JP2010508846A - 心筋形成を誘発するための方法 - Google Patents
心筋形成を誘発するための方法 Download PDFInfo
- Publication number
- JP2010508846A JP2010508846A JP2009536303A JP2009536303A JP2010508846A JP 2010508846 A JP2010508846 A JP 2010508846A JP 2009536303 A JP2009536303 A JP 2009536303A JP 2009536303 A JP2009536303 A JP 2009536303A JP 2010508846 A JP2010508846 A JP 2010508846A
- Authority
- JP
- Japan
- Prior art keywords
- cells
- cardiomyocytes
- catenin
- cell
- population
- 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
- 238000000034 method Methods 0.000 title claims abstract description 105
- 230000001939 inductive effect Effects 0.000 title claims abstract description 16
- 210000000130 stem cell Anatomy 0.000 claims abstract description 122
- 102000013814 Wnt Human genes 0.000 claims abstract description 78
- 108050003627 Wnt Proteins 0.000 claims abstract description 78
- 210000004413 cardiac myocyte Anatomy 0.000 claims abstract description 69
- 230000011664 signaling Effects 0.000 claims abstract description 45
- 230000004156 Wnt signaling pathway Effects 0.000 claims abstract description 11
- 210000004027 cell Anatomy 0.000 claims description 101
- 108060000903 Beta-catenin Proteins 0.000 claims description 77
- 102000015735 Beta-catenin Human genes 0.000 claims description 77
- 230000014509 gene expression Effects 0.000 claims description 37
- 210000003716 mesoderm Anatomy 0.000 claims description 24
- 239000002773 nucleotide Substances 0.000 claims description 21
- 125000003729 nucleotide group Chemical group 0.000 claims description 21
- 230000001965 increasing effect Effects 0.000 claims description 17
- 230000006698 induction Effects 0.000 claims description 11
- 239000011159 matrix material Substances 0.000 claims description 11
- 239000003446 ligand Substances 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 108010030743 Tropomyosin Proteins 0.000 claims description 6
- 102000005937 Tropomyosin Human genes 0.000 claims description 6
- 238000000338 in vitro Methods 0.000 claims description 5
- 241000702421 Dependoparvovirus Species 0.000 claims description 4
- 108090001027 Troponin Proteins 0.000 claims description 3
- 102000004903 Troponin Human genes 0.000 claims description 3
- 239000002458 cell surface marker Substances 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 230000003612 virological effect Effects 0.000 claims description 3
- 230000001960 triggered effect Effects 0.000 claims description 2
- 230000000747 cardiac effect Effects 0.000 abstract description 75
- 238000011160 research Methods 0.000 abstract description 8
- 239000000126 substance Substances 0.000 abstract description 4
- 230000001225 therapeutic effect Effects 0.000 abstract description 4
- 150000001413 amino acids Chemical group 0.000 description 75
- 235000001014 amino acid Nutrition 0.000 description 53
- 229940024606 amino acid Drugs 0.000 description 53
- 108090000623 proteins and genes Proteins 0.000 description 42
- 239000002243 precursor Substances 0.000 description 25
- 229920001184 polypeptide Polymers 0.000 description 21
- 108090000765 processed proteins & peptides Proteins 0.000 description 21
- 102000004196 processed proteins & peptides Human genes 0.000 description 21
- 230000004069 differentiation Effects 0.000 description 20
- 210000002257 embryonic structure Anatomy 0.000 description 18
- 238000011282 treatment Methods 0.000 description 18
- 201000010099 disease Diseases 0.000 description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 16
- 230000000694 effects Effects 0.000 description 14
- 210000005003 heart tissue Anatomy 0.000 description 14
- 238000011161 development Methods 0.000 description 13
- 230000018109 developmental process Effects 0.000 description 13
- 108091028043 Nucleic acid sequence Proteins 0.000 description 12
- 102100030074 Dickkopf-related protein 1 Human genes 0.000 description 11
- 101710099518 Dickkopf-related protein 1 Proteins 0.000 description 11
- 102100024392 Insulin gene enhancer protein ISL-1 Human genes 0.000 description 11
- 239000002609 medium Substances 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 10
- 108091005957 yellow fluorescent proteins Proteins 0.000 description 10
- 241000282414 Homo sapiens Species 0.000 description 9
- 210000002242 embryoid body Anatomy 0.000 description 9
- 210000005241 right ventricle Anatomy 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 8
- 230000001105 regulatory effect Effects 0.000 description 8
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 238000000926 separation method Methods 0.000 description 7
- 239000013598 vector Substances 0.000 description 7
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 6
- 238000011529 RT qPCR Methods 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 108010090448 insulin gene enhancer binding protein Isl-1 Proteins 0.000 description 6
- 230000010349 pulsation Effects 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 101100203200 Danio rerio shha gene Proteins 0.000 description 5
- 101150070110 Isl1 gene Proteins 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 5
- 101150114527 Nkx2-5 gene Proteins 0.000 description 5
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 5
- 239000004473 Threonine Substances 0.000 description 5
- 101100460507 Xenopus laevis nkx-2.5 gene Proteins 0.000 description 5
- 230000024245 cell differentiation Effects 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 239000013604 expression vector Substances 0.000 description 5
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 210000004165 myocardium Anatomy 0.000 description 5
- 230000037361 pathway Effects 0.000 description 5
- 235000018102 proteins Nutrition 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 101150088976 shh gene Proteins 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 101150115978 tbx5 gene Proteins 0.000 description 5
- 239000013603 viral vector Substances 0.000 description 5
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 4
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 4
- 241000287828 Gallus gallus Species 0.000 description 4
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 4
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 4
- -1 Wnt2b / 13 Proteins 0.000 description 4
- 239000000556 agonist Substances 0.000 description 4
- 238000010009 beating Methods 0.000 description 4
- 230000022131 cell cycle Effects 0.000 description 4
- 239000002299 complementary DNA Substances 0.000 description 4
- 208000029078 coronary artery disease Diseases 0.000 description 4
- 108020001507 fusion proteins Proteins 0.000 description 4
- 102000037865 fusion proteins Human genes 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 208000019622 heart disease Diseases 0.000 description 4
- 210000005240 left ventricle Anatomy 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 102000040430 polynucleotide Human genes 0.000 description 4
- 108091033319 polynucleotide Proteins 0.000 description 4
- 239000002157 polynucleotide Substances 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- 230000002861 ventricular Effects 0.000 description 4
- 101150050047 BHLHE40 gene Proteins 0.000 description 3
- 241000283707 Capra Species 0.000 description 3
- 208000020446 Cardiac disease Diseases 0.000 description 3
- 108010058544 Cyclin D2 Proteins 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- 241000713666 Lentivirus Species 0.000 description 3
- 108010076504 Protein Sorting Signals Proteins 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 108700029229 Transcriptional Regulatory Elements Proteins 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 102000044880 Wnt3A Human genes 0.000 description 3
- 108700013515 Wnt3A Proteins 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- 230000001269 cardiogenic effect Effects 0.000 description 3
- 230000000453 cell autonomous effect Effects 0.000 description 3
- 239000006143 cell culture medium Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 210000001671 embryonic stem cell Anatomy 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 238000007901 in situ hybridization Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 230000000302 ischemic effect Effects 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- 210000001161 mammalian embryo Anatomy 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 230000002107 myocardial effect Effects 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 238000002864 sequence alignment Methods 0.000 description 3
- 230000004936 stimulating effect Effects 0.000 description 3
- 230000002103 transcriptional effect Effects 0.000 description 3
- 241000701161 unidentified adenovirus Species 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- 108010085238 Actins Proteins 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 208000006029 Cardiomegaly Diseases 0.000 description 2
- 102000006312 Cyclin D2 Human genes 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 101100210337 Drosophila melanogaster wntD gene Proteins 0.000 description 2
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 2
- 101000916173 Homo sapiens Catenin beta-1 Proteins 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 208000031309 Hypertrophic Familial Cardiomyopathy Diseases 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- 101150107698 MYH6 gene Proteins 0.000 description 2
- 101150043413 MYH7 gene Proteins 0.000 description 2
- 101150078445 MYOCD gene Proteins 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- 101000916174 Mus musculus Catenin beta-1 Proteins 0.000 description 2
- 101100310648 Mus musculus Sox17 gene Proteins 0.000 description 2
- 208000021642 Muscular disease Diseases 0.000 description 2
- FABQUVYDAXWUQP-UHFFFAOYSA-N N4-(1,3-benzodioxol-5-ylmethyl)-6-(3-methoxyphenyl)pyrimidine-2,4-diamine Chemical compound COC1=CC=CC(C=2N=C(N)N=C(NCC=3C=C4OCOC4=CC=3)C=2)=C1 FABQUVYDAXWUQP-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 108700020796 Oncogene Proteins 0.000 description 2
- 206010038748 Restrictive cardiomyopathy Diseases 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
- 101150019524 WNT2 gene Proteins 0.000 description 2
- 108700020986 Wnt-2 Proteins 0.000 description 2
- 102000052556 Wnt-2 Human genes 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 230000000735 allogeneic effect Effects 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 230000003412 degenerative effect Effects 0.000 description 2
- 201000011257 dilated cardiomyopathy 1B Diseases 0.000 description 2
- 210000001900 endoderm Anatomy 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000010195 expression analysis Methods 0.000 description 2
- 208000012955 familial cardiomyopathy Diseases 0.000 description 2
- 208000004996 familial dilated cardiomyopathy Diseases 0.000 description 2
- 201000006692 familial hypertrophic cardiomyopathy Diseases 0.000 description 2
- 208000024251 familial restrictive cardiomyopathy Diseases 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 101150003286 gata4 gene Proteins 0.000 description 2
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 2
- 210000002064 heart cell Anatomy 0.000 description 2
- 230000004398 heart morphogenesis Effects 0.000 description 2
- 102000056097 human CTNNB1 Human genes 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 208000031225 myocardial ischemia Diseases 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 238000003753 real-time PCR Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 210000002235 sarcomere Anatomy 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 241001430294 unidentified retrovirus Species 0.000 description 2
- 239000004474 valine Substances 0.000 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 description 1
- 101150096411 AXIN2 gene Proteins 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 208000031295 Animal disease Diseases 0.000 description 1
- 241000269350 Anura Species 0.000 description 1
- 241000714230 Avian leukemia virus Species 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 102100035683 Axin-2 Human genes 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 208000002330 Congenital Heart Defects Diseases 0.000 description 1
- 108010051219 Cre recombinase Proteins 0.000 description 1
- 102000016736 Cyclin Human genes 0.000 description 1
- 108050006400 Cyclin Proteins 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000991587 Enterovirus C Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 101710181403 Frizzled Proteins 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 102000027587 GPCRs class F Human genes 0.000 description 1
- 108091008884 GPCRs class F Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 208000013875 Heart injury Diseases 0.000 description 1
- 108091027305 Heteroduplex Proteins 0.000 description 1
- 102100033636 Histone H3.2 Human genes 0.000 description 1
- 102000011787 Histone Methyltransferases Human genes 0.000 description 1
- 108010036115 Histone Methyltransferases Proteins 0.000 description 1
- 102100032801 Histone-lysine N-methyltransferase SMYD1 Human genes 0.000 description 1
- 108010033040 Histones Proteins 0.000 description 1
- 101000708638 Homo sapiens Histone-lysine N-methyltransferase SMYD1 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 108090000362 Lymphotoxin-beta Proteins 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 102100025169 Max-binding protein MNT Human genes 0.000 description 1
- 241000714177 Murine leukemia virus Species 0.000 description 1
- 101000969137 Mus musculus Metallothionein-1 Proteins 0.000 description 1
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
- 241000713883 Myeloproliferative sarcoma virus Species 0.000 description 1
- 108010081823 Myocardin Proteins 0.000 description 1
- 102100030217 Myocardin Human genes 0.000 description 1
- 102100026925 Myosin regulatory light chain 2, ventricular/cardiac muscle isoform Human genes 0.000 description 1
- 108700026495 N-Myc Proto-Oncogene Proteins 0.000 description 1
- 102100030124 N-myc proto-oncogene protein Human genes 0.000 description 1
- 101150032346 NDRG1 gene Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108700005075 Regulator Genes Proteins 0.000 description 1
- 241000714474 Rous sarcoma virus Species 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000713896 Spleen necrosis virus Species 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 108091084789 TCF/LEF family Proteins 0.000 description 1
- 102000043043 TCF/LEF family Human genes 0.000 description 1
- 238000012288 TUNEL assay Methods 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
- 102000013534 Troponin C Human genes 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 108010051583 Ventricular Myosins Proteins 0.000 description 1
- 206010047296 Ventricular hypoplasia Diseases 0.000 description 1
- 101150010310 WNT-4 gene Proteins 0.000 description 1
- 101150109862 WNT-5A gene Proteins 0.000 description 1
- 108700020987 Wnt-1 Proteins 0.000 description 1
- 102000052547 Wnt-1 Human genes 0.000 description 1
- 102000052549 Wnt-3 Human genes 0.000 description 1
- 108700020985 Wnt-3 Proteins 0.000 description 1
- 102000052548 Wnt-4 Human genes 0.000 description 1
- 108700020984 Wnt-4 Proteins 0.000 description 1
- 108700020483 Wnt-5a Proteins 0.000 description 1
- 102000043366 Wnt-5a Human genes 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000011558 animal model by disease Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 238000000149 argon plasma sintering Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000000984 branchial region Anatomy 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 230000002060 circadian Effects 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 208000028831 congenital heart disease Diseases 0.000 description 1
- 238000005138 cryopreservation Methods 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000000254 damaging effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 108700037326 eHAND helix-loop-helix Proteins 0.000 description 1
- 210000003981 ectoderm Anatomy 0.000 description 1
- 230000005014 ectopic expression Effects 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 230000007045 gastrulation Effects 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 210000001654 germ layer Anatomy 0.000 description 1
- 230000000762 glandular Effects 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000005090 green fluorescent protein Substances 0.000 description 1
- 230000009643 growth defect Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 101150118163 h gene Proteins 0.000 description 1
- 101150000808 hand1 gene Proteins 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000008611 intercellular interaction Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 238000007885 magnetic separation Methods 0.000 description 1
- 102000006240 membrane receptors Human genes 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 238000010208 microarray analysis Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000000107 myocyte Anatomy 0.000 description 1
- 108010065781 myosin light chain 2 Proteins 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 238000004091 panning Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 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 1
- 230000000541 pulsatile effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108010054624 red fluorescent protein Proteins 0.000 description 1
- 230000022983 regulation of cell cycle Effects 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000010187 selection method Methods 0.000 description 1
- 230000022379 skeletal muscle tissue development Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 108091006107 transcriptional repressors Proteins 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 101150118885 wif1 gene Proteins 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Cardiology (AREA)
- Cell Biology (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Rheumatology (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Materials For Medical Uses (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US85814506P | 2006-11-09 | 2006-11-09 | |
| PCT/US2007/023588 WO2008060446A2 (en) | 2006-11-09 | 2007-11-09 | Methods for inducing cardiomyogenesis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2010508846A true JP2010508846A (ja) | 2010-03-25 |
| JP2010508846A5 JP2010508846A5 (https=) | 2010-12-24 |
Family
ID=39402201
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009536303A Pending JP2010508846A (ja) | 2006-11-09 | 2007-11-09 | 心筋形成を誘発するための方法 |
Country Status (5)
| Country | Link |
|---|---|
| US (2) | US20100129915A1 (https=) |
| EP (1) | EP2084263A4 (https=) |
| JP (1) | JP2010508846A (https=) |
| CN (1) | CN101573442A (https=) |
| WO (1) | WO2008060446A2 (https=) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016127849A (ja) * | 2010-06-13 | 2016-07-14 | インスティチュート・オブ・バイオフィジックス，チャイニーズ・アカデミー・オブ・サイエンシズ | 幹細胞から心筋細胞を調製するための方法および組成物ならびにその使用 |
| JP2021518113A (ja) * | 2018-03-16 | 2021-08-02 | ザ ボード オブ トラスティーズ オブ ザ レランド スタンフォード ジュニア ユニバーシティー | 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 |
| US11339371B2 (en) | 2012-07-23 | 2022-05-24 | Institute Of Biophysics, Chinese Academy Of Sciences | Method for inducing pluripotent stem cells to differentiate into ventricular myocytes in vitro |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010007031A2 (en) * | 2008-07-14 | 2010-01-21 | Novartis Ag | Methods for improving cardiac differentiation of human embryonic stem cells |
| CN102498399A (zh) * | 2009-05-20 | 2012-06-13 | 卡迪欧参生物科技有限公司 | 哺乳动物细胞的心脏生长潜能的确定方法 |
| EP2499260B1 (en) * | 2009-11-10 | 2017-08-23 | Nestec S.A. | Heart aging biomarkers and methods of use |
| US8951798B2 (en) * | 2011-10-13 | 2015-02-10 | Wisconsin Alumni Research Foundation | Generation of cardiomyocytes from human pluripotent stem cells |
| WO2013159349A1 (en) * | 2012-04-27 | 2013-10-31 | Curegenix Inc. | Method for producing cardiomyocytes |
| EP3065785A4 (en) * | 2013-11-06 | 2017-11-15 | The Texas A&M University System | Cardiac myofibril induction |
| CN108779441A (zh) * | 2016-03-15 | 2018-11-09 | 学校法人庆应义塾 | 由多能干细胞制造心脏祖细胞和心肌细胞的制造方法 |
| CN110448675A (zh) * | 2019-09-20 | 2019-11-15 | 苏州大学 | 一种放射性皮肤损伤防治药物 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004094610A2 (en) * | 2003-04-21 | 2004-11-04 | Baylor College Of Medicine | Wnt as a factor for cardiac myogenesis |
| US20060147435A1 (en) * | 2004-12-30 | 2006-07-06 | Moon Randall T | Methods for regulation of stem cells |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4963489A (en) * | 1987-04-14 | 1990-10-16 | Marrow-Tech, Inc. | Three-dimensional cell and tissue culture system |
| US5919449A (en) * | 1995-05-30 | 1999-07-06 | Diacrin, Inc. | Porcine cardiomyocytes and their use in treatment of insufficient cardiac function |
| CA2296704C (en) * | 1997-07-14 | 2010-10-19 | Osiris Therapeutics, Inc. | Cardiac muscle regeneration using mesenchymal stem cells |
| US20030007954A1 (en) * | 1999-04-12 | 2003-01-09 | Gail K. Naughton | Methods for using a three-dimensional stromal tissue to promote angiogenesis |
| US20040014209A1 (en) * | 2002-01-23 | 2004-01-22 | Lassar Andrew B. | Compositions and methods for modulating cell differentiation |
| US20060030541A1 (en) * | 2002-04-05 | 2006-02-09 | Proskelia | Genes involved in osteogenesis, and methods of use |
| WO2006124356A2 (en) * | 2005-05-16 | 2006-11-23 | The Rockefeller University | Method for isolating dermal papilla cells and uses thereof |
| EP2014766A4 (en) * | 2006-04-28 | 2009-12-02 | Asubio Pharma Co Ltd | METHOD FOR DIFFERENTIATING INDICATION OF A MYOCARDIAL CELL FROM A PLURIPOTENTIAL STEM CELL |
-
2007
- 2007-11-09 WO PCT/US2007/023588 patent/WO2008060446A2/en not_active Ceased
- 2007-11-09 CN CNA2007800488155A patent/CN101573442A/zh active Pending
- 2007-11-09 JP JP2009536303A patent/JP2010508846A/ja active Pending
- 2007-11-09 US US12/513,657 patent/US20100129915A1/en not_active Abandoned
- 2007-11-09 EP EP07867393A patent/EP2084263A4/en not_active Withdrawn
-
2015
- 2015-07-30 US US14/814,452 patent/US20160194608A1/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004094610A2 (en) * | 2003-04-21 | 2004-11-04 | Baylor College Of Medicine | Wnt as a factor for cardiac myogenesis |
| US20060147435A1 (en) * | 2004-12-30 | 2006-07-06 | Moon Randall T | Methods for regulation of stem cells |
Non-Patent Citations (2)
| Title |
|---|
| JPN6012060875; Ｓｔｅｍ Ｃｅｌｌｓ，２００５，２３（１０），ｐ．１４８９-５０１ * |
| JPN6012060878; Ｃｉｒｃ．Ｒｅｓ．，２００５，９７（２），ｐ．１４４-５１ * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016127849A (ja) * | 2010-06-13 | 2016-07-14 | インスティチュート・オブ・バイオフィジックス，チャイニーズ・アカデミー・オブ・サイエンシズ | 幹細胞から心筋細胞を調製するための方法および組成物ならびにその使用 |
| US10590386B2 (en) | 2010-06-13 | 2020-03-17 | Insitute Of Biophysics, Chinese Academy Of Sciences | Methods and compositions for preparing cardiomyocytes from stem cells and uses thereof |
| US11339371B2 (en) | 2012-07-23 | 2022-05-24 | Institute Of Biophysics, Chinese Academy Of Sciences | Method for inducing pluripotent stem cells to differentiate into ventricular myocytes in vitro |
| JP2021518113A (ja) * | 2018-03-16 | 2021-08-02 | ザ ボード オブ トラスティーズ オブ ザ レランド スタンフォード ジュニア ユニバーシティー | 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 |
| US12516293B2 (en) | 2018-03-16 | 2026-01-06 | The Board Of Trustees Of The Leland Stanford Junior University | Reagents and methods with Wnt agonists and bioactive lipids for generating and expanding cardiomyocytes |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2008060446A9 (en) | 2008-07-10 |
| EP2084263A2 (en) | 2009-08-05 |
| US20100129915A1 (en) | 2010-05-27 |
| WO2008060446A2 (en) | 2008-05-22 |
| WO2008060446A3 (en) | 2008-11-13 |
| CN101573442A (zh) | 2009-11-04 |
| EP2084263A4 (en) | 2011-06-22 |
| US20160194608A1 (en) | 2016-07-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7727762B2 (en) | Method of inducing the differentiation of stem cells into myocardial cells | |
| CA2650685C (en) | Method for inducing differentiation of pluripotent stem cells into cardiomyocytes | |
| JP2010508846A (ja) | 心筋形成を誘発するための方法 | |
| US6630349B1 (en) | Trophoblast cell preparations | |
| US20100172883A1 (en) | Methods of generating cardiomyocytes | |
| Tanwar et al. | Gremlin 2 promotes differentiation of embryonic stem cells to atrial fate by activation of the JNK signaling pathway | |
| EA011953B1 (ru) | Pdx1-экспрессирующая энтодерма | |
| US8252583B2 (en) | Method for inducing differentiation into cardiomyocytes using G-CSF | |
| US20240110156A1 (en) | Cardiogenic mesoderm formation regulators | |
| Santos | Cited2 in cardiac development: an inside and outside job | |
| Lopes | InCited2 secrete cardiogenic molecules | |
| Yuan | Atrial cardiomyocytes development from human induced pluripotent stem cells |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20101108 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20101108 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20121126 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130225 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130304 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130325 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130401 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20130326 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130816 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20131113 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20131120 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20131213 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20131220 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20140114 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20140121 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140212 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20140212 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20140516 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20140916 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20141107 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20141107 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20160114 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20160215 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20160314 |