AU2004269361B2 - Method of in vitro differentiation of neural stem cells, motor neurons and dopamine neurons from primate embryonic stem cells - Google Patents
Method of in vitro differentiation of neural stem cells, motor neurons and dopamine neurons from primate embryonic stem cells Download PDFInfo
- Publication number
- AU2004269361B2 AU2004269361B2 AU2004269361A AU2004269361A AU2004269361B2 AU 2004269361 B2 AU2004269361 B2 AU 2004269361B2 AU 2004269361 A AU2004269361 A AU 2004269361A AU 2004269361 A AU2004269361 A AU 2004269361A AU 2004269361 B2 AU2004269361 B2 AU 2004269361B2
- Authority
- AU
- Australia
- Prior art keywords
- cells
- neurons
- population
- neural
- cell
- 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.)
- Expired
Links
- 210000002569 neuron Anatomy 0.000 title claims description 171
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 title claims description 132
- 238000000034 method Methods 0.000 title claims description 76
- 229960003638 dopamine Drugs 0.000 title claims description 66
- 210000002161 motor neuron Anatomy 0.000 title claims description 65
- 210000001671 embryonic stem cell Anatomy 0.000 title claims description 14
- 210000001178 neural stem cell Anatomy 0.000 title claims description 10
- 230000004069 differentiation Effects 0.000 title description 74
- 238000000338 in vitro Methods 0.000 title description 20
- 241000288906 Primates Species 0.000 title description 5
- 210000004027 cell Anatomy 0.000 claims description 529
- 230000001537 neural effect Effects 0.000 claims description 120
- 210000001259 mesencephalon Anatomy 0.000 claims description 61
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 claims description 59
- 102100035290 Fibroblast growth factor 13 Human genes 0.000 claims description 58
- 101100310657 Mus musculus Sox1 gene Proteins 0.000 claims description 58
- 210000002242 embryoid body Anatomy 0.000 claims description 31
- 238000011161 development Methods 0.000 claims description 30
- 230000018109 developmental process Effects 0.000 claims description 30
- 210000004129 prosencephalon Anatomy 0.000 claims description 27
- 101000576323 Homo sapiens Motor neuron and pancreas homeobox protein 1 Proteins 0.000 claims description 21
- 108010058699 Choline O-acetyltransferase Proteins 0.000 claims description 17
- 101150092239 OTX2 gene Proteins 0.000 claims description 13
- 101150004541 HOXC8 gene Proteins 0.000 claims description 12
- 238000012360 testing method Methods 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 11
- 238000012258 culturing Methods 0.000 claims description 9
- 239000003102 growth factor Substances 0.000 claims description 9
- 210000003061 neural cell Anatomy 0.000 claims description 9
- 230000001360 synchronised effect Effects 0.000 claims description 9
- 102100028072 Fibroblast growth factor 4 Human genes 0.000 claims description 7
- 101001060274 Homo sapiens Fibroblast growth factor 4 Proteins 0.000 claims description 7
- 108091006774 SLC18A3 Proteins 0.000 claims description 6
- 102100039452 Vesicular acetylcholine transporter Human genes 0.000 claims description 6
- 102100037665 Fibroblast growth factor 9 Human genes 0.000 claims description 5
- 101001027380 Homo sapiens Fibroblast growth factor 9 Proteins 0.000 claims description 5
- 101100451924 Mus musculus Hoxb6 gene Proteins 0.000 claims description 5
- 101100232284 Mus musculus Hoxc5 gene Proteins 0.000 claims description 5
- 102000007354 PAX6 Transcription Factor Human genes 0.000 claims description 5
- -1 Bfl Proteins 0.000 claims description 4
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 claims description 4
- 229960004373 acetylcholine Drugs 0.000 claims description 4
- 230000001902 propagating effect Effects 0.000 claims description 4
- 101100071843 Mus musculus Hoxb1 gene Proteins 0.000 claims description 3
- 102100037680 Fibroblast growth factor 8 Human genes 0.000 claims 5
- 101001027382 Homo sapiens Fibroblast growth factor 8 Proteins 0.000 claims 5
- 101150081664 PAX6 gene Proteins 0.000 claims 4
- 230000011712 cell development Effects 0.000 claims 3
- 102100038238 Aromatic-L-amino-acid decarboxylase Human genes 0.000 claims 2
- 101710151768 Aromatic-L-amino-acid decarboxylase Proteins 0.000 claims 2
- 101001123678 Homo sapiens Phenylethanolamine N-methyltransferase Proteins 0.000 claims 2
- 102100024611 Phosphatidylethanolamine N-methyltransferase Human genes 0.000 claims 2
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 claims 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 72
- 239000002243 precursor Substances 0.000 description 56
- 102000003693 Hedgehog Proteins Human genes 0.000 description 45
- 108090000031 Hedgehog Proteins Proteins 0.000 description 45
- 108091000117 Tyrosine 3-Monooxygenase Proteins 0.000 description 45
- 102000048218 Tyrosine 3-monooxygenases Human genes 0.000 description 45
- 239000002609 medium Substances 0.000 description 42
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 41
- 229930002330 retinoic acid Natural products 0.000 description 41
- 229960001727 tretinoin Drugs 0.000 description 41
- 102000003956 Fibroblast growth factor 8 Human genes 0.000 description 34
- 108090000368 Fibroblast growth factor 8 Proteins 0.000 description 34
- 241000699666 Mus <mouse, genus> Species 0.000 description 33
- 238000011282 treatment Methods 0.000 description 33
- 230000015572 biosynthetic process Effects 0.000 description 32
- 230000014509 gene expression Effects 0.000 description 26
- 238000005755 formation reaction Methods 0.000 description 25
- 210000004556 brain Anatomy 0.000 description 23
- 230000036982 action potential Effects 0.000 description 19
- 210000000276 neural tube Anatomy 0.000 description 19
- 210000002777 columnar cell Anatomy 0.000 description 18
- 210000000461 neuroepithelial cell Anatomy 0.000 description 18
- 101100285407 Mus musculus En1 gene Proteins 0.000 description 17
- 230000008569 process Effects 0.000 description 17
- 102100023460 Choline O-acetyltransferase Human genes 0.000 description 16
- 102000008730 Nestin Human genes 0.000 description 16
- 108010088225 Nestin Proteins 0.000 description 16
- 210000005055 nestin Anatomy 0.000 description 16
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 15
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 15
- 238000012744 immunostaining Methods 0.000 description 15
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 14
- 108091023040 Transcription factor Proteins 0.000 description 14
- 102000040945 Transcription factor Human genes 0.000 description 14
- 238000004458 analytical method Methods 0.000 description 14
- 108010007093 dispase Proteins 0.000 description 14
- 230000002269 spontaneous effect Effects 0.000 description 14
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 230000006698 induction Effects 0.000 description 12
- 239000003550 marker Substances 0.000 description 12
- 210000000278 spinal cord Anatomy 0.000 description 12
- 238000002474 experimental method Methods 0.000 description 11
- 238000001727 in vivo Methods 0.000 description 10
- 239000010410 layer Substances 0.000 description 10
- 210000004940 nucleus Anatomy 0.000 description 10
- QMGVPVSNSZLJIA-FVWCLLPLSA-N strychnine Chemical compound O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1 QMGVPVSNSZLJIA-FVWCLLPLSA-N 0.000 description 10
- 230000000946 synaptic effect Effects 0.000 description 10
- 238000002054 transplantation Methods 0.000 description 10
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 9
- 102100039289 Glial fibrillary acidic protein Human genes 0.000 description 9
- 101710193519 Glial fibrillary acidic protein Proteins 0.000 description 9
- 210000003050 axon Anatomy 0.000 description 9
- 210000005046 glial fibrillary acidic protein Anatomy 0.000 description 9
- 210000001176 projection neuron Anatomy 0.000 description 9
- 239000000758 substrate Substances 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- IYGYMKDQCDOMRE-QRWMCTBCSA-N Bicculine Chemical compound O([C@H]1C2C3=CC=4OCOC=4C=C3CCN2C)C(=O)C2=C1C=CC1=C2OCO1 IYGYMKDQCDOMRE-QRWMCTBCSA-N 0.000 description 8
- BAQMYDQNMFBZNA-UHFFFAOYSA-N N-biotinyl-L-lysine Natural products N1C(=O)NC2C(CCCCC(=O)NCCCCC(N)C(O)=O)SCC21 BAQMYDQNMFBZNA-UHFFFAOYSA-N 0.000 description 8
- 241000283973 Oryctolagus cuniculus Species 0.000 description 8
- BAQMYDQNMFBZNA-MNXVOIDGSA-N biocytin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)NCCCC[C@H](N)C(O)=O)SC[C@@H]21 BAQMYDQNMFBZNA-MNXVOIDGSA-N 0.000 description 8
- 238000010348 incorporation Methods 0.000 description 8
- 239000012981 Hank's balanced salt solution Substances 0.000 description 7
- 102000008763 Neurofilament Proteins Human genes 0.000 description 7
- 108010088373 Neurofilament Proteins Proteins 0.000 description 7
- 230000001464 adherent effect Effects 0.000 description 7
- 229960005070 ascorbic acid Drugs 0.000 description 7
- 235000010323 ascorbic acid Nutrition 0.000 description 7
- 239000011668 ascorbic acid Substances 0.000 description 7
- 102000014823 calbindin Human genes 0.000 description 7
- 108060001061 calbindin Proteins 0.000 description 7
- 210000003169 central nervous system Anatomy 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 238000002955 isolation Methods 0.000 description 7
- 230000003988 neural development Effects 0.000 description 7
- 210000005044 neurofilament Anatomy 0.000 description 7
- 230000004031 neuronal differentiation Effects 0.000 description 7
- 210000004248 oligodendroglia Anatomy 0.000 description 7
- 238000007747 plating Methods 0.000 description 7
- 238000003757 reverse transcription PCR Methods 0.000 description 7
- 102000034615 Glial cell line-derived neurotrophic factor Human genes 0.000 description 6
- 108091010837 Glial cell line-derived neurotrophic factor Proteins 0.000 description 6
- 101001053263 Homo sapiens Insulin gene enhancer protein ISL-1 Proteins 0.000 description 6
- 102100024392 Insulin gene enhancer protein ISL-1 Human genes 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 210000005056 cell body Anatomy 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 239000000306 component Substances 0.000 description 6
- 230000002999 depolarising effect Effects 0.000 description 6
- 230000002255 enzymatic effect Effects 0.000 description 6
- 230000002964 excitative effect Effects 0.000 description 6
- 229940050410 gluconate Drugs 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 210000001161 mammalian embryo Anatomy 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 5
- 102000004058 Leukemia inhibitory factor Human genes 0.000 description 5
- 108090000581 Leukemia inhibitory factor Proteins 0.000 description 5
- 108010002822 Phenylethanolamine N-Methyltransferase Proteins 0.000 description 5
- 102100028917 Phenylethanolamine N-methyltransferase Human genes 0.000 description 5
- 102100034026 RNA-binding protein Musashi homolog 1 Human genes 0.000 description 5
- 101710129077 RNA-binding protein Musashi homolog 1 Proteins 0.000 description 5
- 210000001130 astrocyte Anatomy 0.000 description 5
- 238000004113 cell culture Methods 0.000 description 5
- 210000004748 cultured cell Anatomy 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 210000002950 fibroblast Anatomy 0.000 description 5
- 229960002897 heparin Drugs 0.000 description 5
- 229920000669 heparin Polymers 0.000 description 5
- 210000001020 neural plate Anatomy 0.000 description 5
- 230000000644 propagated effect Effects 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 210000000130 stem cell Anatomy 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 5
- IAWXTSMHXFRLQR-UHFFFAOYSA-N 2,3-bis($l^{1}-oxidanyl)-7-nitroquinoxaline-6-carbonitrile Chemical compound O=C1C(=O)N=C2C=C(C#N)C([N+](=O)[O-])=CC2=N1 IAWXTSMHXFRLQR-UHFFFAOYSA-N 0.000 description 4
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 4
- 101800003838 Epidermal growth factor Proteins 0.000 description 4
- 108700005087 Homeobox Genes Proteins 0.000 description 4
- 108010048671 Homeodomain Proteins Proteins 0.000 description 4
- 102000009331 Homeodomain Proteins Human genes 0.000 description 4
- 101100074807 Mus musculus Lhx3 gene Proteins 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- QMGVPVSNSZLJIA-UHFFFAOYSA-N Nux Vomica Natural products C1C2C3C4N(C=5C6=CC=CC=5)C(=O)CC3OCC=C2CN2C1C46CC2 QMGVPVSNSZLJIA-UHFFFAOYSA-N 0.000 description 4
- 229930040373 Paraformaldehyde Natural products 0.000 description 4
- 208000018737 Parkinson disease Diseases 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 241000283984 Rodentia Species 0.000 description 4
- 108010087230 Sincalide Proteins 0.000 description 4
- 241001279009 Strychnos toxifera Species 0.000 description 4
- 102000001435 Synapsin Human genes 0.000 description 4
- 108050009621 Synapsin Proteins 0.000 description 4
- 238000004115 adherent culture Methods 0.000 description 4
- 239000000427 antigen Substances 0.000 description 4
- AACMFFIUYXGCOC-UHFFFAOYSA-N bicuculline Natural products CN1CCc2cc3OCOc3cc2C1C4OCc5c6OCOc6ccc45 AACMFFIUYXGCOC-UHFFFAOYSA-N 0.000 description 4
- 210000003855 cell nucleus Anatomy 0.000 description 4
- 238000012512 characterization method Methods 0.000 description 4
- IYGYMKDQCDOMRE-UHFFFAOYSA-N d-Bicucullin Natural products CN1CCC2=CC=3OCOC=3C=C2C1C1OC(=O)C2=C1C=CC1=C2OCO1 IYGYMKDQCDOMRE-UHFFFAOYSA-N 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 229940116977 epidermal growth factor Drugs 0.000 description 4
- 239000000835 fiber Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 210000005260 human cell Anatomy 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 238000002372 labelling Methods 0.000 description 4
- 239000013642 negative control Substances 0.000 description 4
- 210000002241 neurite Anatomy 0.000 description 4
- 210000004498 neuroglial cell Anatomy 0.000 description 4
- 210000000956 olfactory bulb Anatomy 0.000 description 4
- 229920002866 paraformaldehyde Polymers 0.000 description 4
- 108010057417 polysialyl neural cell adhesion molecule Proteins 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)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](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 4
- 229960005453 strychnine Drugs 0.000 description 4
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 3
- WOVKYSAHUYNSMH-UHFFFAOYSA-N BROMODEOXYURIDINE Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-UHFFFAOYSA-N 0.000 description 3
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 3
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 3
- 108010078791 Carrier Proteins Proteins 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- 108700014808 Homeobox Protein Nkx-2.2 Proteins 0.000 description 3
- 101000979001 Homo sapiens Methionine aminopeptidase 2 Proteins 0.000 description 3
- 101000969087 Homo sapiens Microtubule-associated protein 2 Proteins 0.000 description 3
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 102100023174 Methionine aminopeptidase 2 Human genes 0.000 description 3
- 102000019040 Nuclear Antigens Human genes 0.000 description 3
- 108010051791 Nuclear Antigens Proteins 0.000 description 3
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 3
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 3
- 102000000813 Proto-Oncogene Proteins c-ret Human genes 0.000 description 3
- 108010001648 Proto-Oncogene Proteins c-ret Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 102000004874 Synaptophysin Human genes 0.000 description 3
- 108090001076 Synaptophysin Proteins 0.000 description 3
- 102000004142 Trypsin Human genes 0.000 description 3
- 108090000631 Trypsin Proteins 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 210000002459 blastocyst Anatomy 0.000 description 3
- 210000005013 brain tissue Anatomy 0.000 description 3
- 229950004398 broxuridine Drugs 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 210000005064 dopaminergic neuron Anatomy 0.000 description 3
- 239000003797 essential amino acid Substances 0.000 description 3
- 235000020776 essential amino acid Nutrition 0.000 description 3
- 230000000763 evoking effect Effects 0.000 description 3
- 230000001747 exhibiting effect Effects 0.000 description 3
- 230000001605 fetal effect Effects 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 210000001320 hippocampus Anatomy 0.000 description 3
- 210000004408 hybridoma Anatomy 0.000 description 3
- 210000003016 hypothalamus Anatomy 0.000 description 3
- 238000007901 in situ hybridization Methods 0.000 description 3
- 210000003078 multipolar neuron Anatomy 0.000 description 3
- 239000002858 neurotransmitter agent Substances 0.000 description 3
- 230000002474 noradrenergic effect Effects 0.000 description 3
- 229960002748 norepinephrine Drugs 0.000 description 3
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 3
- 229960003104 ornithine Drugs 0.000 description 3
- 108010017843 platelet-derived growth factor A Proteins 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 230000008439 repair process Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 230000036390 resting membrane potential Effects 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 210000003523 substantia nigra Anatomy 0.000 description 3
- 210000000225 synapse Anatomy 0.000 description 3
- CFMYXEVWODSLAX-QOZOJKKESA-N tetrodotoxin Chemical compound O([C@@]([C@H]1O)(O)O[C@H]2[C@@]3(O)CO)[C@H]3[C@@H](O)[C@]11[C@H]2[C@@H](O)N=C(N)N1 CFMYXEVWODSLAX-QOZOJKKESA-N 0.000 description 3
- 229950010357 tetrodotoxin Drugs 0.000 description 3
- CFMYXEVWODSLAX-UHFFFAOYSA-N tetrodotoxin Natural products C12C(O)NC(=N)NC2(C2O)C(O)C3C(CO)(O)C1OC2(O)O3 CFMYXEVWODSLAX-UHFFFAOYSA-N 0.000 description 3
- 229950003937 tolonium Drugs 0.000 description 3
- HNONEKILPDHFOL-UHFFFAOYSA-M tolonium chloride Chemical compound [Cl-].C1=C(C)C(N)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 HNONEKILPDHFOL-UHFFFAOYSA-M 0.000 description 3
- 230000002110 toxicologic effect Effects 0.000 description 3
- 231100000027 toxicology Toxicity 0.000 description 3
- 239000012588 trypsin Substances 0.000 description 3
- 210000004515 ventral tegmental area Anatomy 0.000 description 3
- VOROEQBFPPIACJ-SCSAIBSYSA-N (2r)-2-amino-5-phosphonopentanoic acid Chemical compound OC(=O)[C@H](N)CCCP(O)(O)=O VOROEQBFPPIACJ-SCSAIBSYSA-N 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- 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 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 241001076388 Fimbria Species 0.000 description 2
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 2
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- 238000012897 Levenberg–Marquardt algorithm Methods 0.000 description 2
- 239000012580 N-2 Supplement Substances 0.000 description 2
- 102100035423 POU domain, class 5, transcription factor 1 Human genes 0.000 description 2
- 101710126211 POU domain, class 5, transcription factor 1 Proteins 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000000692 Student's t-test Methods 0.000 description 2
- 206010043276 Teratoma Diseases 0.000 description 2
- 102000000307 Transcription factor SOX-1 Human genes 0.000 description 2
- 108050008750 Transcription factor SOX-1 Proteins 0.000 description 2
- 102000004243 Tubulin Human genes 0.000 description 2
- 108090000704 Tubulin Proteins 0.000 description 2
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 210000000133 brain stem Anatomy 0.000 description 2
- 235000010633 broth Nutrition 0.000 description 2
- 238000004422 calculation algorithm Methods 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000004186 co-expression Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 210000000877 corpus callosum Anatomy 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 210000001654 germ layer Anatomy 0.000 description 2
- 229930195712 glutamate Natural products 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 2
- 210000004884 grey matter Anatomy 0.000 description 2
- 230000000971 hippocampal effect Effects 0.000 description 2
- 238000003365 immunocytochemistry Methods 0.000 description 2
- 238000010166 immunofluorescence Methods 0.000 description 2
- 238000002991 immunohistochemical analysis 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
- 210000001153 interneuron Anatomy 0.000 description 2
- 238000007914 intraventricular administration Methods 0.000 description 2
- 210000003140 lateral ventricle Anatomy 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000028161 membrane depolarization Effects 0.000 description 2
- 239000003068 molecular probe Substances 0.000 description 2
- 208000005264 motor neuron disease Diseases 0.000 description 2
- 210000001577 neostriatum Anatomy 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 230000004766 neurogenesis Effects 0.000 description 2
- 230000014511 neuron projection development Effects 0.000 description 2
- 229920002338 polyhydroxyethylmethacrylate Polymers 0.000 description 2
- 230000001242 postsynaptic effect Effects 0.000 description 2
- 230000035935 pregnancy Effects 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- KIDHWZJUCRJVML-UHFFFAOYSA-N putrescine Chemical compound NCCCCN KIDHWZJUCRJVML-UHFFFAOYSA-N 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000007261 regionalization Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 210000001082 somatic cell Anatomy 0.000 description 2
- 208000020431 spinal cord injury Diseases 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 238000004114 suspension culture Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000005062 synaptic transmission Effects 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- 210000004885 white matter Anatomy 0.000 description 2
- 239000002023 wood Substances 0.000 description 2
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- PRDFBSVERLRRMY-UHFFFAOYSA-N 2'-(4-ethoxyphenyl)-5-(4-methylpiperazin-1-yl)-2,5'-bibenzimidazole Chemical compound C1=CC(OCC)=CC=C1C1=NC2=CC=C(C=3NC4=CC(=CC=C4N=3)N3CCN(C)CC3)C=C2N1 PRDFBSVERLRRMY-UHFFFAOYSA-N 0.000 description 1
- 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 1
- RPXVIAFEQBNEAX-UHFFFAOYSA-N 6-Cyano-7-nitroquinoxaline-2,3-dione Chemical compound N1C(=O)C(=O)NC2=C1C=C([N+](=O)[O-])C(C#N)=C2 RPXVIAFEQBNEAX-UHFFFAOYSA-N 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 108091023043 Alu Element Proteins 0.000 description 1
- 241000269350 Anura Species 0.000 description 1
- FTEDXVNDVHYDQW-UHFFFAOYSA-N BAPTA Chemical compound OC(=O)CN(CC(O)=O)C1=CC=CC=C1OCCOC1=CC=CC=C1N(CC(O)=O)CC(O)=O FTEDXVNDVHYDQW-UHFFFAOYSA-N 0.000 description 1
- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 1
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 241000284156 Clerodendrum quadriloculare Species 0.000 description 1
- 229930105110 Cyclosporin A Natural products 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
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 241000252212 Danio rerio Species 0.000 description 1
- 102000007260 Deoxyribonuclease I Human genes 0.000 description 1
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 1
- SHIBSTMRCDJXLN-UHFFFAOYSA-N Digoxigenin Natural products C1CC(C2C(C3(C)CCC(O)CC3CC2)CC2O)(O)C2(C)C1C1=CC(=O)OC1 SHIBSTMRCDJXLN-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000900767 Homo sapiens Protein cornichon homolog 1 Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-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
- 241000282560 Macaca mulatta Species 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 102000008109 Mixed Function Oxygenases Human genes 0.000 description 1
- 108010074633 Mixed Function Oxygenases Proteins 0.000 description 1
- 101100518992 Mus musculus Pax2 gene Proteins 0.000 description 1
- 108010083674 Myelin Proteins Proteins 0.000 description 1
- 102000006386 Myelin Proteins Human genes 0.000 description 1
- 101150026563 NR4A2 gene Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 102100021852 Neuronal cell adhesion molecule Human genes 0.000 description 1
- 101710130688 Neuronal cell adhesion molecule Proteins 0.000 description 1
- 108010032788 PAX6 Transcription Factor Proteins 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 102100022049 Protein cornichon homolog 1 Human genes 0.000 description 1
- 239000005700 Putrescine Substances 0.000 description 1
- 101100184491 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) MNR2 gene Proteins 0.000 description 1
- 108010052164 Sodium Channels Proteins 0.000 description 1
- 102000018674 Sodium Channels Human genes 0.000 description 1
- 108010006785 Taq Polymerase Proteins 0.000 description 1
- 102000004338 Transferrin Human genes 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- 108010020033 Vesicular Monoamine Transport Proteins Proteins 0.000 description 1
- 102000009659 Vesicular Monoamine Transport Proteins Human genes 0.000 description 1
- 102000016913 Voltage-Gated Sodium Channels Human genes 0.000 description 1
- 108010053752 Voltage-Gated Sodium Channels Proteins 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 210000002934 adrenergic neuron Anatomy 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 229940112869 bone morphogenetic protein Drugs 0.000 description 1
- 230000004641 brain development Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 210000004413 cardiac myocyte Anatomy 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 230000007248 cellular mechanism Effects 0.000 description 1
- 210000004289 cerebral ventricle Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 230000008045 co-localization Effects 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 230000003750 conditioning effect Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000011461 current therapy Methods 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 210000001787 dendrite Anatomy 0.000 description 1
- 230000002074 deregulated effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- QONQRTHLHBTMGP-UHFFFAOYSA-N digitoxigenin Natural products CC12CCC(C3(CCC(O)CC3CC3)C)C3C11OC1CC2C1=CC(=O)OC1 QONQRTHLHBTMGP-UHFFFAOYSA-N 0.000 description 1
- SHIBSTMRCDJXLN-KCZCNTNESA-N digoxigenin Chemical compound C1([C@@H]2[C@@]3([C@@](CC2)(O)[C@H]2[C@@H]([C@@]4(C)CC[C@H](O)C[C@H]4CC2)C[C@H]3O)C)=CC(=O)OC1 SHIBSTMRCDJXLN-KCZCNTNESA-N 0.000 description 1
- MHUWZNTUIIFHAS-CLFAGFIQSA-N dioleoyl phosphatidic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(COP(O)(O)=O)OC(=O)CCCCCCC\C=C/CCCCCCCC MHUWZNTUIIFHAS-CLFAGFIQSA-N 0.000 description 1
- BVTBRVFYZUCAKH-UHFFFAOYSA-L disodium selenite Chemical compound [Na+].[Na+].[O-][Se]([O-])=O BVTBRVFYZUCAKH-UHFFFAOYSA-L 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 230000028436 dopamine uptake Effects 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000007877 drug screening Methods 0.000 description 1
- 210000003981 ectoderm Anatomy 0.000 description 1
- 230000007831 electrophysiology Effects 0.000 description 1
- 238000002001 electrophysiology Methods 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 210000001900 endoderm Anatomy 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 210000003754 fetus Anatomy 0.000 description 1
- 238000010304 firing Methods 0.000 description 1
- 239000000834 fixative Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000000848 glutamatergic effect Effects 0.000 description 1
- 210000000020 growth cone Anatomy 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 230000001744 histochemical effect Effects 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000010185 immunofluorescence analysis Methods 0.000 description 1
- 238000013115 immunohistochemical detection Methods 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 210000002660 insulin-secreting cell Anatomy 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 210000002425 internal capsule Anatomy 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000000185 intracerebroventricular administration Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 229960004502 levodopa Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 210000005171 mammalian brain Anatomy 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000012533 medium component Substances 0.000 description 1
- 210000003716 mesoderm Anatomy 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 238000012895 mono-exponential function Methods 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 230000006740 morphological transformation Effects 0.000 description 1
- 230000008271 nervous system development Effects 0.000 description 1
- 210000005155 neural progenitor cell Anatomy 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 101710135378 pH 6 antigen Proteins 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 238000000059 patterning Methods 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000000088 plastic resin Substances 0.000 description 1
- 108010055896 polyornithine Proteins 0.000 description 1
- 229920002714 polyornithine Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000009696 proliferative response Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 150000003385 sodium Chemical class 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229960001471 sodium selenite Drugs 0.000 description 1
- 239000011781 sodium selenite Substances 0.000 description 1
- 235000015921 sodium selenite Nutrition 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000009168 stem cell therapy Methods 0.000 description 1
- 238000009580 stem-cell therapy Methods 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 210000001103 thalamus Anatomy 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 210000002993 trophoblast Anatomy 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
- 230000000007 visual effect Effects 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
- C12N5/0618—Cells of the nervous system
- C12N5/0619—Neurons
-
- 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
- C12N5/0618—Cells of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- C12N5/0603—Embryonic cells ; Embryoid bodies
- C12N5/0606—Pluripotent embryonic cells, e.g. embryonic stem cells [ES]
-
- 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
- C12N5/0618—Cells of the nervous system
- C12N5/0623—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
- C12N2500/00—Specific components of cell culture medium
- C12N2500/05—Inorganic components
- C12N2500/10—Metals; Metal chelators
- C12N2500/20—Transition metals
- C12N2500/24—Iron; Fe chelators; Transferrin
- C12N2500/25—Insulin-transferrin; Insulin-transferrin-selenium
-
- 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
- C12N2500/30—Organic components
- C12N2500/44—Thiols, e.g. mercaptoethanol
-
- 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
- C12N2500/30—Organic components
- C12N2500/46—Amines, e.g. putrescine
-
- 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
- C12N2501/13—Nerve growth factor [NGF]; Brain-derived neurotrophic factor [BDNF]; Cilliary neurotrophic factor [CNTF]; Glial-derived neurotrophic factor [GDNF]; Neurotrophins [NT]; Neuregulins
-
- 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
- C12N2501/30—Hormones
- C12N2501/38—Hormones with nuclear receptors
- C12N2501/385—Hormones with nuclear receptors of the family of the retinoic acid recptor, e.g. RAR, RXR; Peroxisome proliferator-activated receptor [PPAR]
-
- 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
- C12N2501/90—Polysaccharides
- C12N2501/91—Heparin
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2506/00—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells
- C12N2506/02—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from embryonic cells
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- General Health & Medical Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Developmental Biology & Embryology (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Reproductive Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Gynecology & Obstetrics (AREA)
- Psychology (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)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US49883103P | 2003-08-29 | 2003-08-29 | |
| US60/498,831 | 2003-08-29 | ||
| US49957003P | 2003-09-02 | 2003-09-02 | |
| US60/499,570 | 2003-09-02 | ||
| PCT/US2004/027841 WO2005021720A2 (fr) | 2003-08-29 | 2004-08-27 | Procede de differentiation in vitro de cellules souches neuronales, de neurones moteurs et de neurones de dopamine provenant de cellules souches embryonnaires de primates |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2004269361A1 AU2004269361A1 (en) | 2005-03-10 |
| AU2004269361B2 true AU2004269361B2 (en) | 2010-05-20 |
Family
ID=34278616
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2004269361A Expired AU2004269361B2 (en) | 2003-08-29 | 2004-08-27 | Method of in vitro differentiation of neural stem cells, motor neurons and dopamine neurons from primate embryonic stem cells |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP1670901A4 (fr) |
| JP (2) | JP2007503811A (fr) |
| KR (2) | KR20080109943A (fr) |
| AU (1) | AU2004269361B2 (fr) |
| CA (1) | CA2536588C (fr) |
| GB (1) | GB2421029B (fr) |
| IL (2) | IL173832A (fr) |
| WO (1) | WO2005021720A2 (fr) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8153424B2 (en) | 2001-10-03 | 2012-04-10 | Wisconsin Alumni Research Foundation | Method of in vitro differentiation of neural stem cells, motor neurons and dopamine neurons from primate embryonic stem cells |
| US7588937B2 (en) | 2001-10-03 | 2009-09-15 | Wisconsin Alumni Research Foundation | Method of in vitro differentiation of neural stem cells, motor neurons and dopamine neurons from primate embryonic stem cells |
| US7632679B2 (en) * | 2002-07-16 | 2009-12-15 | The Trustees Of Columbia University In The City Of New York | Systems and methods for screening for modulators of neural differentiation |
| JP4792290B2 (ja) * | 2005-12-27 | 2011-10-12 | 財団法人 東京都医学総合研究所 | 神経幹細胞の製造方法 |
| EA027648B9 (ru) | 2006-03-07 | 2018-01-31 | Гита Шроф | КОМПОЗИЦИИ, СОДЕРЖАЩИЕ ЭМБРИОНАЛЬНЫЕ СТВОЛОВЫЕ КЛЕТКИ ЧЕЛОВЕКА (ЭСКч) ИЛИ КЛЕТКИ-ПРОИЗВОДНЫЕ ЭСКч, И ИХ ПРИМЕНЕНИЕ |
| KR100838013B1 (ko) * | 2006-06-07 | 2008-06-12 | 제일약품주식회사 | 인간배아줄기세포로부터 단계적 선별법을 통해 고수율로신경전구세포, 신경세포 및 기능성 도파민신경세포를생성하는 방법 |
| CA2721952C (fr) | 2008-04-22 | 2019-11-12 | Regenerative Research Foundation | Cellules souches de l'epithelium pigmentaire retinien |
| KR101168053B1 (ko) * | 2009-11-06 | 2012-07-24 | 연세대학교 산학협력단 | 효율적이고 보편적인 전분화능 줄기세포의 신경세포 분화 유도방법 |
| CN103052707A (zh) | 2010-07-30 | 2013-04-17 | 剑桥实业有限公司 | 人类多能细胞的皮层生成 |
| US9487752B2 (en) | 2011-03-30 | 2016-11-08 | Cellular Dynamics International, Inc. | Priming of pluripotent stem cells for neural differentiation |
| JP6015112B2 (ja) * | 2012-05-11 | 2016-10-26 | 株式会社ニコン | 細胞評価装置、細胞評価方法およびプログラム |
| MA67580B1 (fr) * | 2015-11-12 | 2024-09-30 | F. Hoffmann-La Roche Ag | Oligonucléotides pour induire l'expression de paternal ube3a |
| WO2017123806A1 (fr) | 2016-01-12 | 2017-07-20 | Cedars-Sinai Medical Center | Procédé de suivi non destructeur de processus biologiques dans des systèmes de culture de tissu microfluidiques |
| WO2017136479A1 (fr) | 2016-02-01 | 2017-08-10 | Cedars-Sinai Medical Center | Systèmes et procédés de mise en croissance de cellules intestinales dans des dispositifs microfluidiques |
| JPWO2017209290A1 (ja) * | 2016-06-03 | 2019-04-11 | 国立大学法人京都大学 | 多能性幹細胞由来運動ニューロンの製造及びその用途 |
| JP6376196B2 (ja) * | 2016-09-29 | 2018-08-22 | 株式会社ニコン | 細胞評価装置、細胞評価方法およびプログラム |
| WO2018140647A1 (fr) | 2017-01-25 | 2018-08-02 | Cedars-Sinai Medical Center | Induction in vitro de différenciation de type mammaire à partir de cellules souches pluripotentes humaines |
| US11767513B2 (en) | 2017-03-14 | 2023-09-26 | Cedars-Sinai Medical Center | Neuromuscular junction |
| WO2018176001A2 (fr) | 2017-03-24 | 2018-09-27 | Cedars-Sinai Medical Center | Procédés et compositions pour la production d'épithélium de trompes de fallope |
| CN108048399B (zh) * | 2017-11-13 | 2021-03-23 | 昆明医科大学 | 一种meth诱导树鼩多巴胺神经元原代细胞自噬的方法 |
| JP2019106895A (ja) * | 2017-12-15 | 2019-07-04 | インダストリー‐ユニバーシティー コーぺレーション ファンデーション ハンヤン ユニバーシティ | 神経幹細胞または神経前駆細胞からドーパミン神経細胞への分化方法 |
| EP3768823A4 (fr) | 2018-03-23 | 2022-03-09 | Cedars-Sinai Medical Center | Procédés d'utilisation de cellules des îlots pancréatiques |
| US11981918B2 (en) | 2018-04-06 | 2024-05-14 | Cedars-Sinai Medical Center | Differentiation technique to generate dopaminergic neurons from induced pluripotent stem cells |
| US12241085B2 (en) | 2018-04-06 | 2025-03-04 | Cedars-Sinai Medical Center | Human pluripotent stem cell derived neurodegenerative disease models on a microfluidic chip |
| JP2021532736A (ja) * | 2018-06-06 | 2021-12-02 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニアThe Regents Of The University Of California | 神経幹細胞組成物および神経変性障害を処置するための方法 |
| JP6798533B2 (ja) * | 2018-07-26 | 2020-12-09 | 株式会社ニコン | 細胞評価装置、インキュベータおよびプログラム |
| CN114375328B (zh) * | 2019-09-06 | 2024-12-27 | 学校法人庆应义塾 | 包含胶质前体细胞的细胞聚集体的制备方法 |
| WO2022098895A1 (fr) * | 2020-11-04 | 2022-05-12 | The Regents Of The University Of Michigan | Dispositifs microfluidiques et procédés de développement de tissus du type tube neural ou sphéroïdes neuraux |
| JP7235027B2 (ja) * | 2020-11-16 | 2023-03-08 | 株式会社ニコン | 細胞評価装置、インキュベータおよびプログラム |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020009743A1 (en) * | 2000-05-17 | 2002-01-24 | Carpenter Melissa K. | Neural progenitor cell populations |
| US20020168763A1 (en) * | 2000-11-30 | 2002-11-14 | Yan Wen Liang | Isolated homozygous stem cells, differentiated cells derived therefrom, and materials and methods for making and using same |
| US20030068819A1 (en) * | 2001-10-03 | 2003-04-10 | Su-Chun Zhang | Method of in vitro differentiation of transplantatable neural precursor cells from primate embryonic stem cells |
| US20030211605A1 (en) * | 2001-05-01 | 2003-11-13 | Lee Sang-Hun | Derivation of midbrain dopaminergic neurons from embryonic stem cells |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7144997B2 (en) * | 1997-07-24 | 2006-12-05 | Curis, Inc. | Vertebrate embryonic patterning-inducing proteins, compositions and uses related therto |
| CA2298506A1 (fr) * | 1997-08-04 | 1999-02-11 | The Regents Of The University Of California | Procede de traitement des deficits neurologiques |
| AU2001259323A1 (en) * | 2000-05-01 | 2001-11-12 | Sang-Hun Lee | Derivation of midbrain dopaminergic neurons from embryonic stem cells |
-
2004
- 2004-08-27 GB GB0605851A patent/GB2421029B/en not_active Expired - Lifetime
- 2004-08-27 WO PCT/US2004/027841 patent/WO2005021720A2/fr not_active Ceased
- 2004-08-27 KR KR1020087028900A patent/KR20080109943A/ko not_active Ceased
- 2004-08-27 AU AU2004269361A patent/AU2004269361B2/en not_active Expired
- 2004-08-27 JP JP2006524872A patent/JP2007503811A/ja not_active Withdrawn
- 2004-08-27 CA CA2536588A patent/CA2536588C/fr not_active Expired - Lifetime
- 2004-08-27 KR KR1020067004226A patent/KR20060115351A/ko not_active Ceased
- 2004-08-27 EP EP04782339A patent/EP1670901A4/fr not_active Withdrawn
-
2006
- 2006-02-20 IL IL173832A patent/IL173832A/en active IP Right Grant
-
2009
- 2009-04-28 IL IL198450A patent/IL198450A/en active IP Right Grant
-
2010
- 2010-01-28 JP JP2010017013A patent/JP5529561B2/ja not_active Expired - Lifetime
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020009743A1 (en) * | 2000-05-17 | 2002-01-24 | Carpenter Melissa K. | Neural progenitor cell populations |
| US20020168763A1 (en) * | 2000-11-30 | 2002-11-14 | Yan Wen Liang | Isolated homozygous stem cells, differentiated cells derived therefrom, and materials and methods for making and using same |
| US20030211605A1 (en) * | 2001-05-01 | 2003-11-13 | Lee Sang-Hun | Derivation of midbrain dopaminergic neurons from embryonic stem cells |
| US20030068819A1 (en) * | 2001-10-03 | 2003-04-10 | Su-Chun Zhang | Method of in vitro differentiation of transplantatable neural precursor cells from primate embryonic stem cells |
Non-Patent Citations (2)
| Title |
|---|
| MUJTABA et al. Developmental Biology, 1999, vol. 214, no. 1, pages 113-127 * |
| ZHANG et al. Nature Biotechnology, 2001, vol. 19, no.12, pages 1129-1133 * |
Also Published As
| Publication number | Publication date |
|---|---|
| IL173832A (en) | 2011-02-28 |
| CA2536588A1 (fr) | 2005-03-10 |
| GB2421029B (en) | 2008-04-09 |
| KR20080109943A (ko) | 2008-12-17 |
| AU2004269361A1 (en) | 2005-03-10 |
| CA2536588C (fr) | 2018-04-24 |
| EP1670901A2 (fr) | 2006-06-21 |
| IL198450A (en) | 2011-01-31 |
| GB0605851D0 (en) | 2006-05-03 |
| GB2421029A (en) | 2006-06-14 |
| WO2005021720A2 (fr) | 2005-03-10 |
| WO2005021720A3 (fr) | 2005-05-19 |
| JP2007503811A (ja) | 2007-03-01 |
| EP1670901A4 (fr) | 2007-09-05 |
| KR20060115351A (ko) | 2006-11-08 |
| IL173832A0 (en) | 2006-07-05 |
| JP5529561B2 (ja) | 2014-06-25 |
| JP2010162024A (ja) | 2010-07-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2004269361B2 (en) | Method of in vitro differentiation of neural stem cells, motor neurons and dopamine neurons from primate embryonic stem cells | |
| Li | Zhang, l | |
| US8153424B2 (en) | Method of in vitro differentiation of neural stem cells, motor neurons and dopamine neurons from primate embryonic stem cells | |
| US9080151B2 (en) | Method of in vitro differentiation of neural stem cells, motor neurons and dopamine neurons from primate embryonic stem cells | |
| US6887706B2 (en) | Method of in vitro differentiation of transplantable neural precursor cells from primate embryonic stem cells | |
| US8133730B2 (en) | Generation of neural stem cells from undifferentiated human embryonic stem cells | |
| WO2009024448A1 (fr) | Génération de cellules neuronales à partir de cellules souches pluripotentes | |
| JP2024513912A (ja) | ドーパミン作動性前駆細胞(precursor cell)及び使用方法 | |
| EP1179046B1 (fr) | Cellules precurseurs a restriction de lignage, isolees a partir du tube neural de souris et de cellules souches embryonnaires de souris | |
| US10160951B2 (en) | Stem cells from the mammalian neural plate | |
| AU2003229132B2 (en) | Generation of neural stem cells from undifferentiated human embryonic stem cells | |
| HK1161298A (en) | Stem cells | |
| HK1158679A (en) | Stem cells | |
| AU4826200A (en) | Lineage-restricted precursor cells isolated from mouse neural tube and mouse embryonic stem cells |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| DA3 | Amendments made section 104 |
Free format text: THE NATURE OF THE AMENDMENT IS: DELETE CO-INVENTORS THOMSON, JAMES A; DUNCAN, IAN DAVID |
|
| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |