CN113924359A - 通过番茄次碱处理促进干细胞分化为成熟心肌细胞的方法 - Google Patents
通过番茄次碱处理促进干细胞分化为成熟心肌细胞的方法 Download PDFInfo
- Publication number
- CN113924359A CN113924359A CN202080040203.7A CN202080040203A CN113924359A CN 113924359 A CN113924359 A CN 113924359A CN 202080040203 A CN202080040203 A CN 202080040203A CN 113924359 A CN113924359 A CN 113924359A
- Authority
- CN
- China
- Prior art keywords
- cardiomyocytes
- stem cells
- solanesoximine
- differentiated
- composition
- 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
- 210000004027 cell Anatomy 0.000 title claims abstract description 52
- 210000000130 stem cell Anatomy 0.000 title claims abstract description 40
- 238000000034 method Methods 0.000 title claims abstract description 30
- 230000002107 myocardial effect Effects 0.000 title abstract description 8
- 230000001737 promoting effect Effects 0.000 title abstract description 6
- 235000007688 Lycopersicon esculentum Nutrition 0.000 title description 17
- 240000003768 Solanum lycopersicum Species 0.000 title description 17
- 210000004413 cardiac myocyte Anatomy 0.000 claims abstract description 162
- 230000004069 differentiation Effects 0.000 claims abstract description 48
- 230000035800 maturation Effects 0.000 claims abstract description 23
- 239000003814 drug Substances 0.000 claims abstract description 12
- AFPLNGZPBSKHHQ-UHFFFAOYSA-N Betulaprenol 9 Natural products CC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCO AFPLNGZPBSKHHQ-UHFFFAOYSA-N 0.000 claims abstract description 9
- AFPLNGZPBSKHHQ-MEGGAXOGSA-N solanesol Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CO AFPLNGZPBSKHHQ-MEGGAXOGSA-N 0.000 claims abstract description 9
- 208000019622 heart disease Diseases 0.000 claims abstract description 8
- 229940124597 therapeutic agent Drugs 0.000 claims abstract description 7
- 108090000623 proteins and genes Proteins 0.000 claims description 28
- 210000005239 tubule Anatomy 0.000 claims description 25
- 230000001939 inductive effect Effects 0.000 claims description 24
- 102100026925 Myosin regulatory light chain 2, ventricular/cardiac muscle isoform Human genes 0.000 claims description 20
- 102000004169 proteins and genes Human genes 0.000 claims description 17
- 101000629029 Homo sapiens Myosin regulatory light chain 2, ventricular/cardiac muscle isoform Proteins 0.000 claims description 16
- 238000012258 culturing Methods 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 14
- WRKPZSMRWPJJDH-UHFFFAOYSA-N N-(6-methyl-1,3-benzothiazol-2-yl)-2-[(4-oxo-3-phenyl-6,7-dihydrothieno[3,2-d]pyrimidin-2-yl)thio]acetamide Chemical compound S1C2=CC(C)=CC=C2N=C1NC(=O)CSC1=NC=2CCSC=2C(=O)N1C1=CC=CC=C1 WRKPZSMRWPJJDH-UHFFFAOYSA-N 0.000 claims description 13
- 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
- 230000000747 cardiac effect Effects 0.000 claims description 11
- 239000013028 medium composition Substances 0.000 claims description 11
- 102000005604 Myosin Heavy Chains Human genes 0.000 claims description 10
- 108010051583 Ventricular Myosins Proteins 0.000 claims description 10
- AQGNHMOJWBZFQQ-UHFFFAOYSA-N CT 99021 Chemical compound CC1=CNC(C=2C(=NC(NCCNC=3N=CC(=CC=3)C#N)=NC=2)C=2C(=CC(Cl)=CC=2)Cl)=N1 AQGNHMOJWBZFQQ-UHFFFAOYSA-N 0.000 claims description 6
- 101000614614 Homo sapiens Junctophilin-2 Proteins 0.000 claims description 6
- 101000958741 Homo sapiens Myosin-6 Proteins 0.000 claims description 6
- 101001030243 Homo sapiens Myosin-7 Proteins 0.000 claims description 6
- 102000004877 Insulin Human genes 0.000 claims description 6
- 108090001061 Insulin Proteins 0.000 claims description 6
- 102100040503 Junctophilin-2 Human genes 0.000 claims description 6
- 102100038319 Myosin-6 Human genes 0.000 claims description 6
- 102100038934 Myosin-7 Human genes 0.000 claims description 6
- 101100537532 Rattus norvegicus Tnni3 gene Proteins 0.000 claims description 6
- 229940125396 insulin Drugs 0.000 claims description 6
- 239000002243 precursor Substances 0.000 claims description 6
- 101001120813 Homo sapiens Myosin regulatory light chain 2, atrial isoform Proteins 0.000 claims description 5
- 102100026057 Myosin regulatory light chain 2, atrial isoform Human genes 0.000 claims description 5
- 108010085238 Actins Proteins 0.000 claims description 4
- 102000007469 Actins Human genes 0.000 claims description 4
- 108010084085 Atrial Myosins Proteins 0.000 claims description 4
- 102000004987 Troponin T Human genes 0.000 claims description 4
- 108090001108 Troponin T Proteins 0.000 claims description 4
- 108020001621 Natriuretic Peptide Proteins 0.000 claims description 3
- 102000004571 Natriuretic peptide Human genes 0.000 claims description 3
- 108090001027 Troponin Proteins 0.000 claims description 3
- 102000004903 Troponin Human genes 0.000 claims description 3
- 102000006495 integrins Human genes 0.000 claims description 3
- 108010044426 integrins Proteins 0.000 claims description 3
- 239000000692 natriuretic peptide Substances 0.000 claims description 3
- 239000013589 supplement Substances 0.000 claims description 3
- 230000000694 effects Effects 0.000 abstract description 9
- 229940079593 drug Drugs 0.000 abstract description 4
- 208000010125 myocardial infarction Diseases 0.000 abstract description 3
- 206010048610 Cardiotoxicity Diseases 0.000 abstract description 2
- 231100000259 cardiotoxicity Toxicity 0.000 abstract description 2
- 238000011156 evaluation Methods 0.000 abstract description 2
- 238000012360 testing method Methods 0.000 abstract description 2
- 239000002609 medium Substances 0.000 description 25
- 210000001671 embryonic stem cell Anatomy 0.000 description 21
- XYNPYHXGMWJBLV-VXPJTDKGSA-N Tomatidine Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CC[C@H](O)C[C@@H]4CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@@]11CC[C@H](C)CN1 XYNPYHXGMWJBLV-VXPJTDKGSA-N 0.000 description 18
- 239000003550 marker Substances 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 230000001965 increasing effect Effects 0.000 description 9
- 239000003112 inhibitor Substances 0.000 description 8
- 108091007911 GSKs Proteins 0.000 description 7
- 102000004103 Glycogen Synthase Kinases Human genes 0.000 description 7
- 239000012980 RPMI-1640 medium Substances 0.000 description 7
- 210000001778 pluripotent stem cell Anatomy 0.000 description 7
- 230000011664 signaling Effects 0.000 description 7
- 238000001262 western blot Methods 0.000 description 7
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 6
- 101710172711 Structural protein Proteins 0.000 description 6
- 230000008602 contraction Effects 0.000 description 6
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 6
- 239000002547 new drug Substances 0.000 description 6
- 239000012583 B-27 Supplement Substances 0.000 description 5
- 238000012790 confirmation Methods 0.000 description 5
- 210000004263 induced pluripotent stem cell Anatomy 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 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 4
- KNLOWJPFLKGYGQ-UHFFFAOYSA-N Solasodine 3-O-??-L-rhamnopyranosyl (1‘Â∆2)-O-[??-D-glucopyranosyl (1‘Â∆4)]-??-D-glucopyranoside Natural products O1C2(NCC(C)CC2)C(C)C(C2(CCC3C4(C)CC5)C)C1CC2C3CC=C4CC5OC(C(C1O)OC2C(C(O)C(O)C(C)O2)O)OC(CO)C1OC1OC(CO)C(O)C(O)C1O KNLOWJPFLKGYGQ-UHFFFAOYSA-N 0.000 description 4
- QCTMYNGDIBTNSK-UHFFFAOYSA-N Solasonin Natural products O1C2(NCC(C)CC2)C(C)C(C2(CCC3C4(C)CC5)C)C1CC2C3CC=C4CC5OC(C1OC2C(C(O)C(O)C(C)O2)O)OC(CO)C(O)C1OC1OC(CO)C(O)C(O)C1O QCTMYNGDIBTNSK-UHFFFAOYSA-N 0.000 description 4
- QCTMYNGDIBTNSK-QCNFCIKQSA-N Solasonine Natural products O([C@@H]1[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@@H](O)[C@H](C)O2)[C@@H](O[C@@H]2CC=3[C@@](C)([C@@H]4[C@H]([C@H]5[C@@](C)([C@H]6[C@@H](C)[C@@]7(O[C@H]6C5)NC[C@H](C)CC7)CC4)CC=3)CC2)O[C@@H](CO)[C@@H]1O)[C@H]1[C@@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 QCTMYNGDIBTNSK-QCNFCIKQSA-N 0.000 description 4
- 102000013814 Wnt Human genes 0.000 description 4
- 108050003627 Wnt Proteins 0.000 description 4
- RCTKRNCKOYYRIO-UHFFFAOYSA-N alpha-Solamarine Natural products O1C2(NCC(C)CC2)C(C)C(C2(CCC3C4(C)CC5)C)C1CC2C3CC=C4CC5OC(C1O)OC(CO)C(O)C1OC1OC(CO)C(O)C(O)C1OC1OC(C)C(O)C(O)C1O RCTKRNCKOYYRIO-UHFFFAOYSA-N 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 238000000684 flow cytometry Methods 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 238000012762 unpaired Student’s t-test Methods 0.000 description 4
- QCTMYNGDIBTNSK-XEAAVONHSA-N α-Solamarine Chemical compound O([C@H]1[C@@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@H](O)[C@@H](O)[C@H](C)O1)O)O[C@@H]1CC2=CC[C@H]3[C@@H]4C[C@H]5[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@@H]([C@]1(NC[C@H](C)CC1)O5)C)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O QCTMYNGDIBTNSK-XEAAVONHSA-N 0.000 description 4
- IXFSUSNUALIXLU-UHFFFAOYSA-N 3-[4-[2-[6-(dioctylamino)naphthalen-2-yl]ethenyl]pyridin-1-ium-1-yl]propane-1-sulfonate Chemical compound C1=CC2=CC(N(CCCCCCCC)CCCCCCCC)=CC=C2C=C1C=CC1=CC=[N+](CCCS([O-])(=O)=O)C=C1 IXFSUSNUALIXLU-UHFFFAOYSA-N 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 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 229930040373 Paraformaldehyde Natural products 0.000 description 3
- 238000000692 Student's t-test Methods 0.000 description 3
- GZCGUPFRVQAUEE-SLPGGIOYSA-N aldehydo-D-glucose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O GZCGUPFRVQAUEE-SLPGGIOYSA-N 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 239000000411 inducer Substances 0.000 description 3
- 235000014655 lactic acid Nutrition 0.000 description 3
- 239000004310 lactic acid Substances 0.000 description 3
- 229920002866 paraformaldehyde Polymers 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- XYNPYHXGMWJBLV-OFMODGJOSA-N tomatidine Natural products O[C@@H]1C[C@H]2[C@@](C)([C@@H]3[C@H]([C@H]4[C@@](C)([C@H]5[C@@H](C)[C@]6(O[C@H]5C4)NC[C@@H](C)CC6)CC3)CC2)CC1 XYNPYHXGMWJBLV-OFMODGJOSA-N 0.000 description 3
- WQZGKKKJIJFFOK-SVZMEOIVSA-N (+)-Galactose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-N 0.000 description 2
- BHLYRWXGMIUIHG-HNNXBMFYSA-N (S)-reticuline Chemical compound C1=C(O)C(OC)=CC=C1C[C@H]1C2=CC(O)=C(OC)C=C2CCN1C BHLYRWXGMIUIHG-HNNXBMFYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000020446 Cardiac disease Diseases 0.000 description 2
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 2
- 208000031229 Cardiomyopathies Diseases 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 208000026214 Skeletal muscle atrophy Diseases 0.000 description 2
- 229930013930 alkaloid Natural products 0.000 description 2
- RXVGBQCEAQZMLW-UHFFFAOYSA-N alpha-solanine Natural products CC1CCC2C(C)C3C(CC4C5CC=C6CC(CCC6(C)C5CCC34C)OC7OC(CO)C(O)C(OC8OC(CO)C(O)C(O)C8O)C7OC9OC(CO)C(O)C(O)C9O)N2C1 RXVGBQCEAQZMLW-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 230000003205 diastolic effect Effects 0.000 description 2
- 238000009509 drug development Methods 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 238000003125 immunofluorescent labeling Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 230000033001 locomotion Effects 0.000 description 2
- 238000000386 microscopy Methods 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 210000004165 myocardium Anatomy 0.000 description 2
- 238000012758 nuclear staining Methods 0.000 description 2
- 238000001543 one-way ANOVA Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 238000003753 real-time PCR Methods 0.000 description 2
- 210000002235 sarcomere Anatomy 0.000 description 2
- PWRIIDWSQYQFQD-UHFFFAOYSA-N sisunine Natural products CC1CCC2(NC1)OC3CC4C5CCC6CC(CCC6(C)C5CCC4(C)C3C2C)OC7OC(CO)C(OC8OC(CO)C(O)C(OC9OC(CO)C(O)C(O)C9OC%10OC(CO)C(O)C(O)C%10O)C8O)C(O)C7O PWRIIDWSQYQFQD-UHFFFAOYSA-N 0.000 description 2
- 230000025185 skeletal muscle atrophy Effects 0.000 description 2
- ZGVSETXHNHBTRK-OTYSSXIJSA-N solanine Chemical compound O([C@H]1[C@@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@@H]1[C@@H]([C@H](O)[C@@H](O)[C@H](C)O1)O)O[C@@H]1CC2=CC[C@H]3[C@@H]4C[C@@H]5N6C[C@@H](C)CC[C@@H]6[C@H]([C@@H]5[C@@]4(C)CC[C@@H]3[C@@]2(C)CC1)C)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O ZGVSETXHNHBTRK-OTYSSXIJSA-N 0.000 description 2
- 229940031352 solanine Drugs 0.000 description 2
- 230000003637 steroidlike Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 231100000820 toxicity test Toxicity 0.000 description 2
- RUPUUZZJJXCDHS-UHFFFAOYSA-N (+)-orientaline Natural products C1=C(O)C(OC)=CC(CC2C3=CC(O)=C(OC)C=C3CCN2C)=C1 RUPUUZZJJXCDHS-UHFFFAOYSA-N 0.000 description 1
- XDIYNQZUNSSENW-UUBOPVPUSA-N (2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O XDIYNQZUNSSENW-UUBOPVPUSA-N 0.000 description 1
- NTSBZVCEIVPKBJ-UHFFFAOYSA-N 1-azakenpaullone Chemical compound C1C(=O)NC2=CC=CN=C2C2=C1C1=CC(Br)=CC=C1N2 NTSBZVCEIVPKBJ-UHFFFAOYSA-N 0.000 description 1
- VKWMGUNWDFIWNW-UHFFFAOYSA-N 2-chloro-1,1-dioxo-1,2-benzothiazol-3-one Chemical compound C1=CC=C2S(=O)(=O)N(Cl)C(=O)C2=C1 VKWMGUNWDFIWNW-UHFFFAOYSA-N 0.000 description 1
- 239000012103 Alexa Fluor 488 Substances 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 101800001288 Atrial natriuretic factor Proteins 0.000 description 1
- 101800001890 Atrial natriuretic peptide Proteins 0.000 description 1
- 101100149536 Caenorhabditis elegans skn-1 gene Proteins 0.000 description 1
- 108090000312 Calcium Channels Proteins 0.000 description 1
- 102000003922 Calcium Channels Human genes 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000006029 Cardiomegaly Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000588302 Homo sapiens Nuclear factor erythroid 2-related factor 2 Proteins 0.000 description 1
- 101000837136 Homo sapiens Tenascin-N Proteins 0.000 description 1
- 101000819074 Homo sapiens Transcription factor GATA-4 Proteins 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 206010048858 Ischaemic cardiomyopathy Diseases 0.000 description 1
- 102000004016 L-Type Calcium Channels Human genes 0.000 description 1
- 108090000420 L-Type Calcium Channels Proteins 0.000 description 1
- 102000008135 Mechanistic Target of Rapamycin Complex 1 Human genes 0.000 description 1
- 108010035196 Mechanistic Target of Rapamycin Complex 1 Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 102000003505 Myosin Human genes 0.000 description 1
- 108060008487 Myosin Proteins 0.000 description 1
- 101150114527 Nkx2-5 gene Proteins 0.000 description 1
- 102100031701 Nuclear factor erythroid 2-related factor 2 Human genes 0.000 description 1
- 241000146226 Physalis ixocarpa Species 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 101100083855 Rattus norvegicus Pou2f3 gene Proteins 0.000 description 1
- 229930001406 Ryanodine Natural products 0.000 description 1
- 102100038803 Somatotropin Human genes 0.000 description 1
- 102100028651 Tenascin-N Human genes 0.000 description 1
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical compound 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
- QMGSCYSTMWRURP-UHFFFAOYSA-N Tomatine Natural products CC1CCC2(NC1)OC3CC4C5CCC6CC(CCC6(C)C5CCC4(C)C3C2C)OC7OC(CO)C(OC8OC(CO)C(O)C(OC9OCC(O)C(O)C9OC%10OC(CO)C(O)C(O)C%10O)C8O)C(O)C7O QMGSCYSTMWRURP-UHFFFAOYSA-N 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 102100021380 Transcription factor GATA-4 Human genes 0.000 description 1
- 230000004156 Wnt signaling pathway Effects 0.000 description 1
- 101100460507 Xenopus laevis nkx-2.5 gene Proteins 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000036982 action potential Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 230000004900 autophagic degradation Effects 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000012888 bovine serum Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000027902 cell growth involved in cardiac muscle cell development Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000002144 chemical decomposition reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000012136 culture method Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 201000005219 extrinsic cardiomyopathy Diseases 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000000984 immunochemical effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 201000007170 intrinsic cardiomyopathy Diseases 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000005087 leaf formation Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 108010082117 matrigel Proteins 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000002284 membrane microdomain Anatomy 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 210000002894 multi-fate stem cell Anatomy 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 230000002644 neurohormonal effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 150000007523 nucleic acids Chemical group 0.000 description 1
- 210000002747 omentum Anatomy 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- BNUZUOWRDKPBQR-UHFFFAOYSA-N reticuline Natural products CN1CCC2=CC(OC)=CC=C2C1CC1=CC=C(OC)C(O)=C1 BNUZUOWRDKPBQR-UHFFFAOYSA-N 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- JJSYXNQGLHBRRK-SFEDZAPPSA-N ryanodine Chemical compound O([C@@H]1[C@]([C@@]2([C@]3(O)[C@]45O[C@@]2(O)C[C@]([C@]4(CC[C@H](C)[C@H]5O)O)(C)[C@@]31O)C)(O)C(C)C)C(=O)C1=CC=CN1 JJSYXNQGLHBRRK-SFEDZAPPSA-N 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 229930003352 steroid alkaloid Natural products 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- REJLGAUYTKNVJM-SGXCCWNXSA-N tomatine Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@H]1[C@@H](CO)O[C@H]([C@@H]([C@H]1O)O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4C[C@H]5[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@@H]([C@@]1(NC[C@@H](C)CC1)O5)C)[C@@H]1OC[C@@H](O)[C@H](O)[C@H]1O REJLGAUYTKNVJM-SGXCCWNXSA-N 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 210000002444 unipotent stem cell Anatomy 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- 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
- C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
- C12N5/0657—Cardiomyocytes; Heart cells
-
- 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
- A61K35/34—Muscles; Smooth muscle cells; Heart; Cardiac stem cells; Myoblasts; Myocytes; Cardiomyocytes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- 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
- C12N2501/40—Regulators of development
- C12N2501/415—Wnt; Frizzeled
-
- 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
- C12N2501/70—Enzymes
- C12N2501/72—Transferases (EC 2.)
- C12N2501/727—Kinases (EC 2.7.)
-
- 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
- C12N2501/999—Small molecules 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
- C12N2506/00—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells
- C12N2506/02—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from embryonic cells
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Wood Science & Technology (AREA)
- Developmental Biology & Embryology (AREA)
- Genetics & Genomics (AREA)
- Virology (AREA)
- Vascular Medicine (AREA)
- Immunology (AREA)
- General Chemical & Material Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR10-2019-0062579 | 2019-05-28 | ||
KR1020190062579A KR102167257B1 (ko) | 2019-05-28 | 2019-05-28 | 토마티딘 처리를 통한 줄기세포의 성숙화된 심근세포로의 분화유도 촉진 방법 |
PCT/KR2020/004841 WO2020242045A1 (fr) | 2019-05-28 | 2020-04-09 | Procédé pour favoriser la différenciation de cellules souches en cardiomyocytes matures par un traitement avec de la tomatidine |
Publications (1)
Publication Number | Publication Date |
---|---|
CN113924359A true CN113924359A (zh) | 2022-01-11 |
Family
ID=73042827
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202080040203.7A Pending CN113924359A (zh) | 2019-05-28 | 2020-04-09 | 通过番茄次碱处理促进干细胞分化为成熟心肌细胞的方法 |
Country Status (3)
Country | Link |
---|---|
KR (1) | KR102167257B1 (fr) |
CN (1) | CN113924359A (fr) |
WO (1) | WO2020242045A1 (fr) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20230152192A (ko) | 2022-04-21 | 2023-11-03 | 주식회사 스마트셀랩 | 커큐민에 의한 줄기세포의 심근전구세포로의 유도 및 심근세포로의 분화 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20160177267A1 (en) * | 2014-12-18 | 2016-06-23 | President And Fellows Of Harvard College | Serum-free in vitro directed differentiation protocol for generating stem cell-derived beta cells and uses thereof |
WO2018170280A1 (fr) * | 2017-03-15 | 2018-09-20 | University Of Washington | Méthodes et compositions pour améliorer la maturation et la prise de greffe de cardiomyocytes |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP4950660B2 (ja) * | 2003-06-27 | 2012-06-13 | エチコン、インコーポレイテッド | 分娩後由来細胞を使用する眼組織の修復および再生 |
US10913929B2 (en) * | 2009-10-13 | 2021-02-09 | Stemcell Technologies Inc. | Method of differentiating stem cells |
CN106414718A (zh) * | 2013-06-11 | 2017-02-15 | 哈佛学院校长同事会 | SC-β细胞以及用于产生其的组合物和方法 |
KR102604999B1 (ko) * | 2014-09-08 | 2023-11-23 | 고쿠리쓰 겐큐 가이하쓰 호징 리가가쿠 겐큐소 | 소뇌 선구체 조직의 제조 방법 |
-
2019
- 2019-05-28 KR KR1020190062579A patent/KR102167257B1/ko active IP Right Grant
-
2020
- 2020-04-09 WO PCT/KR2020/004841 patent/WO2020242045A1/fr active Application Filing
- 2020-04-09 CN CN202080040203.7A patent/CN113924359A/zh active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20160177267A1 (en) * | 2014-12-18 | 2016-06-23 | President And Fellows Of Harvard College | Serum-free in vitro directed differentiation protocol for generating stem cell-derived beta cells and uses thereof |
WO2018170280A1 (fr) * | 2017-03-15 | 2018-09-20 | University Of Washington | Méthodes et compositions pour améliorer la maturation et la prise de greffe de cardiomyocytes |
Non-Patent Citations (3)
Title |
---|
PARIKH SS ET AL.: "hyroid and Glucocorticoid Hormones Promote Functional T-Tubule Development in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes", 《CIRC RES.》, 8 December 2017 (2017-12-08), pages 1323 - 1330 * |
SILVA DOS SANTOS DET AL.: "Embryonic stem cell-derived cardiomyocytes for the treatment of doxorubicin-induced cardiomyopathy", 《STEM CELL RES THER.》, vol. 9, no. 1, 5 February 2018 (2018-02-05) * |
傅继东: "分化发育早期心肌细胞钙稳态的调控——应用胚胎干细胞向心肌细胞分化体外模型的基础研究", 《中国优秀博硕士学位论文全文数据库 (博士)基础科学辑》, 15 October 2006 (2006-10-15) * |
Also Published As
Publication number | Publication date |
---|---|
WO2020242045A1 (fr) | 2020-12-03 |
KR102167257B1 (ko) | 2020-10-19 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7386290B2 (ja) | ヒト心室前駆細胞の生着のための遺伝子マーカー | |
Rupert et al. | IGF1 and NRG1 enhance proliferation, metabolic maturity, and the force‐frequency response in hESC‐derived engineered cardiac tissues | |
TWI720333B (zh) | 多能性幹細胞的製備方法、使用該製備方法而製備出多能性幹細胞、改善劑、以及該多能性幹細胞之分化誘導方法 | |
CN106459922B (zh) | Cd82阳性心肌前体细胞 | |
AU2017314870A1 (en) | Cardiomyocyte maturation | |
JP7275109B2 (ja) | ニューロピリン-1(nrp1)のヒト心室前駆細胞を単離するための細胞表面マーカーとしての使用 | |
EP3183337B1 (fr) | Utilisation de jagged 1/frizzled 4 à titre de marqueurs de surface cellulaire pour isoler des cellules progénitrices ventriculaires cardiaques humaines | |
CN105518125A (zh) | 用于产生心外膜细胞的方法和组合物 | |
WO2013063305A2 (fr) | Différenciation dirigée en cardiomyocytes de cellules souches | |
KR101562366B1 (ko) | 메타크릴레이트화된 젤라틴을 포함하는, 심근세포분화 유도용 세포 지지체 | |
JP2024037905A (ja) | 心筋細胞を生成及び増殖させるためのwntアゴニスト、並びに生理活性脂質を用いた試薬及び方法 | |
WO2015081094A1 (fr) | Cellules progénitrices cardiaques et leurs procédés d'utilisation | |
US9155765B2 (en) | Establishment of patient- or person-specific cardiac myocyte cell lines from human induced pluripotent stem cells (iPSCs) | |
CN113924359A (zh) | 通过番茄次碱处理促进干细胞分化为成熟心肌细胞的方法 | |
KR101539132B1 (ko) | 유전자 도입 없이 저분자성 물질을 이용하여 체세포로부터 심근세포를 유도하는 방법 | |
US7534607B1 (en) | Method of producing cardiomyocytes from mesenchymal stem cells | |
Di Felice et al. | OPLA scaffold, collagen I, and horse serum induce a higher degree of myogenic differentiation of adult rat cardiac stem cells | |
Liu et al. | A net-shaped multicellular formation facilitates the maturation of hPSC-derived cardiomyocytes through mechanical and electrophysiological stimuli | |
JP2016077159A (ja) | 心筋細胞の製造方法、心室型心筋細胞及びその製造方法、並びにスクリーニング方法 | |
JP2010246476A (ja) | 心筋細胞分化誘導促進剤およびその使用方法 | |
WO2017177050A1 (fr) | Reprogrammation directe de cellules somatiques en cellules myogènes | |
Xue et al. | Angiotensin II promotes differentiation of mouse c-kit-positive cardiac stem cells into pacemaker-like cells | |
JPWO2005116194A1 (ja) | 試験管内筋繊維形成のための筋芽細胞又は筋芽細胞様細胞培養法 | |
Feige | Molecular Regulation of Satellite Cell Fate | |
Hoes | Studying cardiac diseases using human stem cell-derived cardiomyocytes |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination |