0.000 claims description 12
• 210000004039 endoderm cell Anatomy 0.000 claims description 12
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 12
• 210000003890 endocrine cell Anatomy 0.000 claims description 9
• 210000002660 insulin-secreting cell Anatomy 0.000 claims description 7
• 102000004877 Insulin Human genes 0.000 claims description 6
• 108090001061 Insulin Proteins 0.000 claims description 6
• 229940125396 insulin Drugs 0.000 claims description 6
• QDLHCMPXEPAAMD-QAIWCSMKSA-N wortmannin Chemical compound C1([C@]2(C)C3=C(C4=O)OC=C3C(=O)O[C@@H]2COC)=C4[C@@H]2CCC(=O)[C@@]2(C)C[C@H]1OC(C)=O QDLHCMPXEPAAMD-QAIWCSMKSA-N 0.000 claims description 6
• 239000000853 adhesive Substances 0.000 claims description 5
• 230000001070 adhesive effect Effects 0.000 claims description 5
• 238000004519 manufacturing process Methods 0.000 claims description 5
• 210000004923 pancreatic tissue Anatomy 0.000 claims description 5
• 239000000758 substrate Substances 0.000 claims description 5
• 108090000723 Insulin-Like Growth Factor I Proteins 0.000 claims description 4
• 108010023082 activin A Proteins 0.000 claims description 4
• 230000004069 differentiation Effects 0.000 claims description 4
• 241000124008 Mammalia Species 0.000 claims description 3
• 102000044880 Wnt3A Human genes 0.000 claims description 3
• 108700013515 Wnt3A Proteins 0.000 claims description 3
• JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 0.000 claims description 3
• -1 nogin Proteins 0.000 claims description 3
• 238000004114 suspension culture Methods 0.000 claims description 3
• 102000004218 Insulin-Like Growth Factor I Human genes 0.000 claims description 2
• 230000001464 adherent effect Effects 0.000 claims description 2
• 239000001963 growth medium Substances 0.000 claims description 2
• KRGPXXHMOXVMMM-UHFFFAOYSA-N nicotianamine Natural products OC(=O)C(N)CCNC(C(O)=O)CCN1CCC1C(O)=O KRGPXXHMOXVMMM-UHFFFAOYSA-N 0.000 claims 1
• 239000000203 mixture Substances 0.000 description 16
• 210000001900 endoderm Anatomy 0.000 description 8
• 108090000623 proteins and genes Proteins 0.000 description 8
• 230000008672 reprogramming Effects 0.000 description 8
• 230000001939 inductive effect Effects 0.000 description 6
• VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 4
• 102000009024 Epidermal Growth Factor Human genes 0.000 description 3
• 101800003838 Epidermal growth factor Proteins 0.000 description 3
• 102100039171 Heat shock protein beta-2 Human genes 0.000 description 3
• 101000974015 Homo sapiens Nucleosome assembly protein 1-like 1 Proteins 0.000 description 3
• 101000933386 Homo sapiens S-methylmethionine-homocysteine S-methyltransferase BHMT2 Proteins 0.000 description 3
• 101150081092 Hspb2 gene Proteins 0.000 description 3
• 102100022389 Nucleosome assembly protein 1-like 1 Human genes 0.000 description 3
• 102100025992 S-methylmethionine-homocysteine S-methyltransferase BHMT2 Human genes 0.000 description 3
• 229940116977 epidermal growth factor Drugs 0.000 description 3
• 230000001105 regulatory effect Effects 0.000 description 3
• 101000623873 Homo sapiens Metaxin-3 Proteins 0.000 description 2
• 101000577964 Homo sapiens Protein MIX23 Proteins 0.000 description 2
• 101000723969 Homo sapiens Putative protein ZBED10P Proteins 0.000 description 2
• 101000857273 Homo sapiens Zinc finger protein GLIS2 Proteins 0.000 description 2
• 102000014429 Insulin-like growth factor Human genes 0.000 description 2
• 108700021430 Kruppel-Like Factor 4 Proteins 0.000 description 2
• 102100023139 Metaxin-3 Human genes 0.000 description 2
• 101710126211 POU domain, class 5, transcription factor 1 Proteins 0.000 description 2
• 102100028174 Protein MIX23 Human genes 0.000 description 2
• 102100028242 Putative protein ZBED10P Human genes 0.000 description 2
• 101100247004 Rattus norvegicus Qsox1 gene Proteins 0.000 description 2
• 102100025884 Zinc finger protein GLIS2 Human genes 0.000 description 2
• 210000001671 embryonic stem cell Anatomy 0.000 description 2
• 230000002124 endocrine Effects 0.000 description 2
• 239000013613 expression plasmid Substances 0.000 description 2
• 210000004263 induced pluripotent stem cell Anatomy 0.000 description 2
• PCTLYGKHPBZRCZ-UKLTVQOFSA-N maitotoxin-3 Chemical compound C[C@H]1CC[C@H]2O[C@@]3(C)C[C@H]4O[C@H]5C[C@H]6O[C@](O)(C[C@@H](O)CO)[C@@H](O)[C@@H](OS(O)(=O)=O)[C@@H]6O[C@@H]5C=C[C@@H]4O[C@@H]3CC[C@@H]2O[C@@H]2C[C@@H]3O[C@]4(C)CC(=C)C[C@](C)(O[C@H]4C[C@H]3O[C@@H]12)[C@@H](O)CC(=O)CC\C=C(/C)C=C PCTLYGKHPBZRCZ-UKLTVQOFSA-N 0.000 description 2
• LUEWUZLMQUOBSB-FSKGGBMCSA-N (2s,3s,4s,5s,6r)-2-[(2r,3s,4r,5r,6s)-6-[(2r,3s,4r,5s,6s)-4,5-dihydroxy-2-(hydroxymethyl)-6-[(2r,4r,5s,6r)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-4,5-dihydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound O[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@@H](O[C@@H]2[C@H](O[C@@H](OC3[C@H](O[C@@H](O)[C@@H](O)[C@H]3O)CO)[C@@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O LUEWUZLMQUOBSB-FSKGGBMCSA-N 0.000 description 1
• FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
• 229920002581 Glucomannan Polymers 0.000 description 1
• 102100028098 Homeobox protein Nkx-6.1 Human genes 0.000 description 1
• 101000578254 Homo sapiens Homeobox protein Nkx-6.1 Proteins 0.000 description 1
• 102100032063 Neurogenic differentiation factor 1 Human genes 0.000 description 1
• 108050000588 Neurogenic differentiation factor 1 Proteins 0.000 description 1
• 238000001190 Q-PCR Methods 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 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
• 229940072056 alginate Drugs 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 206010012601 diabetes mellitus Diseases 0.000 description 1
• 229940046240 glucomannan Drugs 0.000 description 1
• 210000003716 mesoderm Anatomy 0.000 description 1
• 238000010208 microarray analysis Methods 0.000 description 1
• 229960002715 nicotine Drugs 0.000 description 1
• SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
• 238000002054 transplantation Methods 0.000 description 1