JP2015509381A5 - - Google Patents

Info

Publication number

JP2015509381A5

JP2015509381A5 JP2014561075A JP2014561075A JP2015509381A5 JP 2015509381 A5 JP2015509381 A5 JP 2015509381A5 JP 2014561075 A JP2014561075 A JP 2014561075A JP 2014561075 A JP2014561075 A JP 2014561075A JP 2015509381 A5 JP2015509381 A5 JP 2015509381A5

Authority

JP

Japan

Prior art keywords

acid

cell culture

tgf

ligand

insulin

Prior art date

2013-03-06

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

• 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 48
• 238000009472 formulation Methods 0.000 claims description 31
• 239000000203 mixture Substances 0.000 claims description 31
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 28
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 26
• 108090000379 Fibroblast growth factor 2 Proteins 0.000 claims description 24
• 102000004877 Insulin Human genes 0.000 claims description 24
• 108090001061 Insulin Proteins 0.000 claims description 24
• 229940125396 insulin Drugs 0.000 claims description 24
• BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims description 23
• 102000004338 Transferrin Human genes 0.000 claims description 23
• 108090000901 Transferrin Proteins 0.000 claims description 23
• 239000011669 selenium Substances 0.000 claims description 23
• 229910052711 selenium Inorganic materials 0.000 claims description 23
• 239000012581 transferrin Substances 0.000 claims description 23
• 102100024785 Fibroblast growth factor 2 Human genes 0.000 claims description 22
• 108090001012 Transforming Growth Factor beta Proteins 0.000 claims description 20
• YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 claims description 14
• 239000007640 basal medium Substances 0.000 claims description 14
• 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 claims description 14
• 235000019441 ethanol Nutrition 0.000 claims description 14
• IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 claims description 14
• SECPZKHBENQXJG-FPLPWBNLSA-N palmitoleic acid Chemical compound CCCCCC\C=C/CCCCCCCC(O)=O SECPZKHBENQXJG-FPLPWBNLSA-N 0.000 claims description 14
• FGDZQCVHDSGLHJ-UHFFFAOYSA-M rubidium chloride Chemical compound [Cl-].[Rb+] FGDZQCVHDSGLHJ-UHFFFAOYSA-M 0.000 claims description 14
• 235000010323 ascorbic acid Nutrition 0.000 claims description 13
• 229960005070 ascorbic acid Drugs 0.000 claims description 13
• 239000011668 ascorbic acid Substances 0.000 claims description 13
• 210000004027 cell Anatomy 0.000 claims description 13
• 239000002609 medium Substances 0.000 claims description 12
• 238000000034 method Methods 0.000 claims description 9
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 7
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 7
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 7
• 101710134784 Agnoprotein Proteins 0.000 claims description 7
• 229910005793 GeO 2 Inorganic materials 0.000 claims description 7
• 239000005642 Oleic acid Substances 0.000 claims description 7
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 7
• 235000021314 Palmitic acid Nutrition 0.000 claims description 7
• 235000021319 Palmitoleic acid Nutrition 0.000 claims description 7
• RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 7
• 235000021355 Stearic acid Nutrition 0.000 claims description 7
• DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 claims description 7
• 235000020661 alpha-linolenic acid Nutrition 0.000 claims description 7
• 229940114079 arachidonic acid Drugs 0.000 claims description 7
• 235000021342 arachidonic acid Nutrition 0.000 claims description 7
• 235000012000 cholesterol Nutrition 0.000 claims description 7
• SECPZKHBENQXJG-UHFFFAOYSA-N cis-palmitoleic acid Natural products CCCCCCC=CCCCCCCCC(O)=O SECPZKHBENQXJG-UHFFFAOYSA-N 0.000 claims description 7
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 7
• 229960004488 linolenic acid Drugs 0.000 claims description 7
• KQQKGWQCNNTQJW-UHFFFAOYSA-N linolenic acid Natural products CC=CCCC=CCC=CCCCCCCCC(O)=O KQQKGWQCNNTQJW-UHFFFAOYSA-N 0.000 claims description 7
• WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 claims description 7
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 7
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 7
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 7
• 210000001778 pluripotent stem cell Anatomy 0.000 claims description 7
• 229920001993 poloxamer 188 Polymers 0.000 claims description 7
• 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 7
• 229920000053 polysorbate 80 Polymers 0.000 claims description 7
• 239000008117 stearic acid Substances 0.000 claims description 7
• TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 claims description 7
• OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical compound C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-N 0.000 claims description 6
• ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 claims description 6
• 239000011626 DL-alpha-tocopherylacetate Substances 0.000 claims description 6
• 235000001809 DL-alpha-tocopherylacetate Nutrition 0.000 claims description 6
• 229940042585 tocopherol acetate Drugs 0.000 claims description 6
• 210000001671 embryonic stem cell Anatomy 0.000 claims description 3
• 210000000130 stem cell Anatomy 0.000 claims description 3
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 claims description 2
• 239000003153 chemical reaction reagent Substances 0.000 claims description 2
• 230000035755 proliferation Effects 0.000 claims description 2
• 238000004113 cell culture Methods 0.000 claims 37
• 108010088751 Albumins Proteins 0.000 claims 23
• 102000009027 Albumins Human genes 0.000 claims 23
• 235000014113 dietary fatty acids Nutrition 0.000 claims 23
• 229930195729 fatty acid Natural products 0.000 claims 23
• 239000000194 fatty acid Substances 0.000 claims 23
• 150000004665 fatty acids Chemical class 0.000 claims 23
• 239000003446 ligand Substances 0.000 claims 23
• 102000004887 Transforming Growth Factor beta Human genes 0.000 claims 19
• ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 claims 19
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 claims 18
• 108090000723 Insulin-Like Growth Factor I Proteins 0.000 claims 17
• 102000004218 Insulin-Like Growth Factor I Human genes 0.000 claims 17
• 238000012258 culturing Methods 0.000 claims 7
• 235000021313 oleic acid Nutrition 0.000 claims 6
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 claims 5
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims 5
• 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 claims 5
• 239000008103 glucose Substances 0.000 claims 5
• 235000001727 glucose Nutrition 0.000 claims 5
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 3
• 102000004196 processed proteins & peptides Human genes 0.000 claims 3
• 108090000765 processed proteins & peptides Proteins 0.000 claims 3
• 108010016626 Dipeptides Proteins 0.000 claims 2
• 102000046299 Transforming Growth Factor beta1 Human genes 0.000 claims 2
• 101800002279 Transforming growth factor beta-1 Proteins 0.000 claims 2
• 238000000338 in vitro Methods 0.000 claims 2
• HJCMDXDYPOUFDY-WHFBIAKZSA-N Ala-Gln Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O HJCMDXDYPOUFDY-WHFBIAKZSA-N 0.000 claims 1
• 239000011627 DL-alpha-tocopherol Substances 0.000 claims 1
• 235000001815 DL-alpha-tocopherol Nutrition 0.000 claims 1
• 102100029284 Hepatocyte nuclear factor 3-beta Human genes 0.000 claims 1
• 101001062347 Homo sapiens Hepatocyte nuclear factor 3-beta Proteins 0.000 claims 1
• 101000687905 Homo sapiens Transcription factor SOX-2 Proteins 0.000 claims 1
• -1 TGF- β1 Proteins 0.000 claims 1
• 102100024270 Transcription factor SOX-2 Human genes 0.000 claims 1
• 235000011054 acetic acid Nutrition 0.000 claims 1
• 239000002253 acid Substances 0.000 claims 1
• 229960002648 alanylglutamine Drugs 0.000 claims 1
• 229940107161 cholesterol Drugs 0.000 claims 1
• GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims 1
• 229960004756 ethanol Drugs 0.000 claims 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims 1
• 239000001963 growth medium Substances 0.000 claims 1
• 239000011159 matrix material Substances 0.000 claims 1
• 229960000984 tocofersolan Drugs 0.000 claims 1
• GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 claims 1
• 230000007774 longterm Effects 0.000 description 3
• 108091003079 Bovine Serum Albumin 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
• 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 2
• 229940098773 bovine serum albumin Drugs 0.000 description 2
• 102100030742 Transforming growth factor beta-1 proprotein Human genes 0.000 description 1
• 108010023082 activin A Proteins 0.000 description 1
• 239000012141 concentrate Substances 0.000 description 1
• 239000003636 conditioned culture medium Substances 0.000 description 1
• 230000018109 developmental process Effects 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 108010082117 matrigel Proteins 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 230000023895 stem cell maintenance Effects 0.000 description 1
• 239000011573 trace mineral Substances 0.000 description 1
• 235000013619 trace mineral Nutrition 0.000 description 1