CA2870466A1 - Ocular therapeutics using embryonic stem cell microvesicles - Google Patents
Ocular therapeutics using embryonic stem cell microvesicles Download PDFInfo
- Publication number
- CA2870466A1 CA2870466A1 CA2870466A CA2870466A CA2870466A1 CA 2870466 A1 CA2870466 A1 CA 2870466A1 CA 2870466 A CA2870466 A CA 2870466A CA 2870466 A CA2870466 A CA 2870466A CA 2870466 A1 CA2870466 A1 CA 2870466A1
- Authority
- CA
- Canada
- Prior art keywords
- cells
- esmv
- retinal
- muller
- fraction
- 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.)
- Abandoned
Links
- 210000001671 embryonic stem cell Anatomy 0.000 title claims abstract description 55
- 239000003814 drug Substances 0.000 title description 7
- 230000002207 retinal effect Effects 0.000 claims abstract description 55
- 238000000034 method Methods 0.000 claims abstract description 31
- 210000000130 stem cell Anatomy 0.000 claims abstract description 23
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 19
- 230000007170 pathology Effects 0.000 claims abstract description 13
- 239000000203 mixture Substances 0.000 claims abstract description 11
- 210000003061 neural cell Anatomy 0.000 claims abstract description 7
- 210000004027 cell Anatomy 0.000 claims description 235
- 238000002347 injection Methods 0.000 claims description 35
- 239000007924 injection Substances 0.000 claims description 35
- 210000001164 retinal progenitor cell Anatomy 0.000 claims description 17
- 101150014889 Gad1 gene Proteins 0.000 claims description 11
- 208000002780 macular degeneration Diseases 0.000 claims description 11
- 230000002025 microglial effect Effects 0.000 claims description 11
- 108091008695 photoreceptors Proteins 0.000 claims description 11
- 208000022873 Ocular disease Diseases 0.000 claims description 10
- 108010010469 Qa-SNARE Proteins Proteins 0.000 claims description 10
- 102000001301 EGF receptor Human genes 0.000 claims description 9
- 108060006698 EGF receptor Proteins 0.000 claims description 9
- 206010064930 age-related macular degeneration Diseases 0.000 claims description 9
- 208000003556 Dry Eye Syndromes Diseases 0.000 claims description 8
- 201000007737 Retinal degeneration Diseases 0.000 claims description 8
- 230000003247 decreasing effect Effects 0.000 claims description 8
- 210000005155 neural progenitor cell Anatomy 0.000 claims description 8
- 230000004258 retinal degeneration Effects 0.000 claims description 8
- 206010013774 Dry eye Diseases 0.000 claims description 7
- 208000010412 Glaucoma Diseases 0.000 claims description 7
- 101001092197 Homo sapiens RNA binding protein fox-1 homolog 3 Proteins 0.000 claims description 7
- 102100035530 RNA binding protein fox-1 homolog 3 Human genes 0.000 claims description 7
- 102000005396 glutamine synthetase Human genes 0.000 claims description 7
- 108020002326 glutamine synthetase Proteins 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 6
- 101150008375 Pou4f1 gene Proteins 0.000 claims description 5
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 4
- 206010064996 Ulcerative keratitis Diseases 0.000 claims description 4
- 206010046851 Uveitis Diseases 0.000 claims description 4
- 230000024245 cell differentiation Effects 0.000 claims description 4
- 230000007850 degeneration Effects 0.000 claims description 4
- 208000009299 Benign Mucous Membrane Pemphigoid Diseases 0.000 claims description 3
- 208000007014 Retinitis pigmentosa Diseases 0.000 claims description 3
- 201000007717 corneal ulcer Diseases 0.000 claims description 3
- 230000003211 malignant effect Effects 0.000 claims description 3
- 208000015200 ocular cicatricial pemphigoid Diseases 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- 206010061323 Optic neuropathy Diseases 0.000 claims description 2
- 230000004340 degenerative myopia Effects 0.000 claims description 2
- 208000020911 optic nerve disease Diseases 0.000 claims description 2
- 238000011200 topical administration Methods 0.000 claims description 2
- 230000000699 topical effect Effects 0.000 claims description 2
- 102000015799 Qa-SNARE Proteins Human genes 0.000 claims 1
- 238000011282 treatment Methods 0.000 abstract description 74
- 239000002679 microRNA Substances 0.000 description 86
- 108091070501 miRNA Proteins 0.000 description 82
- 108090000623 proteins and genes Proteins 0.000 description 82
- 230000014509 gene expression Effects 0.000 description 73
- 210000001508 eye Anatomy 0.000 description 49
- 108020004999 messenger RNA Proteins 0.000 description 43
- 210000001525 retina Anatomy 0.000 description 36
- 241000699666 Mus <mouse, genus> Species 0.000 description 32
- 238000011529 RT qPCR Methods 0.000 description 29
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 27
- 230000001105 regulatory effect Effects 0.000 description 25
- 230000008859 change Effects 0.000 description 19
- 230000008929 regeneration Effects 0.000 description 17
- 238000011069 regeneration method Methods 0.000 description 17
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 16
- 239000003550 marker Substances 0.000 description 16
- 239000002609 medium Substances 0.000 description 16
- 239000002953 phosphate buffered saline Substances 0.000 description 16
- 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 15
- 238000004458 analytical method Methods 0.000 description 15
- WOVKYSAHUYNSMH-UHFFFAOYSA-N BROMODEOXYURIDINE Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-UHFFFAOYSA-N 0.000 description 14
- 101001010792 Homo sapiens Transcriptional regulator ERG Proteins 0.000 description 14
- 229950004398 broxuridine Drugs 0.000 description 14
- 238000002571 electroretinography Methods 0.000 description 14
- 238000002493 microarray Methods 0.000 description 14
- 238000012546 transfer Methods 0.000 description 14
- 241000699670 Mus sp. Species 0.000 description 13
- 230000004069 differentiation Effects 0.000 description 13
- 102000004169 proteins and genes Human genes 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 11
- 238000000692 Student's t-test Methods 0.000 description 11
- 230000001172 regenerating effect Effects 0.000 description 11
- 210000001519 tissue Anatomy 0.000 description 11
- 101100447432 Danio rerio gapdh-2 gene Proteins 0.000 description 10
- 101150112014 Gapdh gene Proteins 0.000 description 10
- 101710126211 POU domain, class 5, transcription factor 1 Proteins 0.000 description 10
- 238000003491 array Methods 0.000 description 10
- 238000003556 assay Methods 0.000 description 10
- 238000002955 isolation Methods 0.000 description 10
- 102000050389 Syntaxin Human genes 0.000 description 9
- 210000000411 amacrine cell Anatomy 0.000 description 9
- 101100247004 Rattus norvegicus Qsox1 gene Proteins 0.000 description 8
- 238000004113 cell culture Methods 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- NCYCYZXNIZJOKI-IOUUIBBYSA-N 11-cis-retinal Chemical compound O=C/C=C(\C)/C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-IOUUIBBYSA-N 0.000 description 7
- 102100028712 Cytosolic purine 5'-nucleotidase Human genes 0.000 description 7
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 7
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 7
- 108090001005 Interleukin-6 Proteins 0.000 description 7
- 108700011259 MicroRNAs Proteins 0.000 description 7
- 101100244964 Mus musculus Prkra gene Proteins 0.000 description 7
- 102000007354 PAX6 Transcription Factor Human genes 0.000 description 7
- 101150081664 PAX6 gene Proteins 0.000 description 7
- 101150116803 RAX gene Proteins 0.000 description 7
- 102000004330 Rhodopsin Human genes 0.000 description 7
- 108090000820 Rhodopsin Proteins 0.000 description 7
- 230000004913 activation Effects 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 210000002744 extracellular matrix Anatomy 0.000 description 7
- 230000008439 repair process Effects 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 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 6
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 6
- 102000053171 Glial Fibrillary Acidic Human genes 0.000 description 6
- 101710193519 Glial fibrillary acidic protein Proteins 0.000 description 6
- 102000000422 Matrix Metalloproteinase 3 Human genes 0.000 description 6
- 108010016160 Matrix Metalloproteinase 3 Proteins 0.000 description 6
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 6
- 230000006378 damage Effects 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 238000000684 flow cytometry Methods 0.000 description 6
- 210000005046 glial fibrillary acidic protein Anatomy 0.000 description 6
- 230000001939 inductive effect Effects 0.000 description 6
- 238000011068 loading method Methods 0.000 description 6
- 238000012423 maintenance Methods 0.000 description 6
- 230000004660 morphological change Effects 0.000 description 6
- 210000004940 nucleus Anatomy 0.000 description 6
- 230000037361 pathway Effects 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 210000003994 retinal ganglion cell Anatomy 0.000 description 6
- 102000003693 Hedgehog Proteins Human genes 0.000 description 5
- 108090000031 Hedgehog Proteins Proteins 0.000 description 5
- 101001076292 Homo sapiens Insulin-like growth factor II Proteins 0.000 description 5
- 102000026633 IL6 Human genes 0.000 description 5
- 102100025947 Insulin-like growth factor II Human genes 0.000 description 5
- 108700021430 Kruppel-Like Factor 4 Proteins 0.000 description 5
- 229940098773 bovine serum albumin Drugs 0.000 description 5
- 239000002299 complementary DNA Substances 0.000 description 5
- 239000000306 component Substances 0.000 description 5
- 230000000875 corresponding effect Effects 0.000 description 5
- 239000002158 endotoxin Substances 0.000 description 5
- 238000009396 hybridization Methods 0.000 description 5
- 102000006495 integrins Human genes 0.000 description 5
- 108010044426 integrins Proteins 0.000 description 5
- 101150111214 lin-28 gene Proteins 0.000 description 5
- 230000002062 proliferating effect Effects 0.000 description 5
- 238000011084 recovery Methods 0.000 description 5
- 238000005199 ultracentrifugation Methods 0.000 description 5
- 238000010200 validation analysis Methods 0.000 description 5
- 108010067219 Aggrecans Proteins 0.000 description 4
- 208000003098 Ganglion Cysts Diseases 0.000 description 4
- 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 4
- 101001094700 Homo sapiens POU domain, class 5, transcription factor 1 Proteins 0.000 description 4
- 101100137157 Mus musculus Pou5f1 gene Proteins 0.000 description 4
- -1 Nanog Proteins 0.000 description 4
- 239000013614 RNA sample Substances 0.000 description 4
- 102000039471 Small Nuclear RNA Human genes 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 208000005400 Synovial Cyst Diseases 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 238000012512 characterization method Methods 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000002716 delivery method Methods 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000002518 glial effect Effects 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 102000052983 human POU5F1 Human genes 0.000 description 4
- 238000003364 immunohistochemistry Methods 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 238000010172 mouse model Methods 0.000 description 4
- 238000010606 normalization Methods 0.000 description 4
- 239000008188 pellet Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000001737 promoting effect Effects 0.000 description 4
- 230000028396 retina morphogenesis in camera-type eye Effects 0.000 description 4
- 230000004243 retinal function Effects 0.000 description 4
- 210000000880 retinal rod photoreceptor cell Anatomy 0.000 description 4
- 102100036601 Aggrecan core protein Human genes 0.000 description 3
- 102100022544 Bone morphogenetic protein 7 Human genes 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- 102100035290 Fibroblast growth factor 13 Human genes 0.000 description 3
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 3
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 3
- 101000899361 Homo sapiens Bone morphogenetic protein 7 Proteins 0.000 description 3
- 101001078886 Homo sapiens Retinaldehyde-binding protein 1 Proteins 0.000 description 3
- 101100257363 Mus musculus Sox2 gene Proteins 0.000 description 3
- 102100028001 Retinaldehyde-binding protein 1 Human genes 0.000 description 3
- 108020004688 Small Nuclear RNA Proteins 0.000 description 3
- 102000040945 Transcription factor Human genes 0.000 description 3
- 108091023040 Transcription factor Proteins 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 230000001464 adherent effect Effects 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 210000003050 axon Anatomy 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000008758 canonical signaling Effects 0.000 description 3
- 230000033026 cell fate determination Effects 0.000 description 3
- 239000002771 cell marker Substances 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 238000000942 confocal micrograph Methods 0.000 description 3
- 208000021921 corneal disease Diseases 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 238000010195 expression analysis Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 3
- 239000010931 gold Substances 0.000 description 3
- 229910052737 gold Inorganic materials 0.000 description 3
- 210000002287 horizontal cell Anatomy 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 238000010208 microarray analysis Methods 0.000 description 3
- 238000000386 microscopy Methods 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000004224 protection Effects 0.000 description 3
- 210000001116 retinal neuron Anatomy 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 230000007838 tissue remodeling Effects 0.000 description 3
- 230000003827 upregulation Effects 0.000 description 3
- 102100029470 Apolipoprotein E Human genes 0.000 description 2
- 101710095339 Apolipoprotein E Proteins 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 102100021851 Calbindin Human genes 0.000 description 2
- 108010028310 Calbindin 1 Proteins 0.000 description 2
- 208000002177 Cataract Diseases 0.000 description 2
- 102000005598 Chondroitin Sulfate Proteoglycans Human genes 0.000 description 2
- 108010059480 Chondroitin Sulfate Proteoglycans Proteins 0.000 description 2
- 102000006312 Cyclin D2 Human genes 0.000 description 2
- 108010058544 Cyclin D2 Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 230000004544 DNA amplification Effects 0.000 description 2
- 102000034615 Glial cell line-derived neurotrophic factor Human genes 0.000 description 2
- 108091010837 Glial cell line-derived neurotrophic factor Proteins 0.000 description 2
- 101000738354 Homo sapiens CD9 antigen Proteins 0.000 description 2
- 101000746373 Homo sapiens Granulocyte-macrophage colony-stimulating factor Proteins 0.000 description 2
- 101000819074 Homo sapiens Transcription factor GATA-4 Proteins 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 238000002123 RNA extraction Methods 0.000 description 2
- 102100021380 Transcription factor GATA-4 Human genes 0.000 description 2
- 229920004890 Triton X-100 Polymers 0.000 description 2
- 239000013504 Triton X-100 Substances 0.000 description 2
- 102000013127 Vimentin Human genes 0.000 description 2
- 108010065472 Vimentin Proteins 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 239000012472 biological sample Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000008777 canonical pathway Effects 0.000 description 2
- 239000006143 cell culture medium Substances 0.000 description 2
- 230000022131 cell cycle Effects 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 230000006727 cell loss Effects 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000003636 conditioned culture medium Substances 0.000 description 2
- 108700041286 delta Proteins 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- FOCAHLGSDWHSAH-UHFFFAOYSA-N difluoromethanethione Chemical compound FC(F)=S FOCAHLGSDWHSAH-UHFFFAOYSA-N 0.000 description 2
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 2
- 230000003828 downregulation Effects 0.000 description 2
- 238000001493 electron microscopy Methods 0.000 description 2
- SEACYXSIPDVVMV-UHFFFAOYSA-L eosin Y Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C([O-])=C(Br)C=C21 SEACYXSIPDVVMV-UHFFFAOYSA-L 0.000 description 2
- 208000030533 eye disease Diseases 0.000 description 2
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 230000002055 immunohistochemical effect Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 210000004263 induced pluripotent stem cell Anatomy 0.000 description 2
- 239000000411 inducer Substances 0.000 description 2
- 210000004969 inflammatory cell Anatomy 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000004941 influx Effects 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000007775 late Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000012533 medium component Substances 0.000 description 2
- 230000031864 metaphase Effects 0.000 description 2
- 108091092012 miR-199b stem-loop Proteins 0.000 description 2
- 238000003253 miRNA assay Methods 0.000 description 2
- 230000000877 morphologic effect Effects 0.000 description 2
- 210000005157 neural retina Anatomy 0.000 description 2
- 108091027963 non-coding RNA Proteins 0.000 description 2
- 102000042567 non-coding RNA Human genes 0.000 description 2
- 210000001328 optic nerve Anatomy 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 238000003068 pathway analysis Methods 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 210000000608 photoreceptor cell Anatomy 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000002629 repopulating effect Effects 0.000 description 2
- 231100000241 scar Toxicity 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 230000023895 stem cell maintenance Effects 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 230000005740 tumor formation Effects 0.000 description 2
- 210000005048 vimentin Anatomy 0.000 description 2
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- HJCMDXDYPOUFDY-WHFBIAKZSA-N Ala-Gln Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O HJCMDXDYPOUFDY-WHFBIAKZSA-N 0.000 description 1
- 239000012103 Alexa Fluor 488 Substances 0.000 description 1
- 239000012109 Alexa Fluor 568 Substances 0.000 description 1
- 239000012110 Alexa Fluor 594 Substances 0.000 description 1
- 240000000662 Anethum graveolens Species 0.000 description 1
- 208000029910 Anterior chamber disease Diseases 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 101150073415 Aqp4 gene Proteins 0.000 description 1
- 102000012002 Aquaporin 4 Human genes 0.000 description 1
- 108010036280 Aquaporin 4 Proteins 0.000 description 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
- 108091032955 Bacterial small RNA Proteins 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 238000012756 BrdU staining Methods 0.000 description 1
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 1
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 1
- 102100032367 C-C motif chemokine 5 Human genes 0.000 description 1
- 102100032366 C-C motif chemokine 7 Human genes 0.000 description 1
- 101710155834 C-C motif chemokine 7 Proteins 0.000 description 1
- 101710098275 C-X-C motif chemokine 10 Proteins 0.000 description 1
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 1
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- 108010055166 Chemokine CCL5 Proteins 0.000 description 1
- 241000251556 Chordata Species 0.000 description 1
- 102000003780 Clusterin Human genes 0.000 description 1
- 108090000197 Clusterin Proteins 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 108010003730 Cone Opsins Proteins 0.000 description 1
- 206010010984 Corneal abrasion Diseases 0.000 description 1
- 208000028006 Corneal injury Diseases 0.000 description 1
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- 102000016911 Deoxyribonucleases Human genes 0.000 description 1
- 108010053770 Deoxyribonucleases Proteins 0.000 description 1
- 102100037985 Dickkopf-related protein 3 Human genes 0.000 description 1
- 101710099550 Dickkopf-related protein 3 Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 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 1
- 102100023688 Eotaxin Human genes 0.000 description 1
- 101710139422 Eotaxin Proteins 0.000 description 1
- 108700039887 Essential Genes Proteins 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 101150111020 GLUL gene Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 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
- 102000034575 Glutamate transporters Human genes 0.000 description 1
- 108091006151 Glutamate transporters Proteins 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 229920002971 Heparan sulfate Polymers 0.000 description 1
- 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 1
- 241000282412 Homo Species 0.000 description 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
- 101000934372 Homo sapiens Macrosialin Proteins 0.000 description 1
- 101000610551 Homo sapiens Prominin-1 Proteins 0.000 description 1
- 108091068992 Homo sapiens miR-143 stem-loop Proteins 0.000 description 1
- 108091067580 Homo sapiens miR-214 stem-loop Proteins 0.000 description 1
- 238000009015 Human TaqMan MicroRNA Assay kit Methods 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 102000003777 Interleukin-1 beta Human genes 0.000 description 1
- 108090000193 Interleukin-1 beta Proteins 0.000 description 1
- 102000003814 Interleukin-10 Human genes 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 102000014158 Interleukin-12 Subunit p40 Human genes 0.000 description 1
- 108010011429 Interleukin-12 Subunit p40 Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 108010065637 Interleukin-23 Proteins 0.000 description 1
- 102000013264 Interleukin-23 Human genes 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 239000012480 LAL reagent Substances 0.000 description 1
- 108090000581 Leukemia inhibitory factor Proteins 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- 102100025136 Macrosialin Human genes 0.000 description 1
- 206010064912 Malignant transformation Diseases 0.000 description 1
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 1
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 108091026807 MiR-214 Proteins 0.000 description 1
- 108091030146 MiRBase Proteins 0.000 description 1
- 108091027766 Mir-143 Proteins 0.000 description 1
- 108091027559 Mir-96 microRNA Proteins 0.000 description 1
- 101710151805 Mitochondrial intermediate peptidase 1 Proteins 0.000 description 1
- 101100165560 Mus musculus Bmp7 gene Proteins 0.000 description 1
- 101100501720 Mus musculus Erg gene Proteins 0.000 description 1
- 101100506445 Mus musculus Helt gene Proteins 0.000 description 1
- 101100404103 Mus musculus Nanog gene Proteins 0.000 description 1
- 108091069314 Mus musculus miR-294 stem-loop Proteins 0.000 description 1
- 108091069315 Mus musculus miR-295 stem-loop Proteins 0.000 description 1
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- 210000005156 Müller Glia Anatomy 0.000 description 1
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 1
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 1
- HOKKHZGPKSLGJE-UHFFFAOYSA-N N-methyl-D-aspartic acid Natural products CNC(C(O)=O)CC(O)=O HOKKHZGPKSLGJE-UHFFFAOYSA-N 0.000 description 1
- 206010056677 Nerve degeneration Diseases 0.000 description 1
- 102000014413 Neuregulin Human genes 0.000 description 1
- 108050003475 Neuregulin Proteins 0.000 description 1
- 102100032063 Neurogenic differentiation factor 1 Human genes 0.000 description 1
- 108050000588 Neurogenic differentiation factor 1 Proteins 0.000 description 1
- 108700037638 Neurogenic locus notch homolog protein 1 Proteins 0.000 description 1
- 230000005913 Notch signaling pathway Effects 0.000 description 1
- 108010029751 Notch2 Receptor Proteins 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 108060005874 Parvalbumin Proteins 0.000 description 1
- 102000001675 Parvalbumin Human genes 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 102100026296 Protein S100-A16 Human genes 0.000 description 1
- 101710110941 Protein S100-A16 Proteins 0.000 description 1
- 238000013381 RNA quantification Methods 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 208000032430 Retinal dystrophy Diseases 0.000 description 1
- 206010057430 Retinal injury Diseases 0.000 description 1
- 108091006629 SLC13A2 Proteins 0.000 description 1
- 108091006283 SLC17A7 Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 102000013265 Syntaxin 1 Human genes 0.000 description 1
- 108010090618 Syntaxin 1 Proteins 0.000 description 1
- 102000007000 Tenascin Human genes 0.000 description 1
- 108010008125 Tenascin Proteins 0.000 description 1
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 108091026822 U6 spliceosomal RNA Proteins 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 102000046052 Vesicular Glutamate Transport Protein 1 Human genes 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
- 241001148470 aerobic bacillus Species 0.000 description 1
- 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 1
- 210000001284 amacrine neuron Anatomy 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000019552 anatomical structure morphogenesis Effects 0.000 description 1
- 230000001405 anti-neuronal effect Effects 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 230000003376 axonal effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 230000006369 cell cycle progression Effects 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000009087 cell motility Effects 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 230000017455 cell-cell adhesion Effects 0.000 description 1
- 230000023549 cell-cell signaling Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 238000004624 confocal microscopy Methods 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- ALEXXDVDDISNDU-JZYPGELDSA-N cortisol 21-acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O ALEXXDVDDISNDU-JZYPGELDSA-N 0.000 description 1
- 210000004395 cytoplasmic granule Anatomy 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 238000001085 differential centrifugation Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000003503 early effect Effects 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 230000037149 energy metabolism Effects 0.000 description 1
- 239000004060 excitotoxin Substances 0.000 description 1
- 238000013265 extended release Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000011536 extraction buffer Substances 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000003633 gene expression assay Methods 0.000 description 1
- 238000011223 gene expression profiling Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 230000002962 histologic effect Effects 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000003365 immunocytochemistry Methods 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 208000017532 inherited retinal dystrophy Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000036212 malign transformation Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- RHCSKNNOAZULRK-UHFFFAOYSA-N mescaline Chemical compound COC1=CC(CCN)=CC(OC)=C1OC RHCSKNNOAZULRK-UHFFFAOYSA-N 0.000 description 1
- 108091028606 miR-1 stem-loop Proteins 0.000 description 1
- 108091079012 miR-133a Proteins 0.000 description 1
- 108091024038 miR-133a stem-loop Proteins 0.000 description 1
- 108091032320 miR-146 stem-loop Proteins 0.000 description 1
- 108091024530 miR-146a stem-loop Proteins 0.000 description 1
- 108091023796 miR-182 stem-loop Proteins 0.000 description 1
- 108091029500 miR-183 stem-loop Proteins 0.000 description 1
- 108091068695 miR-291b stem-loop Proteins 0.000 description 1
- 108091072810 miR-294 stem-loop Proteins 0.000 description 1
- 108091023818 miR-7 stem-loop Proteins 0.000 description 1
- 108091086713 miR-96 stem-loop Proteins 0.000 description 1
- 108091070961 miR-96-3 stem-loop Proteins 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 238000011206 morphological examination Methods 0.000 description 1
- 210000005088 multinucleated cell Anatomy 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 230000001114 myogenic effect Effects 0.000 description 1
- 230000032405 negative regulation of neuron apoptotic process Effects 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 210000003757 neuroblast Anatomy 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 230000014511 neuron projection development Effects 0.000 description 1
- 231100001221 nontumorigenic Toxicity 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 230000008816 organ damage Effects 0.000 description 1
- 230000005305 organ development Effects 0.000 description 1
- 230000008212 organismal development Effects 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000009979 protective mechanism Effects 0.000 description 1
- 238000000751 protein extraction Methods 0.000 description 1
- 238000000575 proteomic method Methods 0.000 description 1
- 230000002488 pyknotic effect Effects 0.000 description 1
- 238000003762 quantitative reverse transcription PCR Methods 0.000 description 1
- 239000003642 reactive oxygen metabolite Substances 0.000 description 1
- 230000008458 response to injury Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000004281 retinal morphology Effects 0.000 description 1
- 229930002330 retinoic acid Natural products 0.000 description 1
- 230000003289 retinoprotective effect Effects 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 230000036573 scar formation Effects 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 210000004683 skeletal myoblast Anatomy 0.000 description 1
- 108091029842 small nuclear ribonucleic acid Proteins 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 210000004500 stellate cell Anatomy 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 241001148471 unidentified anaerobic bacterium Species 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 102000009310 vitamin D receptors Human genes 0.000 description 1
- 108050000156 vitamin D receptors Proteins 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000001262 western blot Methods 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
- C12N5/0603—Embryonic cells ; Embryoid bodies
- C12N5/0606—Pluripotent embryonic cells, e.g. embryonic stem cells [ES]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/48—Reproductive organs
- A61K35/54—Ovaries; Ova; Ovules; Embryos; Foetal cells; Germ cells
- A61K35/545—Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/12—Ophthalmic agents for cataracts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- C12N5/0621—Eye cells, e.g. cornea, iris pigmented 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
- C12N5/0618—Cells of the nervous system
- C12N5/0622—Glial cells, e.g. astrocytes, oligodendrocytes; Schwann 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
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/02—Coculture with; Conditioned medium produced by embryonic cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/45—Artificially induced pluripotent stem cells
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Zoology (AREA)
- Developmental Biology & Embryology (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Reproductive Health (AREA)
- Ophthalmology & Optometry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Gynecology & Obstetrics (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261624701P | 2012-04-16 | 2012-04-16 | |
| US61/624,701 | 2012-04-16 | ||
| PCT/US2013/030733 WO2013158258A1 (en) | 2012-04-16 | 2013-03-13 | Ocular therapeutics using embryonic system cell microvesicles |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2870466A1 true CA2870466A1 (en) | 2013-10-24 |
Family
ID=49383920
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2870466A Abandoned CA2870466A1 (en) | 2012-04-16 | 2013-03-13 | Ocular therapeutics using embryonic stem cell microvesicles |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US20150079047A1 (enExample) |
| EP (1) | EP2838995A4 (enExample) |
| JP (1) | JP2015514760A (enExample) |
| KR (1) | KR20150009541A (enExample) |
| AU (1) | AU2013249786A1 (enExample) |
| CA (1) | CA2870466A1 (enExample) |
| IL (1) | IL235126A0 (enExample) |
| WO (1) | WO2013158258A1 (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101334404B1 (ko) * | 2011-04-28 | 2013-12-12 | 포항공과대학교 산학협력단 | 배아줄기세포 유래의 인공 마이크로베시클을 이용한 역분화 유도만능줄기세포의 제조방법 |
| EP3512948A4 (en) * | 2016-09-09 | 2020-05-13 | Cornell University | ADMINISTRATION OF NUCLEIC ACIDS, PROTEINS AND SMALL MOLECULES IN GLASS-LIKE VESICULAR BODIES |
| US11653636B2 (en) * | 2019-11-15 | 2023-05-23 | University Of Ulsan Foundation For Industry Cooperation | Method of making a rat model of retinal degeneration and rat model made thereby |
| JP7007770B1 (ja) * | 2021-06-21 | 2022-02-10 | パナジー株式会社 | 眼症状改善剤および眼症状の改善方法 |
| KR20230129828A (ko) | 2022-03-02 | 2023-09-11 | 포항공과대학교 산학협력단 | 안구 후방 질환 또는 손상의 예방 또는 치료용 조성물 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5824685A (en) * | 1995-02-01 | 1998-10-20 | The Johns Hopkins University School Of Medicine | Method of preventing proliferation of retinal pigment epithelium by retinoic acid receptor agonists |
| CA2493122C (en) * | 2002-07-25 | 2012-11-27 | The Scripps Research Institute | Hematopoietic stem cells and methods of treatment of neovascular eye diseases therewith |
| AU2003280824A1 (en) * | 2002-11-15 | 2004-06-15 | Fumihiko Ishikawa | Method of organ regeneration |
| US20080317721A1 (en) * | 2005-02-24 | 2008-12-25 | The Scripps Research Institute | Method for the Treatment of Retinopathy of Prematurity and Related Retinopathic Diseases |
| KR20080031474A (ko) * | 2005-07-27 | 2008-04-08 | 유니버시티 오브 플로리다 리서치 파운데이션, 아이엔씨. | 안구 질환의 치료를 위한 열충격의 사용 |
| JP5649786B2 (ja) * | 2006-03-07 | 2015-01-07 | ギータ シュロフ | ヒト胚性幹細胞およびそれらの誘導体を含む組成物、使用方法、ならびに調製方法 |
| CN101854941B (zh) * | 2007-10-29 | 2013-03-27 | 弗雷森纽斯医疗护理德国有限责任公司 | 衍生自干细胞的微泡(MVs)用于制备用于受损或损伤组织或器官的内皮/上皮再生的药物的用途、以及相关体外和体内方法 |
| AU2009203638C1 (en) * | 2008-01-04 | 2013-07-25 | Lydac Neuroscience Limited | Microvesicles |
| EP2486126B1 (en) * | 2009-10-06 | 2017-12-06 | SNU R & DB Foundation | Method for differentiation into retinal cells from stem cells |
| WO2012020308A2 (en) * | 2010-08-13 | 2012-02-16 | The University Court Of The University Of Glasgow | Cellular and molecular therapies |
| JP5872041B2 (ja) * | 2011-08-16 | 2016-03-01 | サムスン ライフ パブリック ウェルフェア ファンデーション | 幹細胞由来微小胞を含む神経生成促進用組成物 |
| EP2866816A4 (en) * | 2012-05-31 | 2016-03-16 | Caladrius Biosciences Inc | VERY SMALL HUMAN EMBRYONIC STEM CELLS FOR THE TREATMENT OF EYE DISEASES |
-
2013
- 2013-03-13 EP EP13778372.6A patent/EP2838995A4/en not_active Withdrawn
- 2013-03-13 CA CA2870466A patent/CA2870466A1/en not_active Abandoned
- 2013-03-13 WO PCT/US2013/030733 patent/WO2013158258A1/en not_active Ceased
- 2013-03-13 JP JP2015506995A patent/JP2015514760A/ja active Pending
- 2013-03-13 AU AU2013249786A patent/AU2013249786A1/en not_active Abandoned
- 2013-03-13 KR KR1020147031795A patent/KR20150009541A/ko not_active Withdrawn
- 2013-03-13 US US14/394,688 patent/US20150079047A1/en not_active Abandoned
-
2014
- 2014-10-19 IL IL235126A patent/IL235126A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO2013158258A1 (en) | 2013-10-24 |
| EP2838995A1 (en) | 2015-02-25 |
| EP2838995A4 (en) | 2016-01-06 |
| US20150079047A1 (en) | 2015-03-19 |
| KR20150009541A (ko) | 2015-01-26 |
| AU2013249786A1 (en) | 2014-11-06 |
| JP2015514760A (ja) | 2015-05-21 |
| IL235126A0 (en) | 2014-12-31 |
| WO2013158258A8 (en) | 2014-09-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Katsman et al. | Embryonic stem cell-derived microvesicles induce gene expression changes in Müller cells of the retina | |
| Dubbelaar et al. | The kaleidoscope of microglial phenotypes | |
| Roybon et al. | Human stem cell-derived spinal cord astrocytes with defined mature or reactive phenotypes | |
| Sun et al. | Mutations in the transcriptional regulator MeCP2 severely impact key cellular and molecular signatures of human astrocytes during maturation | |
| CN104321062B (zh) | 干细胞微粒 | |
| US20150079047A1 (en) | Ocular therapeutics using embryonic stem cell microvesicles | |
| TR201903889T4 (tr) | Korneal endotelyal hücreler üreten yönlendirilmiş diferansiyasyona yönelik yöntem. | |
| CN104718283A (zh) | 从头生成多能细胞 | |
| JP2015510401A (ja) | ヒト疾患のインビトロモデル化および細胞に基づく治療のための間葉系幹細胞ならびにそのバンク | |
| Lozano-Ureña et al. | IGF2 interacts with the imprinted gene Cdkn1c to promote terminal differentiation of neural stem cells | |
| De Filippis et al. | Neural stem cells and human induced pluripotent stem cells to model rare CNS diseases | |
| Lattanzi et al. | Neurotrophic features of human adipose tissue‐derived stromal cells: in vitro and in vivo studies | |
| Kang et al. | RETRACTED ARTICLE: Stem-like cells of various origins showed therapeutic effect to improve the recovery of spinal cord injury | |
| Hsi et al. | Extracellular vesicles as biomarkers for traumatic brain injury using a 3D in vitro human brain tissue model | |
| JP2025111573A (ja) | 高増殖性細胞の製造方法、高増殖性細胞およびその用途 | |
| US20240254440A1 (en) | Methods to generate glial restricted neural progenitor cells and uses thereof | |
| CN119584975A (zh) | 治疗脑损伤的方法 | |
| KR20180117070A (ko) | 신규 줄기세포 치료제 | |
| Ali et al. | Directed differentiation of umbilical cord blood stem cells into cortical GABAergic neurons | |
| Xu et al. | Reversing abnormal neural development by inhibiting OLIG2 in down syndrome human iPSC brain organoids and neuronal mouse chimeras | |
| US20250382570A1 (en) | Generation and application of functional human astrocytes from pluripotent stem cells | |
| Rümmele | Exploring the regulation of human neural stem cells quiescence using a CRISPR/Cas9 approach | |
| Lovejoy | iPSC derived cerebral organoids as a model of tauopathy | |
| Sun | Exploring the Cellular and Molecular Features of Human Astrocytes with Rett Syndrome-Causing MEPC2 Mutations | |
| Hou et al. | and Hung-Chih Kuo |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20190313 |