KR102558606B1 - 결장 유사장기 및 이를 제조 및 사용하는 방법 - Google Patents
결장 유사장기 및 이를 제조 및 사용하는 방법 Download PDFInfo
- Publication number
- KR102558606B1 KR102558606B1 KR1020197018724A KR20197018724A KR102558606B1 KR 102558606 B1 KR102558606 B1 KR 102558606B1 KR 1020197018724 A KR1020197018724 A KR 1020197018724A KR 20197018724 A KR20197018724 A KR 20197018724A KR 102558606 B1 KR102558606 B1 KR 102558606B1
- Authority
- KR
- South Korea
- Prior art keywords
- cells
- hco
- bmp
- signaling pathway
- colon
- 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.)
- Active
Links
- 238000000034 method Methods 0.000 title claims abstract description 71
- 210000001072 colon Anatomy 0.000 title claims description 83
- 210000000056 organ Anatomy 0.000 title description 29
- 210000002220 organoid Anatomy 0.000 claims abstract description 97
- 230000019491 signal transduction Effects 0.000 claims abstract description 49
- 210000001900 endoderm Anatomy 0.000 claims abstract description 43
- 230000000112 colonic effect Effects 0.000 claims abstract description 42
- 210000000130 stem cell Anatomy 0.000 claims abstract description 39
- 238000000338 in vitro Methods 0.000 claims abstract description 25
- 201000010099 disease Diseases 0.000 claims abstract description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 14
- 206010009944 Colon cancer Diseases 0.000 claims abstract description 10
- 206010009887 colitis Diseases 0.000 claims abstract description 7
- 208000029742 colonic neoplasm Diseases 0.000 claims abstract description 7
- 229940124606 potential therapeutic agent Drugs 0.000 claims abstract description 7
- 231100000419 toxicity Toxicity 0.000 claims abstract description 7
- 230000001988 toxicity Effects 0.000 claims abstract description 7
- 208000015768 polyposis Diseases 0.000 claims abstract description 6
- 208000002551 irritable bowel syndrome Diseases 0.000 claims abstract description 5
- 208000011580 syndromic disease Diseases 0.000 claims abstract description 5
- 210000004027 cell Anatomy 0.000 claims description 127
- 230000014509 gene expression Effects 0.000 claims description 80
- 108090000623 proteins and genes Proteins 0.000 claims description 60
- 102100032883 DNA-binding protein SATB2 Human genes 0.000 claims description 55
- 101000655236 Homo sapiens DNA-binding protein SATB2 Proteins 0.000 claims description 55
- 239000012190 activator Substances 0.000 claims description 46
- 230000000968 intestinal effect Effects 0.000 claims description 46
- 101000762366 Homo sapiens Bone morphogenetic protein 2 Proteins 0.000 claims description 43
- 102100024506 Bone morphogenetic protein 2 Human genes 0.000 claims description 42
- 210000001671 embryonic stem cell Anatomy 0.000 claims description 31
- 210000004263 induced pluripotent stem cell Anatomy 0.000 claims description 31
- 210000003750 lower gastrointestinal tract Anatomy 0.000 claims description 31
- 210000001519 tissue Anatomy 0.000 claims description 30
- 108010083123 CDX2 Transcription Factor Proteins 0.000 claims description 27
- 102000004169 proteins and genes Human genes 0.000 claims description 26
- 101150021185 FGF gene Proteins 0.000 claims description 25
- 102000009024 Epidermal Growth Factor Human genes 0.000 claims description 22
- 210000002175 goblet cell Anatomy 0.000 claims description 21
- 150000003384 small molecules Chemical group 0.000 claims description 17
- -1 2-amino-4,6-disubstituted pyrimidines Chemical class 0.000 claims description 15
- 101000998774 Homo sapiens Insulin-like peptide INSL5 Proteins 0.000 claims description 15
- 102100033266 Insulin-like peptide INSL5 Human genes 0.000 claims description 15
- 230000004156 Wnt signaling pathway Effects 0.000 claims description 14
- 239000003112 inhibitor Substances 0.000 claims description 14
- 230000037361 pathway Effects 0.000 claims description 14
- 210000004602 germ cell Anatomy 0.000 claims description 13
- 102000001267 GSK3 Human genes 0.000 claims description 10
- 210000004039 endoderm cell Anatomy 0.000 claims description 10
- 210000003158 enteroendocrine cell Anatomy 0.000 claims description 10
- 230000001939 inductive effect Effects 0.000 claims description 10
- 102100028072 Fibroblast growth factor 4 Human genes 0.000 claims description 9
- 101001060274 Homo sapiens Fibroblast growth factor 4 Proteins 0.000 claims description 9
- 230000015572 biosynthetic process Effects 0.000 claims description 9
- 239000005556 hormone Substances 0.000 claims description 9
- 229940088597 hormone Drugs 0.000 claims description 9
- 108060006662 GSK3 Proteins 0.000 claims description 8
- NFVJNJQRWPQVOA-UHFFFAOYSA-N n-[2-chloro-5-(trifluoromethyl)phenyl]-2-[3-(4-ethyl-5-ethylsulfanyl-1,2,4-triazol-3-yl)piperidin-1-yl]acetamide Chemical compound CCN1C(SCC)=NN=C1C1CN(CC(=O)NC=2C(=CC=C(C=2)C(F)(F)F)Cl)CCC1 NFVJNJQRWPQVOA-UHFFFAOYSA-N 0.000 claims description 8
- 239000002775 capsule Substances 0.000 claims description 7
- 108060000903 Beta-catenin Proteins 0.000 claims description 6
- 102000015735 Beta-catenin Human genes 0.000 claims description 6
- 102100024505 Bone morphogenetic protein 4 Human genes 0.000 claims description 6
- 102000006277 CDX2 Transcription Factor Human genes 0.000 claims description 6
- 101000762379 Homo sapiens Bone morphogenetic protein 4 Proteins 0.000 claims description 6
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 claims description 6
- 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 5
- 102100035290 Fibroblast growth factor 13 Human genes 0.000 claims description 5
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 claims description 5
- 102100028043 Fibroblast growth factor 3 Human genes 0.000 claims description 4
- 101001060280 Homo sapiens Fibroblast growth factor 3 Proteins 0.000 claims description 4
- 206010061598 Immunodeficiency Diseases 0.000 claims description 4
- IPICFSFUAKDZEI-UHFFFAOYSA-N 3-methyl-2-[2-[[3-methyl-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyloxy]butanoyl]amino]propanoyloxy]butanoic acid Chemical compound CC(C)C(C(O)=O)OC(=O)C(C)NC(=O)C(C(C)C)OC(=O)C(C)NC(=O)OC(C)(C)C IPICFSFUAKDZEI-UHFFFAOYSA-N 0.000 claims description 3
- 101800001382 Betacellulin Proteins 0.000 claims description 3
- 102100022544 Bone morphogenetic protein 7 Human genes 0.000 claims description 3
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 claims description 3
- 102000003971 Fibroblast Growth Factor 1 Human genes 0.000 claims description 3
- 102100028412 Fibroblast growth factor 10 Human genes 0.000 claims description 3
- 102100028413 Fibroblast growth factor 11 Human genes 0.000 claims description 3
- 102100028417 Fibroblast growth factor 12 Human genes 0.000 claims description 3
- 102100035292 Fibroblast growth factor 14 Human genes 0.000 claims description 3
- 102100035307 Fibroblast growth factor 16 Human genes 0.000 claims description 3
- 108050002072 Fibroblast growth factor 16 Proteins 0.000 claims description 3
- 102100035308 Fibroblast growth factor 17 Human genes 0.000 claims description 3
- 102100035323 Fibroblast growth factor 18 Human genes 0.000 claims description 3
- 102100031734 Fibroblast growth factor 19 Human genes 0.000 claims description 3
- 102100031361 Fibroblast growth factor 20 Human genes 0.000 claims description 3
- 108090000376 Fibroblast growth factor 21 Proteins 0.000 claims description 3
- 102000003973 Fibroblast growth factor 21 Human genes 0.000 claims description 3
- 102100024804 Fibroblast growth factor 22 Human genes 0.000 claims description 3
- 102100040892 Growth/differentiation factor 2 Human genes 0.000 claims description 3
- 101000899361 Homo sapiens Bone morphogenetic protein 7 Proteins 0.000 claims description 3
- 101000917237 Homo sapiens Fibroblast growth factor 10 Proteins 0.000 claims description 3
- 101000917236 Homo sapiens Fibroblast growth factor 11 Proteins 0.000 claims description 3
- 101000917234 Homo sapiens Fibroblast growth factor 12 Proteins 0.000 claims description 3
- 101000878181 Homo sapiens Fibroblast growth factor 14 Proteins 0.000 claims description 3
- 101000878124 Homo sapiens Fibroblast growth factor 17 Proteins 0.000 claims description 3
- 101000878128 Homo sapiens Fibroblast growth factor 18 Proteins 0.000 claims description 3
- 101000846394 Homo sapiens Fibroblast growth factor 19 Proteins 0.000 claims description 3
- 101000846532 Homo sapiens Fibroblast growth factor 20 Proteins 0.000 claims description 3
- 101001051971 Homo sapiens Fibroblast growth factor 22 Proteins 0.000 claims description 3
- 101000893585 Homo sapiens Growth/differentiation factor 2 Proteins 0.000 claims description 3
- 101100390675 Mus musculus Fgf15 gene Proteins 0.000 claims description 3
- 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 claims description 3
- 108010072083 NSC 668036 Proteins 0.000 claims description 3
- 241000283984 Rodentia Species 0.000 claims description 3
- 101150010310 WNT-4 gene Proteins 0.000 claims description 3
- 101150109862 WNT-5A gene Proteins 0.000 claims description 3
- 101150019524 WNT2 gene Proteins 0.000 claims description 3
- 108700020987 Wnt-1 Proteins 0.000 claims description 3
- 102000052547 Wnt-1 Human genes 0.000 claims description 3
- 108700020986 Wnt-2 Proteins 0.000 claims description 3
- 102000052556 Wnt-2 Human genes 0.000 claims description 3
- 102000052549 Wnt-3 Human genes 0.000 claims description 3
- 108700020985 Wnt-3 Proteins 0.000 claims description 3
- 102000052548 Wnt-4 Human genes 0.000 claims description 3
- 108700020984 Wnt-4 Proteins 0.000 claims description 3
- 108700020483 Wnt-5a Proteins 0.000 claims description 3
- 102000043366 Wnt-5a Human genes 0.000 claims description 3
- 101100485097 Xenopus laevis wnt11b gene Proteins 0.000 claims description 3
- 102000003684 fibroblast growth factor 13 Human genes 0.000 claims description 3
- 108090000047 fibroblast growth factor 13 Proteins 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 210000003734 kidney Anatomy 0.000 claims description 3
- 210000001704 mesoblast Anatomy 0.000 claims description 3
- 210000003134 paneth cell Anatomy 0.000 claims description 3
- 102100038778 Amphiregulin Human genes 0.000 claims description 2
- 108010033760 Amphiregulin Proteins 0.000 claims description 2
- 108010016906 Epigen Proteins 0.000 claims description 2
- 102100030323 Epigen Human genes 0.000 claims description 2
- 101800001649 Heparin-binding EGF-like growth factor Proteins 0.000 claims description 2
- 210000004204 blood vessel Anatomy 0.000 claims description 2
- 235000019410 glycyrrhizin Nutrition 0.000 claims description 2
- 230000036737 immune function Effects 0.000 claims description 2
- 230000030214 innervation Effects 0.000 claims description 2
- 102000018710 Heparin-binding EGF-like Growth Factor Human genes 0.000 claims 1
- 102100029837 Probetacellulin Human genes 0.000 claims 1
- 230000004069 differentiation Effects 0.000 abstract description 18
- 210000000813 small intestine Anatomy 0.000 description 59
- 230000011664 signaling Effects 0.000 description 50
- 241000699666 Mus <mouse, genus> Species 0.000 description 48
- 102000045246 noggin Human genes 0.000 description 43
- 108700007229 noggin Proteins 0.000 description 43
- 238000000059 patterning Methods 0.000 description 37
- 238000004458 analytical method Methods 0.000 description 36
- 210000002257 embryonic structure Anatomy 0.000 description 34
- 108020004414 DNA Proteins 0.000 description 33
- 210000001778 pluripotent stem cell Anatomy 0.000 description 30
- 238000010186 staining Methods 0.000 description 28
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 27
- 238000011161 development Methods 0.000 description 26
- 230000018109 developmental process Effects 0.000 description 26
- 210000001035 gastrointestinal tract Anatomy 0.000 description 26
- 101000819074 Homo sapiens Transcription factor GATA-4 Proteins 0.000 description 24
- 102100021380 Transcription factor GATA-4 Human genes 0.000 description 24
- 210000000936 intestine Anatomy 0.000 description 23
- 210000002429 large intestine Anatomy 0.000 description 23
- 241000699670 Mus sp. Species 0.000 description 22
- 210000000981 epithelium Anatomy 0.000 description 22
- 230000001605 fetal effect Effects 0.000 description 21
- 102100031671 Homeobox protein CDX-2 Human genes 0.000 description 20
- 239000003102 growth factor Substances 0.000 description 20
- 102000013814 Wnt Human genes 0.000 description 19
- 108050003627 Wnt Proteins 0.000 description 19
- 239000003550 marker Substances 0.000 description 19
- 230000002441 reversible effect Effects 0.000 description 18
- 238000001727 in vivo Methods 0.000 description 17
- 239000002609 medium Substances 0.000 description 16
- JMIFGARJSWXZSH-UHFFFAOYSA-N DMH1 Chemical compound C1=CC(OC(C)C)=CC=C1C1=CN2N=CC(C=3C4=CC=CC=C4N=CC=3)=C2N=C1 JMIFGARJSWXZSH-UHFFFAOYSA-N 0.000 description 15
- 241000283973 Oryctolagus cuniculus Species 0.000 description 15
- 230000004913 activation Effects 0.000 description 13
- 238000002474 experimental method Methods 0.000 description 13
- 101150003286 gata4 gene Proteins 0.000 description 13
- 238000003559 RNA-seq method Methods 0.000 description 12
- 230000001413 cellular effect Effects 0.000 description 12
- 230000023011 digestive tract development Effects 0.000 description 12
- 210000001161 mammalian embryo Anatomy 0.000 description 12
- 241000283074 Equus asinus Species 0.000 description 11
- 102100030307 Homeobox protein Hox-A13 Human genes 0.000 description 11
- 102100021796 Sonic hedgehog protein Human genes 0.000 description 11
- 108010021685 homeobox protein HOXA13 Proteins 0.000 description 11
- 230000006698 induction Effects 0.000 description 11
- 241000282412 Homo Species 0.000 description 10
- 102100034263 Mucin-2 Human genes 0.000 description 10
- 102100038553 Neurogenin-3 Human genes 0.000 description 10
- 230000008569 process Effects 0.000 description 10
- 108700005087 Homeobox Genes Proteins 0.000 description 9
- 101001133081 Homo sapiens Mucin-2 Proteins 0.000 description 9
- 101000603702 Homo sapiens Neurogenin-3 Proteins 0.000 description 9
- 101000711846 Homo sapiens Transcription factor SOX-9 Proteins 0.000 description 9
- 102100034204 Transcription factor SOX-9 Human genes 0.000 description 9
- 239000005090 green fluorescent protein Substances 0.000 description 9
- 238000011002 quantification Methods 0.000 description 9
- 102100025805 Cadherin-1 Human genes 0.000 description 8
- 108091007854 Cdh1/Fizzy-related Proteins 0.000 description 8
- 230000012010 growth Effects 0.000 description 8
- 230000035800 maturation Effects 0.000 description 8
- VFSUUTYAEQOIMW-YHBQERECSA-N 3-chloro-N-[trans-4-(methylamino)cyclohexyl]-N-[3-(pyridin-4-yl)benzyl]-1-benzothiophene-2-carboxamide Chemical compound C1C[C@@H](NC)CC[C@@H]1N(C(=O)C1=C(C2=CC=CC=C2S1)Cl)CC1=CC=CC(C=2C=CN=CC=2)=C1 VFSUUTYAEQOIMW-YHBQERECSA-N 0.000 description 7
- LVRVABPNVHYXRT-BQWXUCBYSA-N 52906-92-0 Chemical compound C([C@H](N)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(O)=O)C(C)C)C1=CC=CC=C1 LVRVABPNVHYXRT-BQWXUCBYSA-N 0.000 description 7
- 101800001586 Ghrelin Proteins 0.000 description 7
- 102400000442 Ghrelin-28 Human genes 0.000 description 7
- 102100029087 Hepatocyte nuclear factor 6 Human genes 0.000 description 7
- 101000972276 Homo sapiens Mucin-5B Proteins 0.000 description 7
- 102000002419 Motilin Human genes 0.000 description 7
- 101800002372 Motilin Proteins 0.000 description 7
- 102100022494 Mucin-5B Human genes 0.000 description 7
- 108010088847 Peptide YY Proteins 0.000 description 7
- 102100029909 Peptide YY Human genes 0.000 description 7
- 210000001198 duodenum Anatomy 0.000 description 7
- GNKDKYIHGQKHHM-RJKLHVOGSA-N ghrelin Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)CN)COC(=O)CCCCCCC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C1=CC=CC=C1 GNKDKYIHGQKHHM-RJKLHVOGSA-N 0.000 description 7
- 108010082117 matrigel Proteins 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 238000002054 transplantation Methods 0.000 description 7
- YNXLOPYTAAFMTN-SBUIBGKBSA-N C([C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)C1=CC=C(O)C=C1 Chemical compound C([C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)C1=CC=C(O)C=C1 YNXLOPYTAAFMTN-SBUIBGKBSA-N 0.000 description 6
- 101000988619 Homo sapiens Hepatocyte nuclear factor 6 Proteins 0.000 description 6
- 102100040918 Pro-glucagon Human genes 0.000 description 6
- 238000001574 biopsy Methods 0.000 description 6
- 239000002771 cell marker Substances 0.000 description 6
- 210000002969 egg yolk Anatomy 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 230000002496 gastric effect Effects 0.000 description 6
- 210000002438 upper gastrointestinal tract Anatomy 0.000 description 6
- 239000012099 Alexa Fluor family Substances 0.000 description 5
- 241000283707 Capra Species 0.000 description 5
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 description 5
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 5
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 5
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 5
- 102100021088 Homeobox protein Hox-B13 Human genes 0.000 description 5
- 102100040227 Homeobox protein Hox-D13 Human genes 0.000 description 5
- 102100040228 Homeobox protein Hox-D3 Human genes 0.000 description 5
- 101001041145 Homo sapiens Homeobox protein Hox-B13 Proteins 0.000 description 5
- 101001037168 Homo sapiens Homeobox protein Hox-D13 Proteins 0.000 description 5
- 101001037158 Homo sapiens Homeobox protein Hox-D3 Proteins 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- 241000269457 Xenopus tropicalis Species 0.000 description 5
- 229960003722 doxycycline Drugs 0.000 description 5
- XQTWDDCIUJNLTR-CVHRZJFOSA-N doxycycline monohydrate Chemical compound O.O=C1C2=C(O)C=CC=C2[C@H](C)[C@@H]2C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@@H]1[C@H]2O XQTWDDCIUJNLTR-CVHRZJFOSA-N 0.000 description 5
- 210000002919 epithelial cell Anatomy 0.000 description 5
- 210000003405 ileum Anatomy 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 210000001630 jejunum Anatomy 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000002953 phosphate buffered saline Substances 0.000 description 5
- 238000000513 principal component analysis Methods 0.000 description 5
- 102000000905 Cadherin Human genes 0.000 description 4
- 108050007957 Cadherin Proteins 0.000 description 4
- 241001227713 Chiron Species 0.000 description 4
- 102000010792 Chromogranin A Human genes 0.000 description 4
- 108010038447 Chromogranin A Proteins 0.000 description 4
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 4
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 4
- 101150057663 Foxa2 gene Proteins 0.000 description 4
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 4
- 229930182816 L-glutamine Natural products 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 102100038454 Noggin Human genes 0.000 description 4
- 101710183548 Pyridoxal 5'-phosphate synthase subunit PdxS Proteins 0.000 description 4
- 238000000692 Student's t-test Methods 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 108010023082 activin A Proteins 0.000 description 4
- 239000000556 agonist Substances 0.000 description 4
- 230000019552 anatomical structure morphogenesis Effects 0.000 description 4
- 210000002459 blastocyst Anatomy 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 238000010166 immunofluorescence Methods 0.000 description 4
- 210000004347 intestinal mucosa Anatomy 0.000 description 4
- 210000002540 macrophage Anatomy 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 210000003097 mucus Anatomy 0.000 description 4
- 210000000664 rectum Anatomy 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 229960005322 streptomycin Drugs 0.000 description 4
- 238000012353 t test Methods 0.000 description 4
- 230000002103 transcriptional effect Effects 0.000 description 4
- 230000003612 virological effect Effects 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 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
- 241000269350 Anura Species 0.000 description 3
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 3
- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- 206010009900 Colitis ulcerative Diseases 0.000 description 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 3
- QASFUMOKHFSJGL-LAFRSMQTSA-N Cyclopamine Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H](CC2=C3C)[C@@H]1[C@@H]2CC[C@@]13O[C@@H]2C[C@H](C)CN[C@H]2[C@H]1C QASFUMOKHFSJGL-LAFRSMQTSA-N 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 102100040553 FXYD domain-containing ion transport regulator 3 Human genes 0.000 description 3
- 101150033506 HOX gene Proteins 0.000 description 3
- 101000893731 Homo sapiens FXYD domain-containing ion transport regulator 3 Proteins 0.000 description 3
- 101000967222 Homo sapiens Homeobox protein MSX-2 Proteins 0.000 description 3
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 3
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 3
- 102100041030 Pancreas/duodenum homeobox protein 1 Human genes 0.000 description 3
- 241000282376 Panthera tigris Species 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- 108091027967 Small hairpin RNA Proteins 0.000 description 3
- 108020004459 Small interfering RNA Proteins 0.000 description 3
- 201000006704 Ulcerative Colitis Diseases 0.000 description 3
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 3
- 210000001015 abdomen Anatomy 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000031018 biological processes and functions Effects 0.000 description 3
- 229940112869 bone morphogenetic protein Drugs 0.000 description 3
- 210000004534 cecum Anatomy 0.000 description 3
- 230000024245 cell differentiation Effects 0.000 description 3
- 230000001186 cumulative effect Effects 0.000 description 3
- QASFUMOKHFSJGL-UHFFFAOYSA-N cyclopamine Natural products C1C=C2CC(O)CCC2(C)C(CC2=C3C)C1C2CCC13OC2CC(C)CNC2C1C QASFUMOKHFSJGL-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 235000013601 eggs Nutrition 0.000 description 3
- 210000001842 enterocyte Anatomy 0.000 description 3
- 210000002304 esc Anatomy 0.000 description 3
- 238000010195 expression analysis Methods 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 210000004966 intestinal stem cell Anatomy 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 210000003716 mesoderm Anatomy 0.000 description 3
- 230000000877 morphologic effect Effects 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 229920002113 octoxynol Polymers 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 230000002035 prolonged effect Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 230000003248 secreting effect Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 210000001082 somatic cell Anatomy 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000007704 transition Effects 0.000 description 3
- AQQSXKSWTNWXKR-UHFFFAOYSA-N 2-(2-phenylphenanthro[9,10-d]imidazol-3-yl)acetic acid Chemical compound C1(=CC=CC=C1)C1=NC2=C(N1CC(=O)O)C1=CC=CC=C1C=1C=CC=CC=12 AQQSXKSWTNWXKR-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- DDLZLOKCJHBUHD-WAVHTBQISA-N 6-bromoindirubin-3'-oxime Chemical compound O=C/1NC2=CC(Br)=CC=C2C\1=C\1/C(=N/O)/C2=CC=CC=C2N/1 DDLZLOKCJHBUHD-WAVHTBQISA-N 0.000 description 2
- 108010059616 Activins Proteins 0.000 description 2
- 102400001242 Betacellulin Human genes 0.000 description 2
- 102100025423 Bone morphogenetic protein receptor type-1A Human genes 0.000 description 2
- 241000252212 Danio rerio Species 0.000 description 2
- 102100021420 Defensin-5 Human genes 0.000 description 2
- 102100030074 Dickkopf-related protein 1 Human genes 0.000 description 2
- 101710099518 Dickkopf-related protein 1 Proteins 0.000 description 2
- 201000009051 Embryonal Carcinoma Diseases 0.000 description 2
- 102100024802 Fibroblast growth factor 23 Human genes 0.000 description 2
- 229920002527 Glycogen Polymers 0.000 description 2
- 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 101150111172 HOX13 gene Proteins 0.000 description 2
- 102100040615 Homeobox protein MSX-2 Human genes 0.000 description 2
- 101000934638 Homo sapiens Bone morphogenetic protein receptor type-1A Proteins 0.000 description 2
- 101001041589 Homo sapiens Defensin-5 Proteins 0.000 description 2
- 101001051973 Homo sapiens Fibroblast growth factor 23 Proteins 0.000 description 2
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 2
- 101001067833 Homo sapiens Peptidyl-prolyl cis-trans isomerase A Proteins 0.000 description 2
- 102100026818 Inhibin beta E chain Human genes 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 2
- 102100025744 Mothers against decapentaplegic homolog 1 Human genes 0.000 description 2
- 108010063954 Mucins Proteins 0.000 description 2
- 102000015728 Mucins Human genes 0.000 description 2
- 101710096141 Neurogenin-3 Proteins 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- 102100034539 Peptidyl-prolyl cis-trans isomerase A Human genes 0.000 description 2
- 208000037062 Polyps Diseases 0.000 description 2
- 101100247004 Rattus norvegicus Qsox1 gene Proteins 0.000 description 2
- 101700032040 SMAD1 Proteins 0.000 description 2
- 101150106167 SOX9 gene Proteins 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 2
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 239000000488 activin Substances 0.000 description 2
- 239000012574 advanced DMEM Substances 0.000 description 2
- 210000001815 ascending colon Anatomy 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 101150067309 bmp4 gene Proteins 0.000 description 2
- 230000005754 cellular signaling Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 210000004953 colonic tissue Anatomy 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000013020 embryo development Effects 0.000 description 2
- 230000002124 endocrine Effects 0.000 description 2
- 230000001973 epigenetic effect Effects 0.000 description 2
- 238000010353 genetic engineering Methods 0.000 description 2
- 210000001654 germ layer Anatomy 0.000 description 2
- 229940096919 glycogen Drugs 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 238000003125 immunofluorescent labeling Methods 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 238000012744 immunostaining Methods 0.000 description 2
- 238000007901 in situ hybridization Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 238000013507 mapping Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 210000002050 maxilla Anatomy 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 238000002493 microarray Methods 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 230000035479 physiological effects, processes and functions Effects 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000008672 reprogramming Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 230000009131 signaling function Effects 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 210000003014 totipotent stem cell Anatomy 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 210000003384 transverse colon Anatomy 0.000 description 2
- 210000003954 umbilical cord Anatomy 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- 210000002229 urogenital system Anatomy 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- OZFAFGSSMRRTDW-UHFFFAOYSA-N (2,4-dichlorophenyl) benzenesulfonate Chemical compound ClC1=CC(Cl)=CC=C1OS(=O)(=O)C1=CC=CC=C1 OZFAFGSSMRRTDW-UHFFFAOYSA-N 0.000 description 1
- JESCETIFNOFKEU-SJORKVTESA-N (2s,5r)-5-[4-[(2-fluorophenyl)methoxy]phenyl]pyrrolidine-2-carboxamide Chemical compound N1[C@H](C(=O)N)CC[C@@H]1C(C=C1)=CC=C1OCC1=CC=CC=C1F JESCETIFNOFKEU-SJORKVTESA-N 0.000 description 1
- VFSUUTYAEQOIMW-UHFFFAOYSA-N 3-chloro-n-[4-(methylamino)cyclohexyl]-n-[(3-pyridin-4-ylphenyl)methyl]-1-benzothiophene-2-carboxamide Chemical compound C1CC(NC)CCC1N(C(=O)C1=C(C2=CC=CC=C2S1)Cl)CC1=CC=CC(C=2C=CN=CC=2)=C1 VFSUUTYAEQOIMW-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108020005544 Antisense RNA Proteins 0.000 description 1
- 101100394749 Arabidopsis thaliana HSFB2A gene Proteins 0.000 description 1
- 101100457311 Arabidopsis thaliana MIP1B gene Proteins 0.000 description 1
- 238000012935 Averaging Methods 0.000 description 1
- 101100454433 Biomphalaria glabrata BG01 gene Proteins 0.000 description 1
- 102100031102 C-C motif chemokine 4 Human genes 0.000 description 1
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 description 1
- 108700012434 CCL3 Proteins 0.000 description 1
- 101150047126 CCL4 gene Proteins 0.000 description 1
- 102100024152 Cadherin-17 Human genes 0.000 description 1
- 241000252983 Caecum Species 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 101710147336 Choline/ethanolamine kinase Proteins 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- 206010009269 Cleft palate Diseases 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 102000012422 Collagen Type I Human genes 0.000 description 1
- 108010022452 Collagen Type I Proteins 0.000 description 1
- 102100022785 Creatine kinase B-type Human genes 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 101100295776 Drosophila melanogaster onecut gene Proteins 0.000 description 1
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 1
- 108091008794 FGF receptors Proteins 0.000 description 1
- 241000027355 Ferocactus setispinus Species 0.000 description 1
- 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 108090000852 Forkhead Transcription Factors Proteins 0.000 description 1
- 102000004315 Forkhead Transcription Factors Human genes 0.000 description 1
- 102400000921 Gastrin Human genes 0.000 description 1
- 108010052343 Gastrins Proteins 0.000 description 1
- 201000003741 Gastrointestinal carcinoma Diseases 0.000 description 1
- 102100032606 Heat shock factor protein 1 Human genes 0.000 description 1
- 102000003693 Hedgehog Proteins Human genes 0.000 description 1
- 108090000031 Hedgehog Proteins Proteins 0.000 description 1
- 102400001369 Heparin-binding EGF-like growth factor Human genes 0.000 description 1
- 108010086527 Hepatocyte Nuclear Factor 6 Proteins 0.000 description 1
- 102100029284 Hepatocyte nuclear factor 3-beta Human genes 0.000 description 1
- 101150094793 Hes3 gene Proteins 0.000 description 1
- 101150029234 Hes5 gene Proteins 0.000 description 1
- 108091016366 Histone-lysine N-methyltransferase EHMT1 Proteins 0.000 description 1
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 description 1
- 101000762247 Homo sapiens Cadherin-17 Proteins 0.000 description 1
- 101000867525 Homo sapiens Heat shock factor protein 1 Proteins 0.000 description 1
- 101001062347 Homo sapiens Hepatocyte nuclear factor 3-beta Proteins 0.000 description 1
- 101001139130 Homo sapiens Krueppel-like factor 5 Proteins 0.000 description 1
- 101000934372 Homo sapiens Macrosialin Proteins 0.000 description 1
- 101000819088 Homo sapiens Transcription factor GATA-6 Proteins 0.000 description 1
- 101000843556 Homo sapiens Transcription factor HES-1 Proteins 0.000 description 1
- 101000652324 Homo sapiens Transcription factor SOX-17 Proteins 0.000 description 1
- 101000642523 Homo sapiens Transcription factor SOX-7 Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- 102100040487 Keratin, type I cytoskeletal 13 Human genes 0.000 description 1
- 108010065070 Keratin-13 Proteins 0.000 description 1
- 102100020680 Krueppel-like factor 5 Human genes 0.000 description 1
- 101150017554 LGR5 gene Proteins 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- 102100025136 Macrosialin Human genes 0.000 description 1
- 108010008705 Mucin-2 Proteins 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 239000012580 N-2 Supplement Substances 0.000 description 1
- 108010069196 Neural Cell Adhesion Molecules Proteins 0.000 description 1
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 101100230208 Oryza sativa subsp. japonica GSK2 gene Proteins 0.000 description 1
- 101100070550 Oryza sativa subsp. japonica HSFA2C gene Proteins 0.000 description 1
- 238000009004 PCR Kit Methods 0.000 description 1
- 102000000470 PDZ domains Human genes 0.000 description 1
- 108050008994 PDZ domains Proteins 0.000 description 1
- 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 1
- 102000035554 Proglucagon Human genes 0.000 description 1
- 108010058003 Proglucagon Proteins 0.000 description 1
- 108010026552 Proteome Proteins 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 238000010802 RNA extraction kit Methods 0.000 description 1
- 239000013614 RNA sample Substances 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 101100016889 Rattus norvegicus Hes2 gene Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 208000013959 SATB2-associated syndrome Diseases 0.000 description 1
- 102100021382 Transcription factor GATA-6 Human genes 0.000 description 1
- 102100030798 Transcription factor HES-1 Human genes 0.000 description 1
- 102100027654 Transcription factor PU.1 Human genes 0.000 description 1
- 102100030243 Transcription factor SOX-17 Human genes 0.000 description 1
- 102100036730 Transcription factor SOX-7 Human genes 0.000 description 1
- 241000677635 Tuxedo Species 0.000 description 1
- 101150071882 US17 gene Proteins 0.000 description 1
- 102000018070 Uroplakin Ia Human genes 0.000 description 1
- 108010066197 Uroplakin Ia Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 229930003779 Vitamin B12 Natural products 0.000 description 1
- ITBGJNVZJBVPLJ-UHFFFAOYSA-N WAY-316606 Chemical compound FC(F)(F)C1=CC=C(S(=O)(=O)C=2C=CC=CC=2)C=C1S(=O)(=O)NC1CCNCC1 ITBGJNVZJBVPLJ-UHFFFAOYSA-N 0.000 description 1
- 206010047924 Wheezing Diseases 0.000 description 1
- 241000269368 Xenopus laevis Species 0.000 description 1
- 101001062354 Xenopus tropicalis Forkhead box protein A2 Proteins 0.000 description 1
- AXIKDPDWFVPGOD-UHFFFAOYSA-O [7-(dimethylamino)phenothiazin-3-ylidene]-dimethylazanium;2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-10-ium-9-yl)benzoic acid Chemical compound C1=CC(=[N+](C)C)C=C2SC3=CC(N(C)C)=CC=C3N=C21.OC(=O)C1=CC=CC=C1C1=C(C=C(Br)C(O)=C2Br)C2=[O+]C2=C1C=C(Br)C(O)=C2Br AXIKDPDWFVPGOD-UHFFFAOYSA-O 0.000 description 1
- 210000003892 absorptive cell Anatomy 0.000 description 1
- 108010076089 accutase Proteins 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 108010023079 activin B Proteins 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- 238000011316 allogeneic transplantation Methods 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 210000002159 anterior chamber Anatomy 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 239000003613 bile acid Substances 0.000 description 1
- 230000003851 biochemical process Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229940087828 buprenex Drugs 0.000 description 1
- RMRJXGBAOAMLHD-IHFGGWKQSA-N buprenorphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)CN2CC1CC1 RMRJXGBAOAMLHD-IHFGGWKQSA-N 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 230000005907 cancer growth Effects 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000023549 cell-cell signaling Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 210000003850 cellular structure Anatomy 0.000 description 1
- AOXOCDRNSPFDPE-UKEONUMOSA-N chembl413654 Chemical compound C([C@H](C(=O)NCC(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](C)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@@H](N)CCC(O)=O)C1=CC=C(O)C=C1 AOXOCDRNSPFDPE-UKEONUMOSA-N 0.000 description 1
- 210000003837 chick embryo Anatomy 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 208000001134 chromosome 2q32-q33 deletion syndrome Diseases 0.000 description 1
- FDJOLVPMNUYSCM-WZHZPDAFSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+3].N#[C-].N([C@@H]([C@]1(C)[N-]\C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C(\C)/C1=N/C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C\C1=N\C([C@H](C1(C)C)CCC(N)=O)=C/1C)[C@@H]2CC(N)=O)=C\1[C@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]1[C@@H](O)[C@@H](N2C3=CC(C)=C(C)C=C3N=C2)O[C@@H]1CO FDJOLVPMNUYSCM-WZHZPDAFSA-L 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000003184 complementary RNA Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- QTCANKDTWWSCMR-UHFFFAOYSA-N costic aldehyde Natural products C1CCC(=C)C2CC(C(=C)C=O)CCC21C QTCANKDTWWSCMR-UHFFFAOYSA-N 0.000 description 1
- 239000006059 cover glass Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 229960003964 deoxycholic acid Drugs 0.000 description 1
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
- 210000001731 descending colon Anatomy 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 230000024634 digestive tract morphogenesis Effects 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 210000004921 distal colon Anatomy 0.000 description 1
- XHBVYDAKJHETMP-UHFFFAOYSA-N dorsomorphin Chemical compound C=1C=C(C2=CN3N=CC(=C3N=C2)C=2C=CN=CC=2)C=CC=1OCCN1CCCCC1 XHBVYDAKJHETMP-UHFFFAOYSA-N 0.000 description 1
- 238000012137 double-staining Methods 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 210000003981 ectoderm Anatomy 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 210000002308 embryonic cell Anatomy 0.000 description 1
- 231100001129 embryonic lethality Toxicity 0.000 description 1
- 210000003890 endocrine cell Anatomy 0.000 description 1
- 230000020619 endoderm development Effects 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 230000002922 epistatic effect Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 210000004905 finger nail Anatomy 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 210000003953 foreskin Anatomy 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 238000011990 functional testing Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 210000001647 gastrula Anatomy 0.000 description 1
- 230000007045 gastrulation Effects 0.000 description 1
- 238000012239 gene modification Methods 0.000 description 1
- 230000005017 genetic modification Effects 0.000 description 1
- 235000013617 genetically modified food Nutrition 0.000 description 1
- 230000002710 gonadal effect Effects 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000009459 hedgehog signaling Effects 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 238000013427 histology analysis Methods 0.000 description 1
- 102000045896 human BMP2 Human genes 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000012296 in situ hybridization assay Methods 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 201000002313 intestinal cancer Diseases 0.000 description 1
- 230000008978 intestinal localization Effects 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- ISTFUJWTQAMRGA-UHFFFAOYSA-N iso-beta-costal Natural products C1C(C(=C)C=O)CCC2(C)CCCC(C)=C21 ISTFUJWTQAMRGA-UHFFFAOYSA-N 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 230000002197 limbic effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000031142 liver development Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000008567 mammal embryogenesis Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 238000010208 microarray analysis Methods 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 230000003990 molecular pathway Effects 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 210000000472 morula Anatomy 0.000 description 1
- 210000002894 multi-fate stem cell Anatomy 0.000 description 1
- 210000000282 nail Anatomy 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000007472 neurodevelopment Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000014511 neuron projection development Effects 0.000 description 1
- 230000006576 neuronal survival Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 238000012758 nuclear staining Methods 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 235000015816 nutrient absorption Nutrition 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000025342 organ morphogenesis Effects 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000015031 pancreas development Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 210000003200 peritoneal cavity Anatomy 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 108010011110 polyarginine Proteins 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 229940076155 protein modulator Drugs 0.000 description 1
- 108010008929 proto-oncogene protein Spi-1 Proteins 0.000 description 1
- 210000005126 pseudostratified columnar epithelium Anatomy 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 230000008521 reorganization Effects 0.000 description 1
- 210000002955 secretory cell Anatomy 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 108091006024 signal transducing proteins Proteins 0.000 description 1
- 102000034285 signal transducing proteins Human genes 0.000 description 1
- 210000005124 simple cuboidal epithelium Anatomy 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 230000008410 smoothened signaling pathway Effects 0.000 description 1
- TUPFOYXHAYOHIB-YCAIQWGJSA-M sodium;(2s,5r,6r)-6-[[(2r)-2-[(4-ethyl-2,3-dioxopiperazine-1-carbonyl)amino]-2-phenylacetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate;(2s,3s,5r)-3-methyl-4,4,7-trioxo-3-(triazol-1-ylmethyl)-4$l^{6}-thia-1-azabicyclo[3.2.0]h Chemical compound [Na+].C([C@]1(C)S([C@H]2N(C(C2)=O)[C@H]1C(O)=O)(=O)=O)N1C=CN=N1.O=C1C(=O)N(CC)CCN1C(=O)N[C@H](C=1C=CC=CC=1)C(=O)N[C@@H]1C(=O)N2[C@@H](C([O-])=O)C(C)(C)S[C@@H]21 TUPFOYXHAYOHIB-YCAIQWGJSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000000528 statistical test Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229960005404 sulfamethoxazole Drugs 0.000 description 1
- JLKIGFTWXXRPMT-UHFFFAOYSA-N sulphamethoxazole Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1 JLKIGFTWXXRPMT-UHFFFAOYSA-N 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 208000001608 teratocarcinoma Diseases 0.000 description 1
- 235000021195 test diet Nutrition 0.000 description 1
- 108091008023 transcriptional regulators Proteins 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000012250 transgenic expression Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
- IEDVJHCEMCRBQM-UHFFFAOYSA-N trimethoprim Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 IEDVJHCEMCRBQM-UHFFFAOYSA-N 0.000 description 1
- 229960001082 trimethoprim Drugs 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 210000002444 unipotent stem cell Anatomy 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 235000019163 vitamin B12 Nutrition 0.000 description 1
- 239000011715 vitamin B12 Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 210000001325 yolk sac Anatomy 0.000 description 1
- 229940104666 zosyn Drugs 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
- C12N5/0679—Cells of the gastro-intestinal tract
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
- C07K14/485—Epidermal growth factor [EGF], i.e. urogastrone
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
- C07K14/50—Fibroblast growth factor [FGF]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
- C07K14/51—Bone morphogenetic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
-
- 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
- C12N5/0697—Artificial constructs associating cells of different lineages, e.g. tissue equivalents
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5082—Supracellular entities, e.g. tissue, organisms
- G01N33/5088—Supracellular entities, e.g. tissue, organisms of vertebrates
-
- 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
- C12N2501/10—Growth factors
-
- 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
- C12N2501/10—Growth factors
- C12N2501/11—Epidermal growth factor [EGF]
-
- 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
- C12N2501/10—Growth factors
- C12N2501/113—Acidic fibroblast growth factor (aFGF, FGF-1)
-
- 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
- C12N2501/10—Growth factors
- C12N2501/115—Basic fibroblast growth factor (bFGF, FGF-2)
-
- 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
- C12N2501/10—Growth factors
- C12N2501/117—Keratinocyte growth factors (KGF-1, i.e. FGF-7; KGF-2, i.e. FGF-12)
-
- 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
- C12N2501/10—Growth factors
- C12N2501/119—Other fibroblast growth factors, e.g. FGF-4, FGF-8, FGF-10
-
- 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
- C12N2501/10—Growth factors
- C12N2501/155—Bone morphogenic proteins [BMP]; Osteogenins; Osteogenic factor; Bone inducing factor
-
- 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
- C12N2501/10—Growth factors
- C12N2501/16—Activin; Inhibin; Mullerian inhibiting substance
-
- 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
- C12N2501/41—Hedgehog proteins; Cyclopamine (inhibitor)
-
- 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
- C12N2503/00—Use of cells in diagnostics
- C12N2503/02—Drug screening
-
- 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
-
- 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
- C12N2506/45—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from artificially induced pluripotent stem cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2513/00—3D culture
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2533/00—Supports or coatings for cell culture, characterised by material
- C12N2533/90—Substrates of biological origin, e.g. extracellular matrix, decellularised tissue
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Cell Biology (AREA)
- Microbiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- General Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Toxicology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Environmental Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Animal Behavior & Ethology (AREA)
- Animal Husbandry (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020237024207A KR102807995B1 (ko) | 2016-12-05 | 2017-12-05 | 결장 유사장기 및 이를 제조 및 사용하는 방법 |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662429948P | 2016-12-05 | 2016-12-05 | |
| US62/429,948 | 2016-12-05 | ||
| US201762478962P | 2017-03-30 | 2017-03-30 | |
| US62/478,962 | 2017-03-30 | ||
| PCT/US2017/064600 WO2018106628A1 (en) | 2016-12-05 | 2017-12-05 | Colonic organoids and methods of making and using same |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020237024207A Division KR102807995B1 (ko) | 2016-12-05 | 2017-12-05 | 결장 유사장기 및 이를 제조 및 사용하는 방법 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20190088527A KR20190088527A (ko) | 2019-07-26 |
| KR102558606B1 true KR102558606B1 (ko) | 2023-07-26 |
Family
ID=62492104
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020197018724A Active KR102558606B1 (ko) | 2016-12-05 | 2017-12-05 | 결장 유사장기 및 이를 제조 및 사용하는 방법 |
| KR1020257015203A Pending KR20250068799A (ko) | 2016-12-05 | 2017-12-05 | 결장 유사장기 및 이를 제조 및 사용하는 방법 |
| KR1020237024207A Active KR102807995B1 (ko) | 2016-12-05 | 2017-12-05 | 결장 유사장기 및 이를 제조 및 사용하는 방법 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020257015203A Pending KR20250068799A (ko) | 2016-12-05 | 2017-12-05 | 결장 유사장기 및 이를 제조 및 사용하는 방법 |
| KR1020237024207A Active KR102807995B1 (ko) | 2016-12-05 | 2017-12-05 | 결장 유사장기 및 이를 제조 및 사용하는 방법 |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US11767515B2 (https=) |
| EP (1) | EP3548507A4 (https=) |
| JP (3) | JP7068305B2 (https=) |
| KR (3) | KR102558606B1 (https=) |
| CN (2) | CN118909916A (https=) |
| AU (3) | AU2017373767B2 (https=) |
| CA (1) | CA3045145A1 (https=) |
| IL (1) | IL267109A (https=) |
| NZ (1) | NZ753873A (https=) |
| SG (1) | SG10202105768WA (https=) |
| WO (1) | WO2018106628A1 (https=) |
Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9719068B2 (en) | 2010-05-06 | 2017-08-01 | Children's Hospital Medical Center | Methods and systems for converting precursor cells into intestinal tissues through directed differentiation |
| SG10201801654RA (en) | 2014-05-28 | 2018-04-27 | Childrens Hospital Med Ct | Methods and systems for converting precursor cells into gastric tissues through directed differentiation |
| AU2015331848B2 (en) | 2014-10-17 | 2022-03-03 | Children's Hospital Medical Center, D/B/A Cincinnati Children's Hospital Medical Center | In vivo model of human small intestine using pluripotent stem cells and methods of making and using same |
| CN109415685B (zh) | 2016-05-05 | 2023-07-04 | 儿童医院医疗中心 | 用于体外制造胃底组织的方法和与其相关的组合物 |
| EP4553082A3 (en) | 2016-11-04 | 2025-08-20 | Children's Hospital Medical Center | Liver organoid compositions and methods of making and using same |
| EP3548507A4 (en) | 2016-12-05 | 2020-07-15 | Children's Hospital Medical Center | COLON ORGANOIDS AND PROCESSES FOR THE PREPARATION AND USE THEREOF |
| JP7248586B2 (ja) | 2017-04-14 | 2023-03-29 | チルドレンズ ホスピタル メディカル センター | 複数ドナー幹細胞組成物およびそれを作製する方法 |
| EP3625331B1 (en) * | 2017-05-19 | 2024-07-10 | Cedars-Sinai Medical Center | Systems and methods for growth of intestinal cells |
| EP3694603B1 (en) | 2017-10-10 | 2026-04-08 | Children's Hospital Medical Center | Esophageal tissue and/or organoid compositions and methods of making same |
| EP3727394A4 (en) | 2017-12-21 | 2021-09-08 | Children's Hospital Medical Center | DIGITALIZED HUMAN ORGANOIDS AND METHOD OF USING THEREOF |
| EP3787613B1 (en) | 2018-04-30 | 2026-03-11 | Cedars-Sinai Medical Center | Pkc activation for use in treating early onset sporadic parkinson's disease |
| EP4678727A3 (en) | 2018-07-26 | 2026-03-11 | Children's Hospital Medical Center | Hepato-biliary-pancreatic tissues and methods of making same |
| CA3112026A1 (en) * | 2018-09-12 | 2020-03-19 | Children's Hospital Medical Center | Organoid compositions for the production of hematopoietic stem cells and derivatives thereof |
| US12600943B2 (en) | 2019-02-01 | 2026-04-14 | The University Of Hong Kong | Innervated organoid compositions and methods of making same |
| US20220220448A1 (en) * | 2019-05-15 | 2022-07-14 | The Cleveland Clinic Foundation | Induced human colitic organoids |
| AU2020283048A1 (en) | 2019-05-31 | 2021-12-23 | Children's Hospital Medical Center | Shaped organoid compositions and methods of making same |
| US12497597B2 (en) | 2019-05-31 | 2025-12-16 | Children's Hospital Medical Center | Methods of generating and expanding hematopoietic stem cells |
| US20220411747A1 (en) * | 2019-10-31 | 2022-12-29 | University Health Network | Medium and methods for culturing organoids |
| CN111849860B (zh) * | 2020-06-01 | 2021-12-21 | 浙江大学 | 一种利用铁元素调控肠道干细胞分化的方法及应用 |
| WO2022025269A1 (ja) * | 2020-07-30 | 2022-02-03 | 国立研究開発法人理化学研究所 | 膀胱オルガノイド及びその製造方法 |
| CN113009155B (zh) * | 2021-03-05 | 2022-03-25 | 温州医科大学慈溪生物医药研究院 | Fgf20在制备诊断溃疡性结肠炎试剂的应用 |
| IL281561A (en) | 2021-03-16 | 2022-10-01 | Yeda Res & Dev | Methods and devices for ex-utero mouse embryonic development |
| CN113388572B (zh) * | 2021-08-17 | 2021-11-19 | 天九再生医学(天津)科技有限公司 | 高效人多能干细胞体外诱导分化为多谱系小肠类器官方法 |
| EP4388083A4 (en) * | 2021-08-19 | 2025-07-09 | Childrens Hospital Med Ct | VASCULARIZED ORGANOIDS |
| CN114107208A (zh) * | 2021-11-12 | 2022-03-01 | 复旦大学附属中山医院 | 一种人源性类器官库的制备方法 |
| US12435335B2 (en) | 2022-06-06 | 2025-10-07 | Cornell University | Promoting nutrient absorption through the colon |
| KR102843172B1 (ko) * | 2023-01-04 | 2025-08-05 | 연세대학교 산학협력단 | 불일치 복구 유전자 기능 결핍 환자에서 환자 유래 오가노이드를 이용한 개인별 dna 손상 반응 평가 및 암 위험도 예측 |
| WO2024192567A1 (zh) * | 2023-03-17 | 2024-09-26 | 北京大学 | 建立新型人肠道及结直肠肿瘤类器官培养体系 |
| EP4731750A2 (en) | 2023-06-23 | 2026-04-29 | Children's Hospital Medical Center | Methods of matrix-free suspension culture |
| WO2025035155A1 (en) * | 2023-08-10 | 2025-02-13 | The Regents Of The University Of California | Foxo inhibition to augment gastrointestinal function and paneth cell function |
| WO2025072803A1 (en) | 2023-09-29 | 2025-04-03 | Children's Hospital Medical Center | Ntrk2 signaling-mediated alveolar capillary injury and repair |
| CN118501457B (zh) * | 2024-04-29 | 2025-06-17 | 南通大学附属医院 | PPP6R1基因及其RNAi慢病毒干扰系统和应用 |
| CN118240750B (zh) * | 2024-05-28 | 2024-08-13 | 淇嘉科技(苏州)有限公司 | 具有免疫细胞的结肠类器官构建方法 |
| CN118374432B (zh) * | 2024-06-26 | 2024-10-01 | 淇嘉科技(苏州)有限公司 | 匀质化肠道类器官制备方法 |
| CN118374446B (zh) * | 2024-06-26 | 2024-10-01 | 淇嘉科技(苏州)有限公司 | 巨噬细胞包含型结肠类器官批量制备方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012168930A2 (en) * | 2011-06-10 | 2012-12-13 | Koninklijke Nederlandse Akademie Van Wetenschappen (Knaw) | Culture media for stem cells |
| US20130137130A1 (en) * | 2010-05-06 | 2013-05-30 | Children's Hospital Medical Center | Methods and systems for converting precursor cells into intestinal tissues through directed differentiation |
Family Cites Families (311)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU9031591A (en) | 1990-10-29 | 1992-05-26 | Regents Of The University Of Minnesota | A bioartificial liver |
| US5523226A (en) | 1993-05-14 | 1996-06-04 | Biotechnology Research And Development Corp. | Transgenic swine compositions and methods |
| US5912227A (en) | 1995-01-27 | 1999-06-15 | North Carolina State University | Method of enhancing nutrient uptake |
| WO1998021312A1 (en) | 1996-11-08 | 1998-05-22 | Rpms Technology Limited | Human hepatocytes in three-dimensional support systems |
| CA2279996A1 (en) | 1997-01-16 | 1998-07-16 | Yissum Research Development Company Of The Hebrew University In Jerusale M | A device and method for performing a biological modification of a fluid |
| US7291626B1 (en) | 1998-04-09 | 2007-11-06 | John Hopkins University School Of Medicine | Inhibitors of hedgehog signaling pathways, compositions and uses related thereto |
| US20010041964A1 (en) | 1998-09-14 | 2001-11-15 | George M. Grass | Pharmacokinetic-based drug design tool and method |
| US7759113B2 (en) | 1999-04-30 | 2010-07-20 | The General Hospital Corporation | Fabrication of tissue lamina using microfabricated two-dimensional molds |
| US6607501B2 (en) | 2001-05-14 | 2003-08-19 | Reynolds G. Gorsuch | Process and apparatus for utilization of in vivo extracted plasma with tissue engineering devices, bioreactors, artificial organs, and cell therapy applications |
| AU2002367580A1 (en) | 2001-05-16 | 2003-09-22 | Tracy C. Grikscheit | Tissue-engineered organs |
| IL162131A0 (en) | 2001-12-07 | 2005-11-20 | Geron Corp | Islet cells from human embryonic stem cells |
| US20050170506A1 (en) | 2002-01-16 | 2005-08-04 | Primegen Biotech Llc | Therapeutic reprogramming, hybrid stem cells and maturation |
| US20030187515A1 (en) | 2002-03-26 | 2003-10-02 | Hariri Robert J. | Collagen biofabric and methods of preparing and using the collagen biofabric |
| US7160719B2 (en) | 2002-06-07 | 2007-01-09 | Mayo Foundation For Medical Education And Research | Bioartificial liver system |
| WO2004020614A1 (ja) | 2002-08-28 | 2004-03-11 | Asahi Medical Co., Ltd. | 異形断面中空糸膜型細胞含有デバイス |
| TW571101B (en) | 2003-01-21 | 2004-01-11 | Ind Tech Res Inst | Fluid analysis apparatus |
| WO2004071573A2 (en) | 2003-02-07 | 2004-08-26 | The Johns Hopkins University | Hypoxia induced mitogenic factor |
| EP1595867A4 (en) | 2003-02-10 | 2008-05-21 | Banyu Pharma Co Ltd | PIPERIDINE DERIVATIVES AS AN ACTIVE ANTAGONIST AT THE RECIPE OF MELANIN CONCENTRATING HORMONE |
| DE10362002B4 (de) | 2003-06-23 | 2006-10-12 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Adulte pluripotente Stammzellen |
| US7985585B2 (en) | 2004-07-09 | 2011-07-26 | Viacyte, Inc. | Preprimitive streak and mesendoderm cells |
| US7625753B2 (en) | 2003-12-23 | 2009-12-01 | Cythera, Inc. | Expansion of definitive endoderm cells |
| US8586357B2 (en) | 2003-12-23 | 2013-11-19 | Viacyte, Inc. | Markers of definitive endoderm |
| US7541185B2 (en) | 2003-12-23 | 2009-06-02 | Cythera, Inc. | Methods for identifying factors for differentiating definitive endoderm |
| CN103898047B (zh) | 2003-12-23 | 2020-03-03 | 维亚希特公司 | 定形内胚层 |
| US20050266554A1 (en) | 2004-04-27 | 2005-12-01 | D Amour Kevin A | PDX1 expressing endoderm |
| US8647873B2 (en) | 2004-04-27 | 2014-02-11 | Viacyte, Inc. | PDX1 expressing endoderm |
| US8241905B2 (en) | 2004-02-24 | 2012-08-14 | The Curators Of The University Of Missouri | Self-assembling cell aggregates and methods of making engineered tissue using the same |
| DE102004017476B4 (de) | 2004-04-08 | 2009-03-26 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Verfahren zur Herstellung einer Epithelzellen enthaltenden Zellzusammensetzung |
| CN103103158B (zh) | 2004-04-27 | 2016-08-03 | 韦尔赛特公司 | 细胞培养基 |
| JP4650608B2 (ja) | 2004-05-18 | 2011-03-16 | 信越化学工業株式会社 | フォトマスクブランク及びフォトマスクの製造方法 |
| EP1747264B1 (de) | 2004-05-21 | 2012-09-12 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Multizelluläre gewebe- und organkultursysteme |
| US8410246B2 (en) | 2004-06-17 | 2013-04-02 | Thrasos, Inc. | TDF-related compounds and analogs thereof |
| AU2005272078B2 (en) | 2004-07-09 | 2011-04-14 | Viacyte, Inc. | Methods for identifying factors for differentiating definitive endoderm |
| MX2007000510A (es) | 2004-07-12 | 2007-03-29 | Emisphere Tech Inc | Composiciones para suministrar peptido yy y agonistas de pyy. |
| WO2006091231A2 (en) | 2004-07-21 | 2006-08-31 | Ambrx, Inc. | Biosynthetic polypeptides utilizing non-naturally encoded amino acids |
| US8187878B2 (en) | 2004-08-13 | 2012-05-29 | University Of Georgia Research Foundation, Inc. | Methods for increasing definitive endoderm differentiation of pluripotent human embryonic stem cells with PI-3 kinase inhibitors |
| US20060236415A1 (en) | 2005-03-09 | 2006-10-19 | Silversides David W | Neural crest cells specific promoters; isolated neural crest cells; and methods of isolating and of using same |
| US7604929B2 (en) | 2005-04-21 | 2009-10-20 | In Vitro Technologies, Inc. | Cellular compositions and methods for their preparation |
| US8435787B2 (en) | 2005-05-10 | 2013-05-07 | Rutgers, The State University Of New Jersey | Alginate polyelectrolyte encapsulation of embryonic stem cells |
| WO2006126219A1 (en) | 2005-05-26 | 2006-11-30 | Fresenius Medical Care Deutschland G.M.B.H. | Liver progenitor cells |
| GB0517382D0 (en) | 2005-08-26 | 2005-10-05 | Plasticell Ltd | Cell culture |
| WO2007027905A2 (en) | 2005-08-31 | 2007-03-08 | Science And Technology Corporation @ Unm | Human renal stem cells |
| WO2007051038A2 (en) | 2005-10-27 | 2007-05-03 | Cythera, Inc. | Pdx1-expressing dorsal and ventral foregut endoderm |
| US7927869B2 (en) | 2005-11-29 | 2011-04-19 | Spencer Z Rosero | System and method for supporting a biological chip device |
| US20070239083A1 (en) | 2006-01-18 | 2007-10-11 | Axel Voss | Shock wave generators |
| US20070238169A1 (en) | 2006-04-11 | 2007-10-11 | The Board Of Trustees Of The Leland Stanford Junior University | Cell sorter and culture system |
| US8685730B2 (en) | 2006-05-02 | 2014-04-01 | Wisconsin Alumni Research Foundation | Methods and devices for differentiating pluripotent stem cells into cells of the pancreatic lineage |
| WO2007136707A2 (en) | 2006-05-17 | 2007-11-29 | University Of Utah Research Foundation | Methods and compositions related to eosinophil regulation |
| PT2040713E (pt) | 2006-06-27 | 2014-10-13 | Intercept Pharmaceuticals Inc | Para a prevenção ou o tratamento de doenças ou estados clínicos mediados por fxr |
| EP2046266A4 (en) | 2006-07-21 | 2009-11-04 | Massachusetts Inst Technology | ENDMODICIFIED POLY (BETA AMINO ESTER) AND ITS USE |
| US8497240B2 (en) | 2006-08-17 | 2013-07-30 | Amylin Pharmaceuticals, Llc | DPP-IV resistant GIP hybrid polypeptides with selectable properties |
| WO2008075339A2 (en) | 2006-12-18 | 2008-06-26 | Ben Gurion University Of The Negev | Scaffolding for tissue regeneration or repair |
| FR2917425B1 (fr) | 2007-06-18 | 2010-11-19 | Univ Nancy 1 Henri Poincare | Procede de proliferation de cellules sur des multicouches de polyelectrolytes et son application, notamment a la preparation de biomateriaux cellularises |
| GB2467645B (en) | 2007-07-06 | 2011-12-21 | Univ London | A method of proliferating human hepatocyte cells |
| EP2022848A1 (en) | 2007-08-10 | 2009-02-11 | Hubrecht Institut | A method for identifying, expanding, and removing adult stem cells and cancer stem cells |
| WO2009033011A1 (en) * | 2007-09-07 | 2009-03-12 | Children's Hospital Medical Center | Use of secretor, lewis and sialyl antigen levels as predictors for disease |
| US7695963B2 (en) | 2007-09-24 | 2010-04-13 | Cythera, Inc. | Methods for increasing definitive endoderm production |
| EP2235161A1 (en) | 2007-12-11 | 2010-10-06 | Research Development Foundation | Small molecules for neuronal differentiation of embryonic stem cells |
| AU2009203893B2 (en) | 2008-01-08 | 2014-10-02 | The University Of Queensland | Method of producing a population of cells |
| US20110218512A1 (en) | 2008-06-03 | 2011-09-08 | Aethlon Medical, Inc. | Enhanced antiviral therapy methods and devices |
| WO2009146911A2 (en) | 2008-06-04 | 2009-12-10 | Uwe Marx | Organ-on-a-chip-device |
| JP5624981B2 (ja) | 2008-06-24 | 2014-11-12 | ザ・キュレーターズ・オブ・ザ・ユニバーシティ・オブ・ミズーリThe Curators Ofthe University Of Missouri | 自己集合性多細胞体、および前記多細胞体を用いて3次元の生物構造体を作製する方法 |
| ITRM20080342A1 (it) | 2008-06-26 | 2009-12-27 | Univ Degli Studi Udine | Cellule di polpa dentale midollo-simili, metodi per isolamento ed uso. |
| US20130115673A1 (en) | 2008-07-16 | 2013-05-09 | Biotime, Inc. | Methods of Screening Embryonic Progenitor Cell Lines |
| US20110305672A1 (en) | 2008-07-25 | 2011-12-15 | University Of Georgia Research Foundation, Inc. | COMPOSITIONS FOR MESODERM DERIVED ISL1+ MULTIPOTENT CELLS (IMPs), EPICARDIAL PROGENITOR CELLS (EPCs) AND MULTIPOTENT CD56C CELLS (C56Cs) AND METHODS OF PRODUCING AND USING SAME |
| US8895300B2 (en) | 2008-11-04 | 2014-11-25 | Viacyte, Inc. | Scalable primate pluripotent stem cell aggregate suspension culture and differentiation thereof |
| US20110294735A1 (en) | 2008-11-05 | 2011-12-01 | Merck Sharp & Dohme Corp. | Mechanism of neuromedin u action and uses thereof |
| JP5351601B2 (ja) | 2008-12-26 | 2013-11-27 | 矢崎総業株式会社 | 絶縁キャップの製造方法及び絶縁キャップの製造装置 |
| EP2393917B1 (en) | 2009-02-03 | 2016-04-06 | Koninklijke Nederlandse Akademie van Wetenschappen | Culture medium for epithelial stem cells and organoids comprising said stem cells. |
| EP2412800A1 (en) | 2010-07-29 | 2012-02-01 | Koninklijke Nederlandse Akademie van Wetenschappen | Liver organoid, uses thereof and culture method for obtaining them |
| US9752124B2 (en) | 2009-02-03 | 2017-09-05 | Koninklijke Nederlandse Akademie Van Wetenschappen | Culture medium for epithelial stem cells and organoids comprising the stem cells |
| WO2010094694A1 (en) | 2009-02-23 | 2010-08-26 | F. Hoffmann-La Roche Ag | Assays to predict cardiotoxicity |
| CN102421467B (zh) | 2009-03-13 | 2015-04-22 | 梅约医学教育与研究基金会 | 生物人工肝 |
| JP2012520866A (ja) | 2009-03-17 | 2012-09-10 | アプタリス・ファーマ・カナダ・インコーポレイテッド | 高用量のウルソデオキシコール酸で非アルコール性脂肪性肝炎を治療する方法 |
| WO2010127399A1 (en) | 2009-05-06 | 2010-11-11 | Walter And Eliza Hall Institute Of Medical Research | Gene expression profiles and uses thereof |
| WO2014066811A1 (en) | 2012-10-25 | 2014-05-01 | The Johns Hopkins University | Bioreducible poly (b-amino ester)s for sirna delivery |
| CA2762584A1 (en) | 2009-05-20 | 2010-11-25 | Cardio3 Biosciences S.A. | Pharmaceutical composition for the treatment of heart diseases |
| US20120135519A1 (en) | 2009-05-29 | 2012-05-31 | Cellartis Ab | INDUCED DERIVATION OF SPECIFIC ENDODERM FROM hPS CELL-DERIVED DEFINITIVE ENDODERM |
| WO2010143747A1 (ja) | 2009-06-10 | 2010-12-16 | 公立大学法人奈良県立医科大学 | 人工腸管の作製法 |
| WO2010149597A2 (en) | 2009-06-18 | 2010-12-29 | Cellartis Ab | 3D CULTURING SYSTEMS FOR GROWTH AND DIFFERENTIATION OF HUMAN PLURIPOTENT STEM (hPS) CELLS |
| CN105796601A (zh) | 2009-07-16 | 2016-07-27 | 生物时代股份有限公司 | 用于体外和体内软骨发生的方法和组合物 |
| US8926561B2 (en) | 2009-07-30 | 2015-01-06 | Tandem Diabetes Care, Inc. | Infusion pump system with disposable cartridge having pressure venting and pressure feedback |
| US8501476B2 (en) | 2009-10-07 | 2013-08-06 | Brown University | Assays and methods for fusing cell aggregates to form proto-tissues |
| CN101696396A (zh) | 2009-10-27 | 2010-04-21 | 中国人民解放军军事医学科学院卫生学环境医学研究所 | 乙型肝炎病毒体外感染模型的构建方法及应用 |
| CN102740888B (zh) | 2009-11-24 | 2016-10-12 | 奥尔德生物制药公司 | Il-6抗体及其用途 |
| WO2011064309A1 (en) | 2009-11-25 | 2011-06-03 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Method for hepatic differentiation of definitive endoderm cells |
| CN102712902B (zh) | 2009-12-23 | 2019-01-08 | 詹森生物科技公司 | 人胚胎干细胞的分化 |
| US20110231942A1 (en) | 2010-03-17 | 2011-09-22 | Xi He | Tiki1 and tiki2, wnt inhibitors |
| US9394522B2 (en) | 2010-03-22 | 2016-07-19 | Takara Bio Europe Ab | Directed differentiation and maturation of pluripotent cells into hepatocyte like cells by modulation of Wnt-signalling pathway |
| EP2380920A1 (en) | 2010-04-22 | 2011-10-26 | QGel SA | Hydrogel precursor formulation and production process thereof |
| EP2563908B1 (en) | 2010-04-25 | 2019-01-09 | Icahn School of Medicine at Mount Sinai | Generation of anterior foregut endoderm from pluripotent cells |
| WO2011159684A2 (en) | 2010-06-15 | 2011-12-22 | Cellular Dynamics International, Inc. | Generation of induced pluripotent stem cells from small volumes of peripheral blood |
| EP2609191B1 (en) | 2010-08-24 | 2017-11-22 | Regents Of The University Of Minnesota | Non-static suspension culture of cell aggregates |
| CN103154237B (zh) | 2010-08-31 | 2016-03-16 | 詹森生物科技公司 | 多能干细胞的分化 |
| WO2012068170A2 (en) | 2010-11-15 | 2012-05-24 | Jau-Nan Lee | Generation of neural stem cells from human trophoblast stem cells |
| EP2658965B1 (en) | 2010-12-31 | 2016-03-02 | Universität für Bodenkultur Wien | Method of generating induced pluripotent stem cells and differentiated cells |
| US8951781B2 (en) | 2011-01-10 | 2015-02-10 | Illumina, Inc. | Systems, methods, and apparatuses to image a sample for biological or chemical analysis |
| US9200258B2 (en) | 2011-01-27 | 2015-12-01 | University Of Maryland, Baltimore | Multicellular organotypic model of human intestinal mucosa |
| EP2484750A1 (en) | 2011-02-07 | 2012-08-08 | Ecole Polytechnique Fédérale de Lausanne (EPFL) | Monitoring system for cell culture |
| DK2681306T3 (en) | 2011-02-28 | 2019-04-23 | Harvard College | CELL CULTURE SYSTEM |
| GB201106395D0 (en) | 2011-04-14 | 2011-06-01 | Hubrecht Inst | Compounds |
| US20140158233A1 (en) | 2011-05-09 | 2014-06-12 | President And Fellows Of Harvard College | Aerosol delivery to a microfluidic device |
| US10260039B2 (en) | 2011-05-11 | 2019-04-16 | Massachusetts Institute Of Technology | Microgels and microtissues for use in tissue engineering |
| AU2012262139B2 (en) | 2011-06-02 | 2017-02-23 | Children's Medical Center Corporation | Methods and uses for ex vivo tissue culture systems |
| CA2840192A1 (en) | 2011-06-23 | 2012-12-27 | The Children's Hospital Of Philadelphia | Self-renewing endodermal progenitor lines generated from human pluripotent stem cells and methods of use thereof |
| EP2755599B1 (en) | 2011-09-12 | 2020-04-01 | Organovo, Inc. | Platform for engineered implantable tissues and organs and methods of making the same |
| JP2013066414A (ja) | 2011-09-22 | 2013-04-18 | National Institute Of Advanced Industrial Science & Technology | 胃前駆細胞の表面マーカー |
| WO2013063588A1 (en) | 2011-10-28 | 2013-05-02 | The Board Of Trustees Of The Leland Stanford Junior University | Ex vivo culture, proliferation and expansion of primary tissue organoids |
| ES2689265T3 (es) | 2011-11-04 | 2018-11-12 | Inregen | Cribado de fármacos y ensayos de potencia |
| EP2788476B1 (en) | 2011-12-08 | 2019-05-22 | Fred Hutchinson Cancer Research Center | Compositions and methods for enhanced generation of hematopoietic stem/progenitor cells |
| US9725687B2 (en) | 2011-12-09 | 2017-08-08 | President And Fellows Of Harvard College | Integrated human organ-on-chip microphysiological systems |
| US10087422B2 (en) | 2011-12-09 | 2018-10-02 | President And Fellows Of Harvard College | Organ chips and uses thereof |
| US10006904B2 (en) | 2011-12-19 | 2018-06-26 | Umc Utrecht Holding B.V. | Rapid quantitative assay to measure CFTR function in a primary intestinal culture model |
| CN113699105A (zh) | 2011-12-23 | 2021-11-26 | 人类起源公司 | 包含脱细胞并再群体化的胎盘血管支架的类器官 |
| US9828583B2 (en) | 2012-01-13 | 2017-11-28 | The General Hospital Corporation | Isolated human lung progenitor cells and uses thereof |
| US9675646B2 (en) | 2012-01-31 | 2017-06-13 | Wake Forest University Health Sciences | Tubular bioengineered smooth muscle structures |
| AU2013222188A1 (en) | 2012-02-22 | 2014-09-11 | Amgen Inc. | Autologous mammalian models derived from induced pluripotent stem cells and related methods |
| EP2634251A1 (en) | 2012-02-29 | 2013-09-04 | Technische Universität Berlin | 3D in vitro bi-phasic cartilage-bone construct |
| KR20150013471A (ko) | 2012-04-09 | 2015-02-05 | 토마스 제이. 굿윈 | 교류 이온 자기 공명(aimr) 멀티-챔버-배양 장치 및 사용 방법 |
| KR20160027219A (ko) | 2012-05-23 | 2016-03-09 | 에프. 호프만-라 로슈 아게 | 내배엽 및 간세포를 수득하고 사용하는 조성물 및 방법 |
| US20140099709A1 (en) | 2012-06-19 | 2014-04-10 | Organovo, Inc. | Engineered three-dimensional connective tissue constructs and methods of making the same |
| NZ734451A (en) | 2012-06-19 | 2018-12-21 | Intercept Pharmaceuticals Inc | Preparation, uses and solid forms of obeticholic acid |
| DE102012105540A1 (de) | 2012-06-26 | 2014-04-24 | Karlsruher Institut für Technologie | Gefäßmodell, Verfahren zu seiner Herstellung und seine Verwendung |
| WO2014013334A2 (en) | 2012-07-20 | 2014-01-23 | Agency For Science, Technology And Research | In vitro assay for predicting renal proximal tubular cell toxicity |
| US9988606B2 (en) | 2012-07-24 | 2018-06-05 | The Trustees Of Columbia University In The City Of New York | Generation of airway and lung progenitors and epithelial cells and three-dimensional anterior foregut spheres |
| GB201216796D0 (en) | 2012-09-20 | 2012-11-07 | Cambridge Entpr Ltd | In vitro pancreatic differentiation |
| DK2712918T3 (en) | 2012-09-28 | 2015-02-16 | Tissuse Gmbh | Multi-organ-chip with improved lifetime and homeostasis |
| EP2716298A1 (en) | 2012-10-03 | 2014-04-09 | Institut Pasteur | A nod2-dependant pathway of cytoprotection of stem cells |
| US20150329821A1 (en) * | 2012-10-19 | 2015-11-19 | Agency For Science, Technology And Research | Methods of differentiating stem cells into one or more cell lineages |
| EP2735326B1 (en) | 2012-11-26 | 2017-03-08 | Gambro Lundia AB | Liver support system |
| WO2014082096A1 (en) | 2012-11-26 | 2014-05-30 | The Trustees Of Columbia University In The City Of New York | Method for culture of human and mouse prostate organoids and uses thereof |
| EP3031921B1 (en) | 2012-12-12 | 2025-03-12 | The Broad Institute, Inc. | Delivery, engineering and optimization of systems, methods and compositions for sequence manipulation and therapeutic applications |
| EP2743345A1 (en) | 2012-12-13 | 2014-06-18 | IMBA-Institut für Molekulare Biotechnologie GmbH | Three dimensional heterogeneously differentiated tissue culture |
| US20150359849A1 (en) | 2013-01-31 | 2015-12-17 | President And Fellows Of Harvard College | Methods of increasing neuronal connectivity and/or treating a neurodegenerative condition |
| WO2014127170A1 (en) | 2013-02-13 | 2014-08-21 | Wake Forest University Health Sciences | Bioengineered liver constructs and methods relating thereto |
| GB201304245D0 (en) | 2013-03-08 | 2013-04-24 | Inst Quimic De Sarria | Chemical compounds |
| WO2014165056A1 (en) | 2013-03-12 | 2014-10-09 | Board Of Regents, The University Of Texas System | High throughput mechanical strain generating system for cell cultures and applications thereof |
| HUE043785T2 (hu) | 2013-03-13 | 2019-09-30 | Wisconsin Alumni Res Found | Módszerek és anyagok humán pluripotens õssejtek hematoendothelialis differenciálására meghatározott körülmények között |
| US8859286B2 (en) | 2013-03-14 | 2014-10-14 | Viacyte, Inc. | In vitro differentiation of pluripotent stem cells to pancreatic endoderm cells (PEC) and endocrine cells |
| WO2014152906A2 (en) | 2013-03-14 | 2014-09-25 | Research Institute At Nationwide Children's Hospital, Inc. | Tissue engineered intestine |
| CA2899507A1 (en) | 2013-03-14 | 2014-09-25 | The Regents Of The University Of California | In vitro production of medial ganglionic eminence precursor cells |
| PL2970890T3 (pl) | 2013-03-14 | 2020-11-16 | The Brigham And Women's Hospital, Inc. | Kompozycje i sposoby ekspansji i hodowli nabłonkowych komórek macierzystych |
| US9442105B2 (en) | 2013-03-15 | 2016-09-13 | Organovo, Inc. | Engineered liver tissues, arrays thereof, and methods of making the same |
| US20160237400A1 (en) | 2013-03-15 | 2016-08-18 | The Jackson Laboratory | Isolation of non-embryonic stem cells and uses thereof |
| WO2014153294A1 (en) | 2013-03-17 | 2014-09-25 | The Regents Of The University Of California | Method to expand and transduce cultured human small and large intestinal stem cells |
| US9677085B2 (en) | 2013-03-18 | 2017-06-13 | Massachusetts Institute Of Technology | Engineering a heterogeneous tissue from pluripotent stem cells |
| EP2796873A1 (en) | 2013-04-25 | 2014-10-29 | QGel SA | Method for a cell-based drug screening assay and the use thereof |
| US20160245653A1 (en) | 2013-04-30 | 2016-08-25 | Sangtae Park | Cylindrical resonator gyroscope |
| JP6490669B2 (ja) | 2013-05-08 | 2019-03-27 | インリージェン | 単離腎細胞を含有するオルガノイド及びその使用 |
| US10545133B2 (en) | 2013-05-13 | 2020-01-28 | The Johns Hopkins University | Molecular signatures of invasive cancer subpopulations |
| WO2014197622A2 (en) | 2013-06-04 | 2014-12-11 | The Regents Of The University Of California | Liver-mimetic device and method for simulation of hepatic function using such device |
| JP6253265B2 (ja) | 2013-06-05 | 2017-12-27 | 学校法人関西医科大学 | 食道上皮幹細胞の単離方法 |
| AU2014279568B2 (en) | 2013-06-10 | 2020-03-12 | Corning Incorporated | Tissue structure and manufacturing method therefor |
| RU2016100232A (ru) | 2013-06-14 | 2017-07-17 | Дзе Юниверсити Оф Квинсленд | Почечные клетки-предшественники |
| BR112016000706B1 (pt) | 2013-07-23 | 2022-08-16 | Public University Corporation Yokohama City University | Método de integração de um tecido biológico com um sistema vascular in vitro, tecido biológico, método de avaliação de um fármaco, e composição |
| AU2014305843B2 (en) | 2013-08-09 | 2019-08-29 | Ardelyx, Inc. | Compounds and methods for inhibiting phosphate transport |
| ES2764408T3 (es) | 2013-08-28 | 2020-06-03 | Promethera Biosciences S A / N V | Procedimiento para la producción de células progenitoras hepáticas adultas |
| GB201317869D0 (en) | 2013-10-09 | 2013-11-20 | Cambridge Entpr Ltd | In vitro production of foregut stem cells |
| EP3060650A4 (en) | 2013-10-25 | 2017-04-19 | Agency For Science, Technology And Research | Culturing pluripotent stem cells |
| EP3071686B1 (en) | 2013-11-22 | 2020-07-22 | Cellectis SA | Method for generating batches of allogeneic t-cells with averaged potency |
| ES2732730T3 (es) | 2013-11-22 | 2019-11-25 | Riken | Método para producir telencéfalo o tejido progenitor del mismo |
| EP2876441B1 (en) | 2013-11-26 | 2017-10-25 | Bergen Teknologioverforing AS | Quantitative analysis of contact-depending cell-to-cell transfer and disease transmission |
| EP3574985A1 (en) | 2013-12-20 | 2019-12-04 | President And Fellows Of Harvard College | Organomimetic devices and methods of use and manufacturing thereof |
| KR102611973B1 (ko) | 2014-01-14 | 2023-12-08 | 예일 유니버시티 | 기도 세포의 제조를 위한 조성물 및 방법 |
| US11648335B2 (en) | 2014-01-31 | 2023-05-16 | Wake Forest University Health Sciences | Organ/tissue decellularization, framework maintenance and recellularization |
| EA201691607A1 (ru) | 2014-02-11 | 2017-01-30 | Антродженезис Корпорейшн | Микроорганоиды и способы их получения и применения |
| US10369254B2 (en) | 2014-02-26 | 2019-08-06 | The Regents Of The University Of California | Method and apparatus for in vitro kidney organogenesis |
| CN106062181A (zh) | 2014-02-27 | 2016-10-26 | 公立大学法人横滨市立大学 | 自发组织用细胞集合体的制作方法 |
| DE102014003465A1 (de) | 2014-03-11 | 2015-09-17 | NeuroProof GmbH | Gewinnung von Gehirnregion-spezifischen neuronalen Kulturen aus dreidimensionalen Gewebekulturen von Stammzellen |
| US11066649B2 (en) | 2014-03-19 | 2021-07-20 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Method for inducing human cholangiocyte differentiation |
| EP3119401A4 (en) | 2014-03-21 | 2017-12-13 | Tobira Therapeutics, Inc. | Cenicriviroc for the treatment of fibrosis |
| EP3808838B1 (en) | 2014-04-04 | 2024-04-10 | Organovo, Inc. | Engineered three-dimensional breast tissue, adipose tissue, and tumor disease model |
| US10222370B2 (en) | 2014-04-07 | 2019-03-05 | Rush University Medical Center | Screening assay for choice of prebiotic to prevent/treat gastrointestinal and systemic diseases |
| WO2015156929A1 (en) | 2014-04-07 | 2015-10-15 | The Trustees Of Columbia University In The City Of New York | Method for culture of human bladder cell lines and organoids and uses thereof |
| KR102374499B1 (ko) | 2014-04-11 | 2022-03-14 | 사이머베이 쎄라퓨틱스, 인코퍼레이티드 | Nafld 및 nash 의 치료 |
| MX388202B (es) | 2014-04-27 | 2025-03-19 | Univ New York State Res Found | Métodos para generar productos de esmalte in vitro. |
| CA2949171A1 (en) | 2014-05-16 | 2015-11-19 | Koninklijke Nederlandse Akademie Van Wetenschappen | Improved culture method for organoids |
| SG10201801654RA (en) | 2014-05-28 | 2018-04-27 | Childrens Hospital Med Ct | Methods and systems for converting precursor cells into gastric tissues through directed differentiation |
| CN106536707B (zh) | 2014-05-29 | 2018-12-25 | 西奈山伊坎医学院 | 在生物反应器系统中制造心脏类器官的方法和装置 |
| US10426757B2 (en) | 2014-05-29 | 2019-10-01 | Whitehead Institute For Biomedical Research | Compositions and methods for promoting intestinal stem cell and/or non-stem progenitor cell function |
| EP3786285A1 (en) | 2014-06-05 | 2021-03-03 | Cedars-Sinai Medical Center | A novel and efficient method for reprogramming immortalized lymphoblastoid cell lines to induced pluripotent stem cells |
| EP3152296B1 (en) | 2014-06-06 | 2021-08-04 | Vrije Universiteit Brussel | Human hepatic 3d co-culture model and uses thereof |
| EP3158056B1 (en) | 2014-06-20 | 2021-10-06 | Rutgers, the State University of New Jersey | Single cell-derived organoids |
| US10487314B2 (en) | 2014-06-26 | 2019-11-26 | The Trustees Of Columbia University In The City Of New York | Inhibition of serotonin expression in gut enteroendocrine cells results in conversion to insulin-positive cells |
| KR20170063519A (ko) | 2014-07-17 | 2017-06-08 | 셀매틱스, 인크. | 불임 및 관련 병리상태를 평가하기 위한 방법 및 시스템 |
| IL282156B (en) | 2014-07-29 | 2022-07-01 | Shenzhen Hightide Biopharmaceutical Ltd | Berberine salts, ursodeoxycholic salts and combinations, methods of preparation and application thereof |
| US12247224B2 (en) | 2014-07-30 | 2025-03-11 | Senthil Muthuswamy | Organoids for drug screening and personalized medicine |
| SG11201701398SA (en) | 2014-08-22 | 2017-03-30 | Cambridge Entpr Ltd | Resetting pluripotent stem cells |
| KR102101060B1 (ko) | 2014-08-28 | 2020-04-16 | 프로메테라 바이오사이언시즈 에스.에이./엔.브이. | 성체 간 전구 세포의 제조 방법 |
| US20160060707A1 (en) | 2014-08-29 | 2016-03-03 | Immunomedics, Inc. | Identification of Cancer Genes by In-Vivo Fusion of Human Cancer Cells and Animal Cells |
| EP3777863A1 (en) | 2014-09-12 | 2021-02-17 | Tobira Therapeutics, Inc. | Cenicriviroc combination therapy for the treatment of fibrosis |
| KR20170064547A (ko) | 2014-10-06 | 2017-06-09 | 오가노보, 인크. | 조작된 신장 조직, 이의 어레이, 및 이를 제조하는 방법 |
| US20170304369A1 (en) | 2014-10-08 | 2017-10-26 | Agency For Science, Technology And Research | Methods of differentiating stem cells into liver cell lineages |
| EP3207122B1 (en) | 2014-10-14 | 2019-05-08 | FUJIFILM Cellular Dynamics, Inc. | Generation of keratinocytes from pluripotent stem cells and maintenance of keratinocyte cultures |
| AU2015331848B2 (en) | 2014-10-17 | 2022-03-03 | Children's Hospital Medical Center, D/B/A Cincinnati Children's Hospital Medical Center | In vivo model of human small intestine using pluripotent stem cells and methods of making and using same |
| US20160121023A1 (en) | 2014-10-30 | 2016-05-05 | Massachusetts Institute Of Technology | Materials and Methods for Rescue of Ischemic Tissue and Regeneration of Tissue Integrity During Resection, Engraftment and Transplantation |
| WO2016073989A2 (en) | 2014-11-07 | 2016-05-12 | The Trustees Of Columbia University In The City Of New York | Osteochondroreticular stem cells for bone and cartilage regeneration |
| WO2016085765A1 (en) | 2014-11-25 | 2016-06-02 | President And Fellows Of Harvard College | Methods for generation of podocytes from pluripotent stem cells and cells produced by the same |
| US20170260501A1 (en) | 2014-11-25 | 2017-09-14 | International Stem Cell Corporation | Derivation of neural crest stem cells and uses thereof |
| GB201421092D0 (en) | 2014-11-27 | 2015-01-14 | Koninklijke Nederlandse Akademie Van Wetenschappen | Culture medium |
| GB201421094D0 (en) | 2014-11-27 | 2015-01-14 | Koninklijke Nederlandse Akademie Van Wetenschappen | Culture medium |
| AU2014277667B2 (en) | 2014-12-15 | 2022-07-14 | The University Of Queensland | Differentiation of pluripotent stem cells to form renal organoids |
| JP7089240B2 (ja) | 2014-12-22 | 2022-06-22 | エコール・ポリテクニーク・フェデラル・ドゥ・ローザンヌ (ウ・ペ・エフ・エル) | 高い収集能力で哺乳動物細胞を操作(マニピュレーション)する装置 |
| WO2016103269A1 (en) | 2014-12-23 | 2016-06-30 | Ramot At Tel-Aviv University Ltd. | Populations of neural progenitor cells and methods of producing and using same |
| EA201791258A1 (ru) | 2015-01-09 | 2017-12-29 | Джилид Аполло, Ллс | Комбинированная терапия с применением ингибитора ацетил-коа-карбоксилазы (acc) для лечения неалкогольной жировой болезни печени |
| JP6281850B2 (ja) | 2015-01-28 | 2018-02-21 | 公立大学法人横浜市立大学 | 骨髄細胞凝集体の作製方法 |
| US20160256672A1 (en) | 2015-02-10 | 2016-09-08 | Cedars-Sinai Medical Center | Induced pluripotent stem cell-derived hepatocyte based bioartificial liver device |
| CN105985395A (zh) | 2015-02-13 | 2016-10-05 | 江苏奥赛康药业股份有限公司 | 一种奥贝胆酸化合物及含有该化合物的药物组合物 |
| WO2016140716A1 (en) | 2015-03-02 | 2016-09-09 | The Trustees Of Columbia University In The City Of New York | Injectable microtissue systems, devices, and methods |
| CN107427537A (zh) | 2015-03-03 | 2017-12-01 | 哈佛学院院长及董事 | 产生功能性人体组织的方法 |
| US20160257937A1 (en) | 2015-03-06 | 2016-09-08 | University Of North Carolina At Chapel Hill | HUMAN FIBROLAMELLAR HEPATOCELLULAR CARCINOMAS (hFL-HCCS) |
| JP6800875B2 (ja) | 2015-03-06 | 2020-12-16 | マイクロマス ユーケー リミテッド | 急速蒸発イオン化質量分析(「reims」)装置に連結されたイオンアナライザのための流入器具 |
| EA201791982A1 (ru) | 2015-03-09 | 2020-02-17 | Интекрин Терапьютикс, Инк. | Способы лечения неалкогольной жировой болезни печени и/или липодистрофии |
| US10023922B2 (en) | 2015-03-23 | 2018-07-17 | Whitehead Institute For Biomedical Research | Reporter of genomic methylation and uses thereof |
| CR20170456A (es) | 2015-04-07 | 2018-06-13 | Intercept Pharmaceuticals Inc | Composiciones farmacéuticas para terapias combinadas |
| US10087417B2 (en) | 2015-04-22 | 2018-10-02 | William J. Freed | Three-dimensional model of human cortex |
| US10557124B2 (en) | 2015-04-22 | 2020-02-11 | The Regents Of The University Of Michigan | Compositions and methods for obtaining stem cell derived lung tissue, and related uses thereof |
| CN104877964A (zh) | 2015-04-24 | 2015-09-02 | 赵振民 | 一种唾液腺类器官和类腺泡的体外构建方法 |
| PE20180690A1 (es) | 2015-04-27 | 2018-04-23 | Intercept Pharmaceuticals Inc | Composiciones de acido obeticolico y metodos de uso |
| WO2016174604A1 (en) | 2015-04-30 | 2016-11-03 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) | Means and methods for generation of breast stem cells |
| US11299714B2 (en) | 2015-05-11 | 2022-04-12 | The Trustees Of Columbia University In The City Of New York | Engineered adult-like human heart tissue |
| EP3303566B1 (en) | 2015-06-03 | 2020-10-14 | Takara Bio Europe AB | Maturation of mammalian hepatocytes |
| GB201510950D0 (en) | 2015-06-22 | 2015-08-05 | Cambridge Entpr Ltd | In vitro Production of Cholangiocytes |
| WO2016210313A1 (en) | 2015-06-24 | 2016-12-29 | Whitehead Institute For Biomedical Research | Culture medium for generating microglia from pluripotent stem cells and related methods |
| US20180171302A1 (en) | 2015-06-26 | 2018-06-21 | Domenico ACCILI | Genetically Modified IPS Cells That Carry a Marker to Report Expression of Neurogenin3, TPH2, FOXO1 and/or Insulin Genes |
| WO2017009263A1 (en) | 2015-07-10 | 2017-01-19 | Etablissement Francais Du Sang | Method for obtaining human brown/beige adipocytes |
| US10449221B2 (en) | 2015-07-29 | 2019-10-22 | Trustees Of Boston University | Differentiation of stem cells into thyroid tissue |
| WO2017036533A1 (en) | 2015-09-03 | 2017-03-09 | Ecole Polytechnique Federale De Lausanne (Epfl) | Three-dimensional hydrogels for culturing adult epithelial stem cells and organoids |
| AU2016318114B2 (en) | 2015-09-03 | 2023-04-20 | The Brigham And Women's Hospital, Inc. | Three-dimensional differentiation of epiblast spheroids to kidney organoids models stage-specific epithelial physiology, morphogenesis, and disease |
| EP3350313B1 (en) | 2015-09-15 | 2025-11-26 | Agency For Science, Technology And Research (A*star) | Derivation of liver organoids from human pluripotent stem cells |
| JP2018532720A (ja) | 2015-09-16 | 2018-11-08 | トビラ セラピューティクス, インコーポレイテッド | 線維症の治療のためのセニクリビロック併用療法 |
| US20180258404A1 (en) | 2015-09-17 | 2018-09-13 | The Brigham And Women's Hospital, Inc. | Methods of generating nephrons from human pluripotent stem cells |
| US20180273904A1 (en) | 2015-10-02 | 2018-09-27 | Wake Forest University Health Sciences | Spontaneously beating cardiac organoid constructs and integrated body-on-chip apparatus containing the same |
| LU92845B1 (en) | 2015-10-08 | 2017-05-02 | Univ Du Luxembourg Campus Belval | Means and methods for generating midbrain organoids |
| WO2017070007A2 (en) | 2015-10-15 | 2017-04-27 | Wake Forest University Health Sciences | Methods of producing in vitro liver constructs and uses thereof |
| US10993433B2 (en) | 2015-10-15 | 2021-05-04 | Wake Forest University Health Sciences | Method of producing in vitro testicular constructs and uses thereof |
| EP3362554B1 (en) | 2015-10-16 | 2025-09-03 | Wake Forest University Health Sciences | Multi-layer airway organoids and methods of making and using the same |
| WO2017066659A1 (en) | 2015-10-16 | 2017-04-20 | The Trustees Of Columbia University In The City Of New York | Jag1 expression predicts therapeutic response in nash |
| KR102410389B1 (ko) | 2015-10-19 | 2022-06-16 | 에뮬레이트, 인크. | 혈액 뇌 장벽의 미세유체 모델 |
| US12209253B2 (en) | 2016-08-29 | 2025-01-28 | EMULATE, Inc. | Development of spinal cord on a microfluidic chip |
| US10947502B2 (en) | 2015-10-20 | 2021-03-16 | FUJIFILM Cellular Dynamics, Inc. | Methods for directed differentiation of pluripotent stem cells to immune cells |
| SG11201803061UA (en) | 2015-10-21 | 2018-05-30 | Univ Indiana Res & Tech Corp | Methods of generating human inner ear sensory epithelia and sensory neurons |
| SG11201803043VA (en) | 2015-10-21 | 2018-05-30 | Univ Indiana Res & Tech Corp | Derivation of human skin organoids from pluripotent stem cells |
| SG11201803419PA (en) | 2015-10-30 | 2018-05-30 | The Regents Of The Universtiy Of California | Methods of generating t-cells from stem cells and immunotherapeutic methods using the t-cells |
| US11866409B2 (en) | 2015-11-02 | 2024-01-09 | Carmel-Haifa University Economic Corporation Ltd. | Apoptosis related protein in the tgf-beta signaling pathway (ARTS) mimetic compounds, compositions, methods and uses thereof in induction of differentiation and/or apoptosis of premalignant and malignant cells, thereby restoring their normal-like phenotype |
| WO2017079632A1 (en) | 2015-11-04 | 2017-05-11 | Cedars-Sinai Medical Center | Patient-derived ctc-xenograft models |
| HK1257929A1 (zh) | 2015-11-06 | 2019-11-01 | Gemphire Therapeutics Inc. | 治疗混合性血脂异常 |
| KR102932021B1 (ko) | 2015-11-12 | 2026-02-27 | 바이오스테이지, 인크. | 문합 또는 다른 생리학적 위치에서 위장 조직을 생성하기 위한 시스템 및 방법 |
| WO2017083705A1 (en) | 2015-11-13 | 2017-05-18 | The Johns Hopkins University | Cell culture system and method of use thereof |
| EP3383996B1 (en) | 2015-12-04 | 2024-10-16 | President and Fellows of Harvard College | Devices for simulating a function of a liver tissue and methods of use and manufacturing thereof |
| EP3414322A4 (en) | 2015-12-23 | 2020-03-04 | Memorial Sloan-Kettering Cancer Center | CELL THERAPY AND DRUG DISCOVERY BASED ON CELL LINES DERIVED FROM HUMAN ENTERAL NEURAL CREST DERIVED FROM PLURIPOTENT STEM CELLS |
| KR101733137B1 (ko) | 2015-12-30 | 2017-05-08 | (주)엑셀세라퓨틱스 | 연골조직 제조를 위한 3차원 오가노이드 블록 제작 방법 |
| EP3397753B1 (en) | 2015-12-30 | 2021-10-27 | FUJIFILM Cellular Dynamics, Inc. | Microtissue formation using stem cell-derived human hepatocytes |
| WO2017117571A1 (en) | 2015-12-31 | 2017-07-06 | President And Fellows Of Harvard College | Neurons and compositions and methods for producing the same |
| WO2017117547A1 (en) | 2015-12-31 | 2017-07-06 | President And Fellows Of Harvard College | Methods for generating neural tissue and uses thereof |
| US11021687B2 (en) | 2016-01-08 | 2021-06-01 | The Brigham And Women's Hospital, Inc. | Production of differentiated enteroendocrine cells and insulin producing cells |
| EP3190176A1 (en) | 2016-01-11 | 2017-07-12 | IMBA-Institut für Molekulare Biotechnologie GmbH | Method for tissue culture development on scaffold and differentiated tissue culture |
| HK1256807A1 (zh) | 2016-01-14 | 2019-10-04 | R·阿南德 | 神经类器官组合物及使用方法 |
| US20170205396A1 (en) | 2016-01-15 | 2017-07-20 | Salk Institute For Biological Studies | Systems and methods for culturing nephron progenitor cells |
| EP3411470A4 (en) | 2016-02-01 | 2019-10-09 | Emulate, Inc. | SYSTEMS AND METHOD FOR BREEDING DARM CELLS IN MICROFLUIDIC DEVICES |
| JP7174408B2 (ja) | 2016-02-10 | 2022-11-17 | ウェイク・フォレスト・ユニヴァーシティ・ヘルス・サイエンシズ | 肝線維症のモデル系ならびにその作製および使用方法 |
| WO2017139638A1 (en) | 2016-02-11 | 2017-08-17 | The Johns Hopkins University | Compositions and methods for neuralgenesis |
| JP6947739B2 (ja) | 2016-02-16 | 2021-10-13 | 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 | 既存のヒト中和抗体に対して耐性である新規組換えアデノ随伴ウイルスカプシド |
| WO2017142069A1 (ja) | 2016-02-18 | 2017-08-24 | 学校法人慶應義塾 | 細胞培養培地、培養方法、及びオルガノイド |
| DK3417073T3 (da) | 2016-02-19 | 2023-10-30 | Procella Therapeutics Ab | Genetiske markører til transplantation af humane, hjerteventrikulære progenitorceller |
| US20170267970A1 (en) | 2016-02-29 | 2017-09-21 | Whitehead Institute For Biomedical Research | Three-Dimensional Hydrogels that Support Growth of Physiologically Relevant Tissue and Methods of Use Thereof |
| GB201603569D0 (en) | 2016-03-01 | 2016-04-13 | Koninklijke Nederlandse Akademie Van Wetenschappen | Improved differentiation method |
| US20190086391A1 (en) | 2016-03-08 | 2019-03-21 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Method and system for continuous biosensing |
| WO2017160234A1 (en) | 2016-03-14 | 2017-09-21 | Agency For Science, Technology And Research | Generation of midbrain-specific organoids from human pluripotent stem cells |
| WO2017160671A1 (en) | 2016-03-15 | 2017-09-21 | The Johns Hopkins University | Enhanced organoid formation and intestinal stem cell renewal |
| US10772863B2 (en) | 2016-03-15 | 2020-09-15 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd | Methods of inducing metabolic maturation of human pluripotent stem cells— derived hepatocytes |
| US20170285002A1 (en) | 2016-03-16 | 2017-10-05 | Public University Corporation Yokohama City University | Method for reconstituting tumor with microenvironment |
| WO2017172638A1 (en) | 2016-03-29 | 2017-10-05 | Smsbiotech, Inc. | Compositions and methods for using small mobile stem cells |
| WO2017176810A1 (en) | 2016-04-04 | 2017-10-12 | Biotime, Inc. | Pluripotent stem cell-derived 3d retinal tissue and uses thereof |
| US20190128870A1 (en) | 2016-04-04 | 2019-05-02 | Humeltis | Diagnostic Methods For Patient Specific Therapeutic Decision Making In Cancer Care |
| EP3228306A1 (en) | 2016-04-04 | 2017-10-11 | ratiopharm GmbH | Complex compound comprising obeticholic acid and cyclodextrin and pharmaceutical formulation comprising the complex compound |
| JP6935101B2 (ja) | 2016-04-05 | 2021-09-15 | 学校法人自治医科大学 | 幹細胞を再樹立する方法 |
| EP3445385A4 (en) | 2016-04-18 | 2019-11-20 | The Trustees of Columbia University in the City of New York | THERAPEUTIC GOALS INVOLVED IN THE PROGRESSION OF NON-ALCOHOLIC STEATOHEPATITIS (NASH) |
| CN117137917A (zh) | 2016-04-22 | 2023-12-01 | 景凯生物科技股份有限公司 | 纳美芬、纳曲酮或其衍生物在治疗(非)酒精性脂肪肝炎或非酒精性脂肪性肝病的应用 |
| US20170321188A1 (en) | 2016-05-04 | 2017-11-09 | The Research Foundation For The State University Of New York | Methods of generating retinal progenitor cell preparations and uses thereof |
| CN109415685B (zh) | 2016-05-05 | 2023-07-04 | 儿童医院医疗中心 | 用于体外制造胃底组织的方法和与其相关的组合物 |
| US11760977B2 (en) | 2016-05-25 | 2023-09-19 | Salk Institute For Biological Studies | Compositions and methods for organoid generation and disease modeling |
| US20170349659A1 (en) | 2016-06-03 | 2017-12-07 | The Board Of Trustees Of The Leland Stanford Junior University | Wnt signaling agonist molecules |
| CA3027317A1 (en) | 2016-06-14 | 2017-12-21 | Cellply S.R.L. | Screening kit and method |
| US12129491B2 (en) | 2016-06-15 | 2024-10-29 | Children's Medical Center Corporation | Methods and compositions relating to lung cell differentiation |
| US10221395B2 (en) | 2016-06-16 | 2019-03-05 | Cedars-Sinai Medical Center | Efficient method for reprogramming blood to induced pluripotent stem cells |
| GB201610748D0 (en) | 2016-06-20 | 2016-08-03 | Koninklijke Nederlandse Akademie Van Wetenschappen | Improved diffrentation method |
| GB201611982D0 (en) | 2016-07-11 | 2016-08-24 | Cellesce Ltd | Cell culture |
| EP3275997A1 (en) | 2016-07-28 | 2018-01-31 | QGel SA | Hydrogel precursor formulation and the use thereof |
| KR20190036553A (ko) | 2016-08-02 | 2019-04-04 | 메모리얼 슬로안 케터링 캔서 센터 | 전이성 암의 치료 및 전이성 질환에 대한 모델 시스템 |
| KR20250017294A (ko) | 2016-08-03 | 2025-02-04 | 웨이크 포리스트 유니버시티 헬스 사이언시즈 | 암 모델링 플랫폼 및 그를 사용하는 방법 |
| CA3032727A1 (en) | 2016-08-04 | 2018-02-08 | Wake Forest University Health Sciences | Blood brain barrier model and methods of making and using the same |
| KR102417262B1 (ko) | 2016-08-24 | 2022-07-07 | 각고호우징 게이오기주크 | 인간 설사병 바이러스의 감염·증식 배양용 2d 오가노이드 및 그 사용 |
| JP7262385B2 (ja) | 2016-08-26 | 2023-04-21 | ザ・カウンシル・オブ・ザ・クィーンズランド・インスティテュート・オブ・メディカル・リサーチ | 心筋細胞の成熟 |
| EP3503902A4 (en) | 2016-08-28 | 2020-04-22 | Baylor College of Medicine | A novel chicken egg-based metastasis model for cancer |
| US20210277102A1 (en) | 2016-08-30 | 2021-09-09 | Beth Israel Deaconess Medical Center, Inc. | Compositions and methods for treating a tumor suppressor deficient cancer |
| WO2018044940A1 (en) | 2016-08-30 | 2018-03-08 | Beth Israel Deaconess Medical Center | Compositions and methods for treating a tumor suppressor deficient cancer |
| EP4553082A3 (en) | 2016-11-04 | 2025-08-20 | Children's Hospital Medical Center | Liver organoid compositions and methods of making and using same |
| JP7583524B2 (ja) | 2016-11-23 | 2024-11-14 | モルフォセル テクノロジーズ インコーポレイテッド | 被包化肝組織 |
| EP3548507A4 (en) | 2016-12-05 | 2020-07-15 | Children's Hospital Medical Center | COLON ORGANOIDS AND PROCESSES FOR THE PREPARATION AND USE THEREOF |
| GB201622222D0 (en) | 2016-12-23 | 2017-02-08 | Cs Genetics Ltd | Reagents and methods for molecular barcoding of nucleic acids of single cells |
| JP7248586B2 (ja) | 2017-04-14 | 2023-03-29 | チルドレンズ ホスピタル メディカル センター | 複数ドナー幹細胞組成物およびそれを作製する方法 |
| WO2018200481A1 (en) | 2017-04-24 | 2018-11-01 | Children's Hospital Medical Center | Methods of making improved human intestinal organoid compositions via application of strain and human intestinal organoid compositions thereof |
| EP3395942A1 (en) | 2017-04-25 | 2018-10-31 | IMBA-Institut für Molekulare Biotechnologie GmbH | Bi- or multi-differentiated organoid |
| WO2018226267A1 (en) | 2017-06-09 | 2018-12-13 | Children's Hospital Medical Center | Liver organoid compositions and methods of making and using same |
| EP3694603B1 (en) | 2017-10-10 | 2026-04-08 | Children's Hospital Medical Center | Esophageal tissue and/or organoid compositions and methods of making same |
| EP3727394A4 (en) | 2017-12-21 | 2021-09-08 | Children's Hospital Medical Center | DIGITALIZED HUMAN ORGANOIDS AND METHOD OF USING THEREOF |
| EP4678727A3 (en) | 2018-07-26 | 2026-03-11 | Children's Hospital Medical Center | Hepato-biliary-pancreatic tissues and methods of making same |
| CA3112026A1 (en) | 2018-09-12 | 2020-03-19 | Children's Hospital Medical Center | Organoid compositions for the production of hematopoietic stem cells and derivatives thereof |
| EP3856204A4 (en) | 2018-09-27 | 2022-06-29 | Children's Hospital Medical Center | Liver support system comprising liver organoids and methods of making and using same |
| US12600943B2 (en) | 2019-02-01 | 2026-04-14 | The University Of Hong Kong | Innervated organoid compositions and methods of making same |
-
2017
- 2017-12-05 EP EP17877781.9A patent/EP3548507A4/en active Pending
- 2017-12-05 KR KR1020197018724A patent/KR102558606B1/ko active Active
- 2017-12-05 KR KR1020257015203A patent/KR20250068799A/ko active Pending
- 2017-12-05 CN CN202410839175.5A patent/CN118909916A/zh active Pending
- 2017-12-05 SG SG10202105768WA patent/SG10202105768WA/en unknown
- 2017-12-05 CA CA3045145A patent/CA3045145A1/en active Pending
- 2017-12-05 KR KR1020237024207A patent/KR102807995B1/ko active Active
- 2017-12-05 WO PCT/US2017/064600 patent/WO2018106628A1/en not_active Ceased
- 2017-12-05 NZ NZ753873A patent/NZ753873A/en unknown
- 2017-12-05 CN CN201780073347.0A patent/CN110062764B/zh active Active
- 2017-12-05 US US16/461,147 patent/US11767515B2/en active Active
- 2017-12-05 AU AU2017373767A patent/AU2017373767B2/en active Active
- 2017-12-05 JP JP2019527862A patent/JP7068305B2/ja active Active
-
2019
- 2019-06-05 IL IL267109A patent/IL267109A/en unknown
-
2021
- 2021-12-14 AU AU2021286289A patent/AU2021286289B2/en active Active
-
2022
- 2022-04-28 JP JP2022074275A patent/JP7464652B2/ja active Active
-
2023
- 2023-09-25 US US18/473,619 patent/US20240240154A1/en active Pending
-
2024
- 2024-03-06 AU AU2024201465A patent/AU2024201465A1/en active Pending
- 2024-03-28 JP JP2024052990A patent/JP2024096732A/ja active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130137130A1 (en) * | 2010-05-06 | 2013-05-30 | Children's Hospital Medical Center | Methods and systems for converting precursor cells into intestinal tissues through directed differentiation |
| WO2012168930A2 (en) * | 2011-06-10 | 2012-12-13 | Koninklijke Nederlandse Akademie Van Wetenschappen (Knaw) | Culture media for stem cells |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2024201465A1 (en) | 2024-03-28 |
| KR20250068799A (ko) | 2025-05-16 |
| JP7068305B2 (ja) | 2022-05-16 |
| AU2021286289B2 (en) | 2023-12-14 |
| CN118909916A (zh) | 2024-11-08 |
| US20240240154A1 (en) | 2024-07-18 |
| US20190367882A1 (en) | 2019-12-05 |
| WO2018106628A1 (en) | 2018-06-14 |
| EP3548507A4 (en) | 2020-07-15 |
| CN110062764A (zh) | 2019-07-26 |
| JP7464652B2 (ja) | 2024-04-09 |
| IL267109A (en) | 2019-08-29 |
| AU2021286289A1 (en) | 2022-01-06 |
| CA3045145A1 (en) | 2018-06-14 |
| NZ753873A (en) | 2023-01-27 |
| JP2024096732A (ja) | 2024-07-17 |
| AU2017373767A1 (en) | 2019-06-13 |
| EP3548507A1 (en) | 2019-10-09 |
| JP2020501534A (ja) | 2020-01-23 |
| SG10202105768WA (en) | 2021-06-29 |
| CN110062764B (zh) | 2024-07-02 |
| US11767515B2 (en) | 2023-09-26 |
| JP2022115925A (ja) | 2022-08-09 |
| KR20190088527A (ko) | 2019-07-26 |
| KR20230110839A (ko) | 2023-07-25 |
| KR102807995B1 (ko) | 2025-05-16 |
| AU2017373767B2 (en) | 2021-09-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR102558606B1 (ko) | 결장 유사장기 및 이를 제조 및 사용하는 방법 | |
| JP7420860B2 (ja) | 前駆細胞を指向性分化によって胃組織に変換するための方法及びシステム | |
| DK2898063T3 (en) | PANCREATIC DIFFERENTIALIZATION OF PLURIPOTENT PATTERN CELLS IN VITRO | |
| WO2010007031A2 (en) | Methods for improving cardiac differentiation of human embryonic stem cells | |
| HK40117876A (zh) | 结肠类器官及其制备和使用方法 | |
| HK40011804B (zh) | 结肠类器官及其制备和使用方法 | |
| HK40011804A (en) | Colonic organoids and methods of making and using same | |
| HK40057032A (en) | Methods and systems for converting precursor cells into gastric tissues through directed differentiation | |
| HK40037443A (en) | Methods and systems for converting precursor cells into gastric tissues through directed differentiation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20190627 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| A201 | Request for examination | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 20201130 Comment text: Request for Examination of Application |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20220527 Patent event code: PE09021S01D |
|
| E701 | Decision to grant or registration of patent right | ||
| PE0701 | Decision of registration |
Patent event code: PE07011S01D Comment text: Decision to Grant Registration Patent event date: 20230418 |
|
| GRNT | Written decision to grant | ||
| PR0701 | Registration of establishment |
Comment text: Registration of Establishment Patent event date: 20230719 Patent event code: PR07011E01D |
|
| PR1002 | Payment of registration fee |
Payment date: 20230720 End annual number: 3 Start annual number: 1 |
|
| PG1601 | Publication of registration |