DK3059307T3 - Anvendelse af et laminin til differentiering af pluripotente celler til hepatocyt-cellelinjer - Google Patents
Anvendelse af et laminin til differentiering af pluripotente celler til hepatocyt-cellelinjer Download PDFInfo
- Publication number
- DK3059307T3 DK3059307T3 DK15305265.9T DK15305265T DK3059307T3 DK 3059307 T3 DK3059307 T3 DK 3059307T3 DK 15305265 T DK15305265 T DK 15305265T DK 3059307 T3 DK3059307 T3 DK 3059307T3
- Authority
- DK
- Denmark
- Prior art keywords
- cells
- human
- laminin
- population
- hepatic
- Prior art date
Links
- 210000004027 cell Anatomy 0.000 title claims description 342
- 210000003494 hepatocyte Anatomy 0.000 title claims description 87
- 241000282414 Homo sapiens Species 0.000 claims description 219
- 230000002440 hepatic effect Effects 0.000 claims description 107
- 108010085895 Laminin Proteins 0.000 claims description 87
- 230000004069 differentiation Effects 0.000 claims description 70
- 238000000034 method Methods 0.000 claims description 70
- 102000013529 alpha-Fetoproteins Human genes 0.000 claims description 41
- 108010026331 alpha-Fetoproteins Proteins 0.000 claims description 41
- 210000001900 endoderm Anatomy 0.000 claims description 38
- 230000001605 fetal effect Effects 0.000 claims description 35
- 230000006698 induction Effects 0.000 claims description 33
- 238000012258 culturing Methods 0.000 claims description 28
- 238000000338 in vitro Methods 0.000 claims description 25
- 230000001939 inductive effect Effects 0.000 claims description 22
- 239000011159 matrix material Substances 0.000 claims description 20
- 230000035800 maturation Effects 0.000 claims description 18
- 210000003999 epithelial cell of bile duct Anatomy 0.000 claims description 15
- 108010049955 Bone Morphogenetic Protein 4 Proteins 0.000 claims description 13
- 102100024505 Bone morphogenetic protein 4 Human genes 0.000 claims description 13
- 239000003112 inhibitor Substances 0.000 claims description 12
- 108090000630 Oncostatin M Proteins 0.000 claims description 10
- 108010028309 kalinin Proteins 0.000 claims description 9
- 108010023082 activin A Proteins 0.000 claims description 8
- 239000003102 growth factor Substances 0.000 claims description 8
- 108010038862 laminin 10 Proteins 0.000 claims description 8
- 102000018233 Fibroblast Growth Factor Human genes 0.000 claims description 7
- 108050007372 Fibroblast Growth Factor Proteins 0.000 claims description 7
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 claims description 7
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 claims description 7
- 102300052097 Hepatocyte nuclear factor 4-alpha isoform HNF4-Alpha-2 Human genes 0.000 claims description 7
- 101600072310 Homo sapiens Hepatocyte nuclear factor 4-alpha (isoform HNF4-Alpha-2) Proteins 0.000 claims description 7
- 229940126864 fibroblast growth factor Drugs 0.000 claims description 7
- 102000044880 Wnt3A Human genes 0.000 claims description 6
- 108700013515 Wnt3A Proteins 0.000 claims description 6
- 210000002894 multi-fate stem cell Anatomy 0.000 claims description 6
- 239000011435 rock Substances 0.000 claims description 6
- 102000004140 Oncostatin M Human genes 0.000 claims description 5
- 101150068520 wnt3a gene Proteins 0.000 claims description 5
- 101000917237 Homo sapiens Fibroblast growth factor 10 Proteins 0.000 claims description 2
- 102100028412 Fibroblast growth factor 10 Human genes 0.000 claims 1
- 102000007547 Laminin Human genes 0.000 description 77
- 210000004185 liver Anatomy 0.000 description 74
- 239000002609 medium Substances 0.000 description 50
- 230000014509 gene expression Effects 0.000 description 48
- 108090000623 proteins and genes Proteins 0.000 description 46
- 238000002054 transplantation Methods 0.000 description 42
- 102000004169 proteins and genes Human genes 0.000 description 36
- 235000018102 proteins Nutrition 0.000 description 33
- 150000001875 compounds Chemical class 0.000 description 32
- 239000001963 growth medium Substances 0.000 description 29
- 208000019423 liver disease Diseases 0.000 description 25
- 210000001778 pluripotent stem cell Anatomy 0.000 description 24
- 210000000130 stem cell Anatomy 0.000 description 24
- 102000009027 Albumins Human genes 0.000 description 22
- 108010088751 Albumins Proteins 0.000 description 22
- 150000007523 nucleic acids Chemical class 0.000 description 19
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 18
- 241001465754 Metazoa Species 0.000 description 18
- 108010066302 Keratin-19 Proteins 0.000 description 17
- 230000000694 effects Effects 0.000 description 17
- 102100033420 Keratin, type I cytoskeletal 19 Human genes 0.000 description 16
- 108020004999 messenger RNA Proteins 0.000 description 16
- 102000039446 nucleic acids Human genes 0.000 description 16
- 108020004707 nucleic acids Proteins 0.000 description 16
- 238000011282 treatment Methods 0.000 description 16
- 241000700159 Rattus Species 0.000 description 15
- 210000002966 serum Anatomy 0.000 description 15
- 238000012360 testing method Methods 0.000 description 14
- 102100039203 Cytochrome P450 3A7 Human genes 0.000 description 13
- 101710104801 Cytochrome P450 3A7 Proteins 0.000 description 13
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 13
- 102000015395 alpha 1-Antitrypsin Human genes 0.000 description 13
- 229940024142 alpha 1-antitrypsin Drugs 0.000 description 13
- 108010086524 Hepatocyte Nuclear Factor 4 Proteins 0.000 description 12
- 102000015902 Hepatocyte nuclear factor 4-alpha Human genes 0.000 description 12
- 210000001519 tissue Anatomy 0.000 description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- 238000001727 in vivo Methods 0.000 description 11
- 239000000203 mixture Substances 0.000 description 11
- 102000004328 Cytochrome P-450 CYP3A Human genes 0.000 description 10
- 108010081668 Cytochrome P-450 CYP3A Proteins 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- 230000027455 binding Effects 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- 238000005516 engineering process Methods 0.000 description 10
- 210000004263 induced pluripotent stem cell Anatomy 0.000 description 10
- 230000001172 regenerating effect Effects 0.000 description 10
- 150000001413 amino acids Chemical class 0.000 description 9
- 210000004748 cultured cell Anatomy 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 210000001671 embryonic stem cell Anatomy 0.000 description 9
- 230000012010 growth Effects 0.000 description 9
- 239000003550 marker Substances 0.000 description 9
- 108010082117 matrigel Proteins 0.000 description 9
- 230000002503 metabolic effect Effects 0.000 description 9
- 102000004196 processed proteins & peptides Human genes 0.000 description 9
- 108090000765 processed proteins & peptides Proteins 0.000 description 9
- 230000008672 reprogramming Effects 0.000 description 9
- 238000002965 ELISA Methods 0.000 description 8
- 241000700157 Rattus norvegicus Species 0.000 description 8
- 241000700605 Viruses Species 0.000 description 8
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 8
- 230000035772 mutation Effects 0.000 description 8
- 229920001184 polypeptide Polymers 0.000 description 8
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 7
- 230000008901 benefit Effects 0.000 description 7
- 238000012937 correction Methods 0.000 description 7
- 210000005260 human cell Anatomy 0.000 description 7
- 208000036796 hyperbilirubinemia Diseases 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 230000007170 pathology Effects 0.000 description 7
- 239000008194 pharmaceutical composition Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 230000004083 survival effect Effects 0.000 description 7
- 238000002560 therapeutic procedure Methods 0.000 description 7
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 6
- 108010082126 Alanine transaminase Proteins 0.000 description 6
- 241000713666 Lentivirus Species 0.000 description 6
- 101100310648 Mus musculus Sox17 gene Proteins 0.000 description 6
- 101001062354 Xenopus tropicalis Forkhead box protein A2 Proteins 0.000 description 6
- 230000006378 damage Effects 0.000 description 6
- 210000004039 endoderm cell Anatomy 0.000 description 6
- 239000012634 fragment Substances 0.000 description 6
- 102000008100 Human Serum Albumin Human genes 0.000 description 5
- 108091006905 Human Serum Albumin Proteins 0.000 description 5
- 206010067125 Liver injury Diseases 0.000 description 5
- 238000011529 RT qPCR Methods 0.000 description 5
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 5
- 230000001413 cellular effect Effects 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 230000002443 hepatoprotective effect Effects 0.000 description 5
- 231100000334 hepatotoxic Toxicity 0.000 description 5
- 230000003082 hepatotoxic effect Effects 0.000 description 5
- 230000003908 liver function Effects 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 238000003762 quantitative reverse transcription PCR Methods 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 238000003757 reverse transcription PCR Methods 0.000 description 5
- 238000012216 screening Methods 0.000 description 5
- 230000008093 supporting effect Effects 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 4
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 4
- 208000001819 Crigler-Najjar Syndrome Diseases 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 102100029284 Hepatocyte nuclear factor 3-beta Human genes 0.000 description 4
- 101001062347 Homo sapiens Hepatocyte nuclear factor 3-beta Proteins 0.000 description 4
- 101000848653 Homo sapiens Tripartite motif-containing protein 26 Proteins 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 241000283984 Rodentia Species 0.000 description 4
- -1 UTF-I Proteins 0.000 description 4
- XCCTYIAWTASOJW-XVFCMESISA-N Uridine-5'-Diphosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 XCCTYIAWTASOJW-XVFCMESISA-N 0.000 description 4
- 208000027418 Wounds and injury Diseases 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 239000012472 biological sample Substances 0.000 description 4
- 239000000090 biomarker Substances 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 230000024245 cell differentiation Effects 0.000 description 4
- 238000002659 cell therapy Methods 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000013604 expression vector Substances 0.000 description 4
- 230000009395 genetic defect Effects 0.000 description 4
- 238000011194 good manufacturing practice Methods 0.000 description 4
- 102000046101 human AFP Human genes 0.000 description 4
- 230000000977 initiatory effect Effects 0.000 description 4
- 208000014674 injury Diseases 0.000 description 4
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000008929 regeneration Effects 0.000 description 4
- 238000011069 regeneration method Methods 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 230000004936 stimulating effect Effects 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 239000013598 vector Substances 0.000 description 4
- 101710149366 Afamin Proteins 0.000 description 3
- 101100257359 Caenorhabditis elegans sox-2 gene Proteins 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 3
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 3
- 108091008794 FGF receptors Proteins 0.000 description 3
- 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 101000652324 Homo sapiens Transcription factor SOX-17 Proteins 0.000 description 3
- 206010061598 Immunodeficiency Diseases 0.000 description 3
- 241001529936 Murinae Species 0.000 description 3
- 101100257363 Mus musculus Sox2 gene Proteins 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 3
- 101710126211 POU domain, class 5, transcription factor 1 Proteins 0.000 description 3
- 108010029485 Protein Isoforms Proteins 0.000 description 3
- 102000001708 Protein Isoforms Human genes 0.000 description 3
- 238000010240 RT-PCR analysis Methods 0.000 description 3
- 206010043276 Teratoma Diseases 0.000 description 3
- 102100030243 Transcription factor SOX-17 Human genes 0.000 description 3
- 229940024606 amino acid Drugs 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 208000027119 bilirubin metabolic disease Diseases 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 210000002744 extracellular matrix Anatomy 0.000 description 3
- 238000000684 flow cytometry Methods 0.000 description 3
- 238000001415 gene therapy Methods 0.000 description 3
- 238000003306 harvesting Methods 0.000 description 3
- 231100000234 hepatic damage Toxicity 0.000 description 3
- 108700002956 human laminin 11 Proteins 0.000 description 3
- 102000044407 human laminin 11 Human genes 0.000 description 3
- 238000010185 immunofluorescence analysis Methods 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- 239000007928 intraperitoneal injection Substances 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 108010057670 laminin 1 Proteins 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 230000008818 liver damage Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000007102 metabolic function Effects 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 238000012753 partial hepatectomy Methods 0.000 description 3
- 230000002062 proliferating effect Effects 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 239000002753 trypsin inhibitor Substances 0.000 description 3
- 208000030954 urea cycle disease Diseases 0.000 description 3
- 239000013603 viral vector Substances 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 108010059616 Activins Proteins 0.000 description 2
- 102000005606 Activins Human genes 0.000 description 2
- 208000007788 Acute Liver Failure Diseases 0.000 description 2
- 206010000804 Acute hepatic failure Diseases 0.000 description 2
- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 2
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 2
- WMTIOGUVKBSEOW-UHFFFAOYSA-N ClC1(Cl)OP(=O)OP(=O)O1 Chemical compound ClC1(Cl)OP(=O)OP(=O)O1 WMTIOGUVKBSEOW-UHFFFAOYSA-N 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 2
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 102000016354 Glucuronosyltransferase Human genes 0.000 description 2
- 108010092364 Glucuronosyltransferase Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 108060003393 Granulin Proteins 0.000 description 2
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 2
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 206010019663 Hepatic failure Diseases 0.000 description 2
- 208000021177 Hepatic metabolic disease Diseases 0.000 description 2
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 2
- 102100021866 Hepatocyte growth factor Human genes 0.000 description 2
- 206010019851 Hepatotoxicity Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101001139134 Homo sapiens Krueppel-like factor 4 Proteins 0.000 description 2
- 101000687905 Homo sapiens Transcription factor SOX-2 Proteins 0.000 description 2
- 102100020677 Krueppel-like factor 4 Human genes 0.000 description 2
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 2
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- 108091061960 Naked DNA Proteins 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- 102000010292 Peptide Elongation Factor 1 Human genes 0.000 description 2
- 108010077524 Peptide Elongation Factor 1 Proteins 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 2
- 102100024270 Transcription factor SOX-2 Human genes 0.000 description 2
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 2
- 102000004357 Transferases Human genes 0.000 description 2
- 108090000992 Transferases Proteins 0.000 description 2
- 102100031358 Urokinase-type plasminogen activator Human genes 0.000 description 2
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 2
- 239000000488 activin Substances 0.000 description 2
- 231100000836 acute liver failure Toxicity 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 210000004436 artificial bacterial chromosome Anatomy 0.000 description 2
- 210000002469 basement membrane Anatomy 0.000 description 2
- 229940112869 bone morphogenetic protein Drugs 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000010494 dissociation reaction Methods 0.000 description 2
- 230000005593 dissociations Effects 0.000 description 2
- 230000005014 ectopic expression Effects 0.000 description 2
- 210000004700 fetal blood Anatomy 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 108091006047 fluorescent proteins Proteins 0.000 description 2
- 102000034287 fluorescent proteins Human genes 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000001476 gene delivery Methods 0.000 description 2
- 238000012239 gene modification Methods 0.000 description 2
- 238000010362 genome editing Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 208000007345 glycogen storage disease Diseases 0.000 description 2
- 239000005090 green fluorescent protein Substances 0.000 description 2
- 231100000753 hepatic injury Toxicity 0.000 description 2
- 208000002672 hepatitis B Diseases 0.000 description 2
- 230000001553 hepatotropic effect Effects 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 230000002487 hyperbilirubinemic effect Effects 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 208000015978 inherited metabolic disease Diseases 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 230000008611 intercellular interaction Effects 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 230000031142 liver development Effects 0.000 description 2
- 231100000835 liver failure Toxicity 0.000 description 2
- 208000007903 liver failure Diseases 0.000 description 2
- 230000005923 long-lasting effect Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 208000002780 macular degeneration Diseases 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 108091070501 miRNA Proteins 0.000 description 2
- 239000002679 microRNA Substances 0.000 description 2
- 230000000926 neurological effect Effects 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 101150093826 par1 gene Proteins 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 239000013600 plasmid vector Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000002629 repopulating effect Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 235000002639 sodium chloride Nutrition 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 229960001967 tacrolimus Drugs 0.000 description 2
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 108091005957 yellow fluorescent proteins Proteins 0.000 description 2
- OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical compound C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-N 0.000 description 1
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- 108091064702 1 family Proteins 0.000 description 1
- YMHOBZXQZVXHBM-UHFFFAOYSA-N 2,5-dimethoxy-4-bromophenethylamine Chemical compound COC1=CC(CCN)=C(OC)C=C1Br YMHOBZXQZVXHBM-UHFFFAOYSA-N 0.000 description 1
- MEAPRSDUXBHXGD-UHFFFAOYSA-N 3-chloro-n-(4-propan-2-ylphenyl)propanamide Chemical compound CC(C)C1=CC=C(NC(=O)CCCl)C=C1 MEAPRSDUXBHXGD-UHFFFAOYSA-N 0.000 description 1
- 238000010146 3D printing Methods 0.000 description 1
- 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 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- ORILYTVJVMAKLC-UHFFFAOYSA-N Adamantane Natural products C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 1
- 239000012103 Alexa Fluor 488 Substances 0.000 description 1
- 101710189683 Alkaline protease 1 Proteins 0.000 description 1
- 101710154562 Alkaline proteinase Proteins 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- ITPDYQOUSLNIHG-UHFFFAOYSA-N Amiodarone hydrochloride Chemical compound [Cl-].CCCCC=1OC2=CC=CC=C2C=1C(=O)C1=CC(I)=C(OCC[NH+](CC)CC)C(I)=C1 ITPDYQOUSLNIHG-UHFFFAOYSA-N 0.000 description 1
- 108091093088 Amplicon Proteins 0.000 description 1
- 101710170876 Antileukoproteinase Proteins 0.000 description 1
- 101710081722 Antitrypsin Proteins 0.000 description 1
- 108091023037 Aptamer Proteins 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 108091005950 Azurite Proteins 0.000 description 1
- 239000012583 B-27 Supplement Substances 0.000 description 1
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 1
- 208000033222 Biliary cirrhosis primary Diseases 0.000 description 1
- 102100033743 Biotin-[acetyl-CoA-carboxylase] ligase Human genes 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101710112538 C-C motif chemokine 27 Proteins 0.000 description 1
- 238000010453 CRISPR/Cas method Methods 0.000 description 1
- 102000000905 Cadherin Human genes 0.000 description 1
- 108050007957 Cadherin Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 241000427950 Carpentiera Species 0.000 description 1
- 102100035882 Catalase Human genes 0.000 description 1
- 108010053835 Catalase Proteins 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000315055 Cercospora hayi Species 0.000 description 1
- 108091005944 Cerulean Proteins 0.000 description 1
- 206010008609 Cholangitis sclerosing Diseases 0.000 description 1
- 206010008909 Chronic Hepatitis Diseases 0.000 description 1
- 108091005960 Citrine Proteins 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
- 241000699800 Cricetinae Species 0.000 description 1
- 208000012483 Crigler-Najjar syndrome type 1 Diseases 0.000 description 1
- 108091005943 CyPet Proteins 0.000 description 1
- 108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 description 1
- 102100036252 Cyclin-dependent kinase 4 Human genes 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 108091005941 EBFP Proteins 0.000 description 1
- 108091005947 EBFP2 Proteins 0.000 description 1
- 108091005942 ECFP Proteins 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 208000010334 End Stage Liver Disease Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 108020004206 Gamma-glutamyltransferase Proteins 0.000 description 1
- 241000699694 Gerbillinae Species 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 208000031220 Hemophilia Diseases 0.000 description 1
- 208000009292 Hemophilia A Diseases 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 208000002972 Hepatolenticular Degeneration Diseases 0.000 description 1
- 101150068639 Hnf4a gene Proteins 0.000 description 1
- 101000823116 Homo sapiens Alpha-1-antitrypsin Proteins 0.000 description 1
- 101000827785 Homo sapiens Alpha-fetoprotein Proteins 0.000 description 1
- 101000871771 Homo sapiens Biotin-[acetyl-CoA-carboxylase] ligase Proteins 0.000 description 1
- 101000762379 Homo sapiens Bone morphogenetic protein 4 Proteins 0.000 description 1
- 101100281008 Homo sapiens FGF2 gene Proteins 0.000 description 1
- 101000898034 Homo sapiens Hepatocyte growth factor Proteins 0.000 description 1
- 101000992170 Homo sapiens Oncostatin-M Proteins 0.000 description 1
- 101001094700 Homo sapiens POU domain, class 5, transcription factor 1 Proteins 0.000 description 1
- 101000954805 Homo sapiens Protein Wnt-3a Proteins 0.000 description 1
- 101000984042 Homo sapiens Protein lin-28 homolog A Proteins 0.000 description 1
- 101000669917 Homo sapiens Rho-associated protein kinase 1 Proteins 0.000 description 1
- 101000669921 Homo sapiens Rho-associated protein kinase 2 Proteins 0.000 description 1
- 208000000563 Hyperlipoproteinemia Type II Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 208000028547 Inborn Urea Cycle disease Diseases 0.000 description 1
- 208000008498 Infantile Refsum disease Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 108700021430 Kruppel-Like Factor 4 Proteins 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 description 1
- 208000035719 Maculopathy Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 108060004795 Methyltransferase Proteins 0.000 description 1
- 102000016397 Methyltransferase Human genes 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 208000012654 Primary biliary cholangitis Diseases 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 102100025460 Protein lin-28 homolog A Human genes 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 108010067787 Proteoglycans Proteins 0.000 description 1
- 102000016611 Proteoglycans Human genes 0.000 description 1
- 102000014450 RNA Polymerase III Human genes 0.000 description 1
- 108010078067 RNA Polymerase III Proteins 0.000 description 1
- 238000011530 RNeasy Mini Kit Methods 0.000 description 1
- 101100247004 Rattus norvegicus Qsox1 gene Proteins 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- JRZNNZYZXQFKCF-UHFFFAOYSA-N Retrorsine Natural products CC=C/1CC(C)C(C)(CO)C(=O)OCC2CCN3CCC(OC1=O)C23 JRZNNZYZXQFKCF-UHFFFAOYSA-N 0.000 description 1
- 102100039313 Rho-associated protein kinase 1 Human genes 0.000 description 1
- 102100039314 Rho-associated protein kinase 2 Human genes 0.000 description 1
- 238000011579 SCID mouse model Methods 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 108091027967 Small hairpin RNA Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 108010092262 T-Cell Antigen Receptors Proteins 0.000 description 1
- 238000010459 TALEN Methods 0.000 description 1
- 238000008050 Total Bilirubin Reagent Methods 0.000 description 1
- 108010043645 Transcription Activator-Like Effector Nucleases Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 206010045261 Type IIa hyperlipidaemia Diseases 0.000 description 1
- 108010032099 V(D)J recombination activating protein 2 Proteins 0.000 description 1
- 102100029591 V(D)J recombination-activating protein 2 Human genes 0.000 description 1
- 241000545067 Venus Species 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 208000018839 Wilson disease Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 108010076089 accutase Proteins 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 206010064930 age-related macular degeneration Diseases 0.000 description 1
- 230000004520 agglutination Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 238000011129 allogeneic cell therapy Methods 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 description 1
- 235000020661 alpha-linolenic acid Nutrition 0.000 description 1
- 229960005260 amiodarone Drugs 0.000 description 1
- 210000003663 amniotic stem cell Anatomy 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001475 anti-trypsic effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 210000004507 artificial chromosome Anatomy 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- BCJMNZRQJAVDLD-PDOBJIDASA-N beta-longilobine Natural products CC=C1C[C@H](C)[C@@](O)(CO)C(=O)OCC2=CCN3CC[C@@H](OC1=O)[C@H]23 BCJMNZRQJAVDLD-PDOBJIDASA-N 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- BPYKTIZUTYGOLE-UHFFFAOYSA-N billirubin-IXalpha Natural products N1C(=O)C(C)=C(C=C)C1=CC1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(C=C3C(=C(C=C)C(=O)N3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-UHFFFAOYSA-N 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 108091005948 blue fluorescent proteins Proteins 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000011748 cell maturation Effects 0.000 description 1
- 230000032341 cell morphogenesis Effects 0.000 description 1
- 230000009087 cell motility Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000002458 cell surface marker Substances 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 210000001612 chondrocyte Anatomy 0.000 description 1
- 238000007813 chromatographic assay Methods 0.000 description 1
- 208000011444 chronic liver failure Diseases 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 239000011035 citrine Substances 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000003501 co-culture Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 239000013601 cosmid vector Substances 0.000 description 1
- 238000005138 cryopreservation Methods 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 108010082025 cyan fluorescent protein Proteins 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 210000003981 ectoderm Anatomy 0.000 description 1
- 230000010102 embolization Effects 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 201000001386 familial hypercholesterolemia Diseases 0.000 description 1
- 208000019298 familial intrahepatic cholestasis Diseases 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000010230 functional analysis Methods 0.000 description 1
- 102000006640 gamma-Glutamyltransferase Human genes 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000005017 genetic modification Effects 0.000 description 1
- 235000013617 genetically modified food Nutrition 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 210000001654 germ layer Anatomy 0.000 description 1
- 230000023611 glucuronidation Effects 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 229960003711 glyceryl trinitrate Drugs 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 208000035474 group of disease Diseases 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 230000007686 hepatotoxicity Effects 0.000 description 1
- 231100000784 hepatotoxin Toxicity 0.000 description 1
- 230000003494 hepatotrophic effect Effects 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 102000046148 human BMP4 Human genes 0.000 description 1
- 102000057243 human FGF10 Human genes 0.000 description 1
- 102000057308 human HGF Human genes 0.000 description 1
- 102000043703 human OSM Human genes 0.000 description 1
- 102000052983 human POU5F1 Human genes 0.000 description 1
- 102000056781 human WNT3A Human genes 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000003365 immunocytochemistry Methods 0.000 description 1
- 238000000760 immunoelectrophoresis Methods 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 208000016245 inborn errors of metabolism Diseases 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 101150111214 lin-28 gene Proteins 0.000 description 1
- 229960004488 linolenic acid Drugs 0.000 description 1
- KQQKGWQCNNTQJW-UHFFFAOYSA-N linolenic acid Natural products CC=CCCC=CCC=CCCCCCCCC(O)=O KQQKGWQCNNTQJW-UHFFFAOYSA-N 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 235000019136 lipoic acid Nutrition 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 238000007449 liver function test Methods 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 230000002101 lytic effect Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 210000003716 mesoderm Anatomy 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- BCJMNZRQJAVDLD-HVFZGPLGSA-N mucronatinine Natural products CC=C1C[C@H](C)[C@@](O)(CO)C(=O)OCC2=CCN3CC[C@@H](OC1=O)[C@@H]23 BCJMNZRQJAVDLD-HVFZGPLGSA-N 0.000 description 1
- 108091005763 multidomain proteins Proteins 0.000 description 1
- 238000013188 needle biopsy Methods 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229960000564 nitrofurantoin Drugs 0.000 description 1
- NXFQHRVNIOXGAQ-YCRREMRBSA-N nitrofurantoin Chemical compound O1C([N+](=O)[O-])=CC=C1\C=N\N1C(=O)NC(=O)C1 NXFQHRVNIOXGAQ-YCRREMRBSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 238000003499 nucleic acid array Methods 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000000050 nutritive effect Effects 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 230000005868 ontogenesis Effects 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 239000000123 paper Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 238000001126 phototherapy Methods 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 201000000742 primary sclerosing cholangitis Diseases 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 229960004604 propranolol hydrochloride Drugs 0.000 description 1
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol hydrochloride Natural products C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000001860 quasi-elastic neutron scattering Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 210000003583 retinal pigment epithelium Anatomy 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 208000010157 sclerosing cholangitis Diseases 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000004055 small Interfering RNA Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000001082 somatic cell Anatomy 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 210000001988 somatic stem cell Anatomy 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000003393 splenic effect Effects 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000009168 stem cell therapy Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000003319 supportive effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 239000003104 tissue culture media Substances 0.000 description 1
- 230000025366 tissue development Effects 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- 238000009602 toxicology test Methods 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- GWBUNZLLLLDXMD-UHFFFAOYSA-H tricopper;dicarbonate;dihydroxide Chemical compound [OH-].[OH-].[Cu+2].[Cu+2].[Cu+2].[O-]C([O-])=O.[O-]C([O-])=O GWBUNZLLLLDXMD-UHFFFAOYSA-H 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000005740 tumor formation Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 201000011296 tyrosinemia Diseases 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- BCJMNZRQJAVDLD-XKLVTHTNSA-N β-Longilobine Chemical compound O1C(=O)C(=CC)C[C@@H](C)[C@](O)(CO)C(=O)OCC2=CCN3[C@H]2[C@H]1CC3 BCJMNZRQJAVDLD-XKLVTHTNSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/067—Hepatocytes
- C12N5/0672—Stem cells; Progenitor cells; Precursor cells; Oval 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
- 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
- C12N5/067—Hepatocytes
-
- 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
- C12N2500/00—Specific components of cell culture medium
- C12N2500/98—Xeno-free medium and culture conditions
-
- 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
- C12N2501/119—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
- C12N2501/12—Hepatocyte growth factor [HGF]
-
- 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
- C12N2501/20—Cytokines; Chemokines
- C12N2501/237—Oncostatin M [OSM]
-
- 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
- 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
- C12N2533/00—Supports or coatings for cell culture, characterised by material
- C12N2533/50—Proteins
- C12N2533/52—Fibronectin; Laminin
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biomedical Technology (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Chemical & Material Sciences (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Cell Biology (AREA)
- Developmental Biology & Embryology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
Claims (11)
1. Anvendelse in vitro af et humant laminin (LN) som en matrix til hepatisk differentiering.
2. Anvendelse in vitro af et humant LN til induktion og/eller forbedret differentiering af en population af pluripotente celler, en population af multipotente celler eller en population af definitive endoderme (DE) celler til en population af hepatocyt-cellelinjer.
3. Anvendelse ifølge krav 1 eller 2, hvor LN er valgt fra gruppen bestående af laminin-111 (LN-111), laminin-211 (LN-211), laminin-332 (LN-332), laminin-411 (LN-411), laminin-421 (LN-421), laminin-511 (LN-511)og laminin-521 (LN-521).
4. Anvendelse ifølge et hvilket som helst af kravene 1 til 3, hvor LN er human rekombinant LN-111 eller human rekombinant LN-521.
5. Fremgangsmåde in vitro til induktion af human hepatisk differentiering, der omfatter følgende trin: (i) dyrkning af en population af humane DE-celler på en bærer coatet med et humant laminin i et hepatisk induktionsmedium for at frembringe en population af humane hepatoblast-lignende celler, og (ii) dyrkning af populationen af humane hepatoblast-lignende celler på en bærer coatet med et humant laminin i et hepatisk modningsmedium for at frembringe en population af humane føtale hepatocyt-lignende celler.
6. Fremgangsmåde in vitro til induktion af human hepatisk differentiering, der omfatter følgende trin: (i) dyrkning af en population af humane pluripotente celler på en bærer coatet med et humant laminin i et endodermt induktionsmedium for at frembringe en population af humane DE-celler, (ii) dyrkning af populationen af humane DE-celler på en bærer coatet med et humant laminin i et hepatisk induktionsmedium for at frembringe en population af humane hepatoblast-lignende celler, og (iii) dyrkning af populationen af humane hepatoblast-lignende celler på en bærer coatet med et humant laminin i et hepatisk modningsmedium for at frembringe en population af humane føtale hepatocyt-lignende celler.
7. Fremgangsmåde in vitro ifølge krav 5 eller 6, hvor det hepatiske induktionsmedium er et kemisk defineret medium, der omfatter knoglemorfogenetisk protein 4 (BMP4) og en fibroblast-vækstfaktor valgt fra FGF10 og FGF2.
8. Fremgangsmåde in vitro ifølge et hvilket som helst af kravene 5 til 7, hvor det hepatiske modningsmedium er et kemisk defineret medium, der omfatter hepatisk vækstfaktor (HGF) og oncostatin M (OSM).
9. Fremgangsmåde in vitro ifølge krav 6, hvor det endoderme induktionsmedium er et kemisk defineret medium, der omfatter mindst Activin A og eventuelt WNT3A.
10. Fremgangsmåde in vitro ifølge et hvilket som helst af kravene 5 til 9, hvor det hepatiske induktionsmedium og/eller det endoderme induktionsmedium endvidere omfatter en ROCK-hæmmer.
11. Fremgangsmåde in vitro ifølge et hvilket som helst af kravene 5 til 10, hvor de humane hepatoblast-lignende celler udtrykker hepatocyt-nuklearfaktor 4-alpha (HNF4a) og ikke eller i alt væsentligt ikke udtrykker alpha-fetoprotein (AFP).
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP15305265.9A EP3059307B2 (en) | 2015-02-20 | 2015-02-20 | Use of a laminin for differentiating pluripotent cells into hepatocyte lineage cells |
Publications (3)
Publication Number | Publication Date |
---|---|
DK3059307T3 true DK3059307T3 (da) | 2019-01-14 |
DK3059307T4 DK3059307T4 (da) | 2022-08-01 |
DK3059307T5 DK3059307T5 (da) | 2022-08-29 |
Family
ID=52598699
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DK15305265.9T DK3059307T5 (da) | 2015-02-20 | 2015-02-20 | Anvendelse af et laminin til differentiering af pluripotente celler i hepatocytcellelinier |
DK16705202.6T DK3259345T5 (da) | 2015-02-20 | 2016-02-19 | Anvendelse af laminin til differentiering af pluripotente celler i hepatocyt-linie-celler |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DK16705202.6T DK3259345T5 (da) | 2015-02-20 | 2016-02-19 | Anvendelse af laminin til differentiering af pluripotente celler i hepatocyt-linie-celler |
Country Status (17)
Country | Link |
---|---|
US (2) | US20180030415A1 (da) |
EP (2) | EP3059307B2 (da) |
JP (2) | JP6840084B2 (da) |
CN (2) | CN107532144A (da) |
CA (1) | CA2986830A1 (da) |
CY (1) | CY1121243T1 (da) |
DK (2) | DK3059307T5 (da) |
ES (2) | ES2703167T5 (da) |
FI (1) | FI3259345T3 (da) |
HR (2) | HRP20182119T4 (da) |
HU (2) | HUE041518T2 (da) |
LT (2) | LT3059307T (da) |
PL (2) | PL3059307T5 (da) |
PT (2) | PT3059307T (da) |
RS (2) | RS58070B2 (da) |
SI (2) | SI3059307T2 (da) |
WO (1) | WO2016131959A1 (da) |
Families Citing this family (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014011095A1 (en) * | 2012-07-12 | 2014-01-16 | Isletone Ab | Derivation and self-renewal of isi1+ cells and uses thereof |
RS58070B2 (sr) * | 2015-02-20 | 2022-10-31 | Inst Nat Sante Rech Med | Upotreba laminina za diferencijaciju pluripotentnih ćelija u ćelije hepatocitne linije |
EP3368657B1 (en) | 2015-10-30 | 2021-06-30 | Biolamina AB | Methods for producing hepatocytes |
JP7209619B2 (ja) * | 2016-07-28 | 2023-01-20 | エフ.ホフマン-ラ ロシュ アーゲー | 非ヒト霊長類人工多能性幹細胞由来肝細胞およびその使用 |
KR102516844B1 (ko) * | 2016-11-16 | 2023-04-04 | 시나타 세라퓨틱스 엘티디 | 만능성 줄기 세포 분석 |
WO2018152120A1 (en) | 2017-02-14 | 2018-08-23 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Methods of engineering human induced pluripotent stem cells to produce liver tissue |
JP6950887B2 (ja) * | 2017-04-28 | 2021-10-13 | 米満 吉和 | 体外型の人工肝臓、及び体外型の人工肝臓用又は肝細胞培養用の器具 |
AU2018262323A1 (en) | 2017-05-05 | 2019-11-21 | National University Of Singapore | Methods for culturing human keratinocytes |
BR112020013656A2 (pt) | 2018-01-05 | 2020-12-01 | Platelet Biogenesis, Inc. | composições e métodos para produção de megacariócitos |
EP3794107A1 (en) * | 2018-05-16 | 2021-03-24 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Method of culturing proliferative hepatocytes |
EP3813853A4 (en) * | 2018-06-29 | 2022-04-06 | Platelet Biogenesis, Inc. | DELIVERY COMPOSITIONS AND METHODS OF USE |
US11227435B2 (en) | 2018-08-13 | 2022-01-18 | Magic Leap, Inc. | Cross reality system |
CN117802031A (zh) * | 2018-09-30 | 2024-04-02 | 中国科学院分子细胞科学卓越创新中心 | 肝细胞的体外扩增培养方法及应用 |
US20210395679A1 (en) * | 2018-11-09 | 2021-12-23 | Children's Hospital Medical Center | In vitro cell culture system for producing hepatocyte-like cells and uses thereof |
CN111621467A (zh) * | 2020-06-12 | 2020-09-04 | 青岛大学 | 一种诱导人脂肪间充质干细胞分化为肝脏样细胞的方法 |
CN115851578B (zh) * | 2022-12-23 | 2023-11-21 | 华南理工大学 | 一种3d悬浮诱导持续扩增肝祖细胞类器官和/或肝细胞类器官的试剂盒及其应用 |
Family Cites Families (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5843780A (en) | 1995-01-20 | 1998-12-01 | Wisconsin Alumni Research Foundation | Primate embryonic stem cells |
JP2005095138A (ja) * | 2003-08-19 | 2005-04-14 | Effector Cell Institute Inc | 多分化能を有する細胞の分化誘導方法 |
US7332336B2 (en) * | 2003-08-19 | 2008-02-19 | Effector Cell Institute, Inc. | Methods for inducing differentiation of pluripotent cells |
WO2006040763A2 (en) | 2004-10-12 | 2006-04-20 | Technion Research & Development Foundation Ltd. | Isolated primate embryonic cells and methods of generating and using same |
US8048999B2 (en) | 2005-12-13 | 2011-11-01 | Kyoto University | Nuclear reprogramming factor |
US8741643B2 (en) * | 2006-04-28 | 2014-06-03 | Lifescan, Inc. | Differentiation of pluripotent stem cells to definitive endoderm lineage |
US8951799B2 (en) * | 2007-01-04 | 2015-02-10 | Biolamina Ab | Composition and method for enabling proliferation of pluripotent stem cells |
WO2009013254A1 (en) * | 2007-07-20 | 2009-01-29 | Cellartis Ab | A novel population of hepatocytes derived via definitive endoderm (de-hep) from human blastocysts stem cells |
CA2660123C (en) | 2007-10-31 | 2017-05-09 | Kyoto University | Nuclear reprogramming method |
JP2011516042A (ja) | 2008-03-17 | 2011-05-26 | へルムホルツ・ツェントルム・ミュンヘン−ドイチェス・フォルシュングスツェントルム・ヒューア・ゲズントハイト・ウント・ウムヴェルト(ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング) | 部位特異的組み換えを用いて無ベクター誘導多能性幹(iPS)細胞を作製するベクターおよびその方法 |
WO2010042490A1 (en) | 2008-10-06 | 2010-04-15 | Boston Medical Center Corporation | A single lentiviral vector system for induced pluripotent (ips) stem cells derivation |
WO2010140464A1 (ja) * | 2009-06-05 | 2010-12-09 | 国立大学法人 熊本大学 | 細胞の分化誘導方法 |
JP5745423B2 (ja) * | 2009-10-28 | 2015-07-08 | 公益財団法人ヒューマンサイエンス振興財団 | 幹細胞から肝細胞への分化誘導方法 |
US9127255B2 (en) * | 2010-06-11 | 2015-09-08 | Takara Bio Europe Ab | 3-dimensional scaffolds for improved differentiation of pluripotent stem cells to hepatocytes |
WO2012080842A1 (en) | 2010-12-17 | 2012-06-21 | Biolamina Ab | Recombinant laminin-521 |
US10240124B2 (en) * | 2011-09-22 | 2019-03-26 | Biolamina Ab | Cell culture substrate comprising a laminin and a cadherin |
US20130330825A1 (en) * | 2012-06-07 | 2013-12-12 | City Of Hope | Attachment substrates for directed differentiation of human embryonic stem cells in culture |
JP5858411B2 (ja) * | 2012-12-28 | 2016-02-10 | 国立大学法人大阪大学 | コラーゲン結合性分子を付加した改変ラミニンおよびその利用 |
SG11201506520TA (en) * | 2013-02-18 | 2015-09-29 | Univ Health Network | Methods for generating hepatocytes and cholangiocytes from pluripotent stem cells |
US20160046904A1 (en) † | 2013-04-08 | 2016-02-18 | National Institutes Of Biomedical Innovation, Health And Nutrition | Method For Culturing Hepatoblast-Like Cells And Culture Product Thereof |
RS58070B2 (sr) | 2015-02-20 | 2022-10-31 | Inst Nat Sante Rech Med | Upotreba laminina za diferencijaciju pluripotentnih ćelija u ćelije hepatocitne linije |
-
2015
- 2015-02-20 RS RS20181530A patent/RS58070B2/sr unknown
- 2015-02-20 LT LTEP15305265.9T patent/LT3059307T/lt unknown
- 2015-02-20 DK DK15305265.9T patent/DK3059307T5/da active
- 2015-02-20 HR HRP20182119TT patent/HRP20182119T4/hr unknown
- 2015-02-20 HU HUE15305265A patent/HUE041518T2/hu unknown
- 2015-02-20 ES ES15305265T patent/ES2703167T5/es active Active
- 2015-02-20 PT PT15305265T patent/PT3059307T/pt unknown
- 2015-02-20 EP EP15305265.9A patent/EP3059307B2/en active Active
- 2015-02-20 PL PL15305265.9T patent/PL3059307T5/pl unknown
- 2015-02-20 SI SI201530533T patent/SI3059307T2/sl unknown
-
2016
- 2016-02-19 RS RS20230211A patent/RS64062B1/sr unknown
- 2016-02-19 HU HUE16705202A patent/HUE061457T2/hu unknown
- 2016-02-19 FI FIEP16705202.6T patent/FI3259345T3/fi active
- 2016-02-19 CN CN201680010458.2A patent/CN107532144A/zh active Pending
- 2016-02-19 HR HRP20230302TT patent/HRP20230302T1/hr unknown
- 2016-02-19 EP EP16705202.6A patent/EP3259345B1/en active Active
- 2016-02-19 CA CA2986830A patent/CA2986830A1/en active Pending
- 2016-02-19 WO PCT/EP2016/053560 patent/WO2016131959A1/en active Application Filing
- 2016-02-19 PL PL16705202.6T patent/PL3259345T3/pl unknown
- 2016-02-19 DK DK16705202.6T patent/DK3259345T5/da active
- 2016-02-19 LT LTEPPCT/EP2016/053560T patent/LT3259345T/lt unknown
- 2016-02-19 JP JP2017543392A patent/JP6840084B2/ja active Active
- 2016-02-19 ES ES16705202T patent/ES2940191T3/es active Active
- 2016-02-19 US US15/551,551 patent/US20180030415A1/en not_active Abandoned
- 2016-02-19 PT PT167052026T patent/PT3259345T/pt unknown
- 2016-02-19 CN CN202010391416.6A patent/CN111548985A/zh active Pending
- 2016-02-19 SI SI201631673T patent/SI3259345T1/sl unknown
-
2018
- 2018-12-14 CY CY20181101344T patent/CY1121243T1/el unknown
-
2020
- 2020-10-01 JP JP2020167137A patent/JP7132463B2/ja active Active
-
2023
- 2023-11-17 US US18/512,545 patent/US20240150721A1/en active Pending
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20240150721A1 (en) | Use of a Laminin for Differentiating Pluripotent Cells into Hepatocyte Lineage Cells | |
JP2018508207A5 (da) | ||
RU2579995C2 (ru) | Органоид печени, варианты его применения и способ культивирования для его получения | |
US9005964B2 (en) | Endodermal progenitor cells | |
Dianat et al. | Human pluripotent stem cells for modelling human liver diseases and cell therapy | |
US10526581B2 (en) | Modulation of cardiac stem-progenitor cell differentiation, assays and uses thereof | |
US20130031645A1 (en) | Method for hepatic differentiation of definitive endoderm cells | |
Sung et al. | Effect of cell culture biomaterials for completely xeno-free generation of human induced pluripotent stem cells | |
JP2018068307A (ja) | 再プログラム化多能性細胞の作製 | |
US20140023624A1 (en) | Decellularized liver transplantation composition and methods | |
WO2011016485A1 (ja) | iPS細胞から肝実質細胞への分化誘導方法 | |
JP7203427B2 (ja) | ヒト人工多能性幹細胞を操作して肝臓組織を作製する方法 | |
Schmelzer et al. | Hepatic stem cells and the liver’s maturational lineages: Implications for liver biology, gene expression, and cell therapies | |
WO2019055345A1 (en) | COMPOSITIONS AND METHODS FOR TREATING HEPATIC DISEASE AND HEPATIC DYSFUNCTION | |
CN111849859A (zh) | 一种经基因编辑的功能性肝实质细胞的制备方法及其应用 | |
Wei et al. | Infarcted cardiac microenvironment may hinder cardiac lineage differentiation of human embryonic stem cells | |
Tafaleng | Modeling the personalized variations in liver disease due to α1-antitrypsin deficiency using induced pluripotent stem cell-derived hepatocyte-like cells | |
Muggeo | A STEP-BY-STEP PROCESS TO GENERATE FUNCTIONAL OSTEOCLASTS FROM SITE SPECIFIC GENE-CORRECTED INDUCED PLURIPOTENT STEM CELLS: AN AUTOLOGOUS CELL THERAPY APPROACH TO TREAT AUTOSOMAL RECESSIVE OSTEOPETROSIS. | |
Lessa | Role of decellularized liver matrix on human embryonic stem cell differentiation into functional hepatocytes |