ES2530370T5 - Células del epitelio pigmentario de la retina derivadas de células madre - Google Patents
Células del epitelio pigmentario de la retina derivadas de células madre Download PDFInfo
- Publication number
- ES2530370T5 ES2530370T5 ES12181140.0T ES12181140T ES2530370T5 ES 2530370 T5 ES2530370 T5 ES 2530370T5 ES 12181140 T ES12181140 T ES 12181140T ES 2530370 T5 ES2530370 T5 ES 2530370T5
- Authority
- ES
- Spain
- Prior art keywords
- cells
- rpe
- differentiation
- hesc
- 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.)
- Active
Links
- 210000000130 stem cell Anatomy 0.000 title description 27
- 210000000844 retinal pigment epithelial cell Anatomy 0.000 title description 5
- 210000004027 cell Anatomy 0.000 claims description 459
- 210000003583 retinal pigment epithelium Anatomy 0.000 claims description 269
- 230000004069 differentiation Effects 0.000 claims description 155
- 241000282414 Homo sapiens Species 0.000 claims description 58
- 108010023082 activin A Proteins 0.000 claims description 57
- 238000000034 method Methods 0.000 claims description 55
- 238000002054 transplantation Methods 0.000 claims description 34
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 19
- 210000001671 embryonic stem cell Anatomy 0.000 claims description 17
- 238000012258 culturing Methods 0.000 claims description 12
- 235000005152 nicotinamide Nutrition 0.000 claims description 10
- 239000011570 nicotinamide Substances 0.000 claims description 10
- 229960003966 nicotinamide Drugs 0.000 claims description 10
- 102000009618 Transforming Growth Factors Human genes 0.000 claims description 7
- 108010009583 Transforming Growth Factors Proteins 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 210000001778 pluripotent stem cell Anatomy 0.000 claims description 3
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims 1
- 230000014509 gene expression Effects 0.000 description 78
- 210000001508 eye Anatomy 0.000 description 60
- 239000002609 medium Substances 0.000 description 50
- 210000001525 retina Anatomy 0.000 description 41
- 101000729271 Homo sapiens Retinoid isomerohydrolase Proteins 0.000 description 31
- 102100031176 Retinoid isomerohydrolase Human genes 0.000 description 31
- 230000001965 increasing effect Effects 0.000 description 30
- 230000000694 effects Effects 0.000 description 29
- 241000700159 Rattus Species 0.000 description 27
- 108091008695 photoreceptors Proteins 0.000 description 27
- 239000003102 growth factor Substances 0.000 description 25
- 239000003550 marker Substances 0.000 description 25
- 238000004458 analytical method Methods 0.000 description 22
- 108050002823 Bestrophin Proteins 0.000 description 21
- 102000012304 Bestrophin Human genes 0.000 description 21
- 238000004113 cell culture Methods 0.000 description 21
- 230000006870 function Effects 0.000 description 19
- 238000001727 in vivo Methods 0.000 description 18
- 239000010410 layer Substances 0.000 description 18
- 108090000623 proteins and genes Proteins 0.000 description 18
- 230000002269 spontaneous effect Effects 0.000 description 18
- 238000011161 development Methods 0.000 description 17
- 230000018109 developmental process Effects 0.000 description 17
- 230000001939 inductive effect Effects 0.000 description 16
- 230000019612 pigmentation Effects 0.000 description 15
- 238000003753 real-time PCR Methods 0.000 description 15
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 14
- 230000001537 neural effect Effects 0.000 description 14
- 230000008569 process Effects 0.000 description 13
- 108020004414 DNA Proteins 0.000 description 12
- 238000001000 micrograph Methods 0.000 description 11
- 230000002207 retinal effect Effects 0.000 description 11
- 108010059616 Activins Proteins 0.000 description 10
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 10
- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 10
- 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 10
- 102100026818 Inhibin beta E chain Human genes 0.000 description 10
- 239000000488 activin Substances 0.000 description 10
- 229940112869 bone morphogenetic protein Drugs 0.000 description 10
- 238000010494 dissociation reaction Methods 0.000 description 10
- 230000005593 dissociations Effects 0.000 description 10
- 210000002950 fibroblast Anatomy 0.000 description 10
- 208000002780 macular degeneration Diseases 0.000 description 10
- 230000000877 morphologic effect Effects 0.000 description 10
- 230000004044 response Effects 0.000 description 10
- 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 9
- 241001465754 Metazoa Species 0.000 description 9
- 102000004330 Rhodopsin Human genes 0.000 description 9
- 108090000820 Rhodopsin Proteins 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 238000012744 immunostaining Methods 0.000 description 9
- 101150087532 mitF gene Proteins 0.000 description 9
- 241000283707 Capra Species 0.000 description 8
- 238000002571 electroretinography Methods 0.000 description 8
- 239000001963 growth medium Substances 0.000 description 8
- 239000002953 phosphate buffered saline Substances 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 7
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 7
- 108090000526 Papain Proteins 0.000 description 7
- 239000004365 Protease Substances 0.000 description 7
- 201000007737 Retinal degeneration Diseases 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 210000002304 esc Anatomy 0.000 description 7
- 210000002744 extracellular matrix Anatomy 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 229940055729 papain Drugs 0.000 description 7
- 235000019834 papain Nutrition 0.000 description 7
- 239000002243 precursor Substances 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 230000004258 retinal degeneration Effects 0.000 description 7
- 210000002966 serum Anatomy 0.000 description 7
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 6
- 101001078886 Homo sapiens Retinaldehyde-binding protein 1 Proteins 0.000 description 6
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 6
- 101150092239 OTX2 gene Proteins 0.000 description 6
- 102000007354 PAX6 Transcription Factor Human genes 0.000 description 6
- 101150081664 PAX6 gene Proteins 0.000 description 6
- 206010057249 Phagocytosis Diseases 0.000 description 6
- 102100028001 Retinaldehyde-binding protein 1 Human genes 0.000 description 6
- 208000007014 Retinitis pigmentosa Diseases 0.000 description 6
- 206010064930 age-related macular degeneration Diseases 0.000 description 6
- 239000011324 bead Substances 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 6
- 238000003384 imaging method Methods 0.000 description 6
- 230000006698 induction Effects 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 230000008782 phagocytosis Effects 0.000 description 6
- 239000000049 pigment Substances 0.000 description 6
- 238000007747 plating Methods 0.000 description 6
- 230000035755 proliferation Effects 0.000 description 6
- 230000002035 prolonged effect Effects 0.000 description 6
- 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 6
- 230000004083 survival effect Effects 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 201000004569 Blindness Diseases 0.000 description 5
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 5
- 108010085895 Laminin Proteins 0.000 description 5
- 101150082854 Mertk gene Proteins 0.000 description 5
- 241000283973 Oryctolagus cuniculus Species 0.000 description 5
- 239000006285 cell suspension Substances 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 5
- 230000001605 fetal effect Effects 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 201000010260 leiomyoma Diseases 0.000 description 5
- 230000000670 limiting effect Effects 0.000 description 5
- 238000004321 preservation Methods 0.000 description 5
- 230000001737 promoting effect Effects 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 230000001228 trophic effect Effects 0.000 description 5
- 239000013598 vector Substances 0.000 description 5
- 102000007469 Actins Human genes 0.000 description 4
- 108010085238 Actins Proteins 0.000 description 4
- 108010005853 Anti-Mullerian Hormone Proteins 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 206010025412 Macular dystrophy congenital Diseases 0.000 description 4
- 102100030173 Muellerian-inhibiting factor Human genes 0.000 description 4
- 102000008730 Nestin Human genes 0.000 description 4
- 108010088225 Nestin Proteins 0.000 description 4
- 238000010240 RT-PCR analysis Methods 0.000 description 4
- 206010043276 Teratoma Diseases 0.000 description 4
- 238000004115 adherent culture Methods 0.000 description 4
- 239000000868 anti-mullerian hormone Substances 0.000 description 4
- 229960000074 biopharmaceutical Drugs 0.000 description 4
- 230000000875 corresponding effect Effects 0.000 description 4
- 210000004748 cultured cell Anatomy 0.000 description 4
- 230000007850 degeneration Effects 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000004064 dysfunction Effects 0.000 description 4
- 238000001493 electron microscopy Methods 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 230000004438 eyesight Effects 0.000 description 4
- 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 4
- 239000011521 glass Substances 0.000 description 4
- 239000004816 latex Substances 0.000 description 4
- 229920000126 latex Polymers 0.000 description 4
- 238000012423 maintenance Methods 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 210000005055 nestin Anatomy 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000000750 progressive effect Effects 0.000 description 4
- 238000011002 quantification Methods 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 201000007790 vitelliform macular dystrophy Diseases 0.000 description 4
- 101100295848 Drosophila melanogaster Optix gene Proteins 0.000 description 3
- 241000283074 Equus asinus Species 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 206010025421 Macule Diseases 0.000 description 3
- 102100035423 POU domain, class 5, transcription factor 1 Human genes 0.000 description 3
- 101710126211 POU domain, class 5, transcription factor 1 Proteins 0.000 description 3
- 229930182555 Penicillin Natural products 0.000 description 3
- 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 3
- 108700010572 Sine oculis homeobox homolog 3 Proteins 0.000 description 3
- 102000004142 Trypsin Human genes 0.000 description 3
- 108090000631 Trypsin Proteins 0.000 description 3
- 230000003321 amplification Effects 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 210000002469 basement membrane Anatomy 0.000 description 3
- 239000006143 cell culture medium Substances 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 210000003161 choroid Anatomy 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000009795 derivation Methods 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 210000002257 embryonic structure Anatomy 0.000 description 3
- 239000003797 essential amino acid Substances 0.000 description 3
- 235000020776 essential amino acid Nutrition 0.000 description 3
- 210000003754 fetus Anatomy 0.000 description 3
- 238000000684 flow cytometry Methods 0.000 description 3
- 210000004602 germ cell Anatomy 0.000 description 3
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 3
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 238000010166 immunofluorescence Methods 0.000 description 3
- 230000002055 immunohistochemical effect Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000000977 initiatory effect Effects 0.000 description 3
- 230000004807 localization Effects 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 210000002752 melanocyte Anatomy 0.000 description 3
- 210000004379 membrane Anatomy 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 210000000110 microvilli Anatomy 0.000 description 3
- 238000003199 nucleic acid amplification method Methods 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 150000007523 nucleic acids Chemical class 0.000 description 3
- 235000015097 nutrients Nutrition 0.000 description 3
- 230000003076 paracrine Effects 0.000 description 3
- 229940049954 penicillin Drugs 0.000 description 3
- 238000003752 polymerase chain reaction Methods 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 230000035935 pregnancy Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000008929 regeneration Effects 0.000 description 3
- 238000011069 regeneration method Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 230000004243 retinal function Effects 0.000 description 3
- 210000001082 somatic cell Anatomy 0.000 description 3
- 101150077014 sox10 gene Proteins 0.000 description 3
- 229960005322 streptomycin Drugs 0.000 description 3
- 238000004114 suspension culture Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000032258 transport Effects 0.000 description 3
- 239000012588 trypsin Substances 0.000 description 3
- 102100024504 Bone morphogenetic protein 3 Human genes 0.000 description 2
- 102100024505 Bone morphogenetic protein 4 Human genes 0.000 description 2
- 102100022526 Bone morphogenetic protein 5 Human genes 0.000 description 2
- 102100022525 Bone morphogenetic protein 6 Human genes 0.000 description 2
- 102100022544 Bone morphogenetic protein 7 Human genes 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 102000029816 Collagenase Human genes 0.000 description 2
- 108060005980 Collagenase Proteins 0.000 description 2
- 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 2
- 108010036949 Cyclosporine Proteins 0.000 description 2
- 108010067306 Fibronectins Proteins 0.000 description 2
- 102000016359 Fibronectins Human genes 0.000 description 2
- 101000762375 Homo sapiens Bone morphogenetic protein 3 Proteins 0.000 description 2
- 101000762379 Homo sapiens Bone morphogenetic protein 4 Proteins 0.000 description 2
- 101000899388 Homo sapiens Bone morphogenetic protein 5 Proteins 0.000 description 2
- 101000899390 Homo sapiens Bone morphogenetic protein 6 Proteins 0.000 description 2
- 101000899361 Homo sapiens Bone morphogenetic protein 7 Proteins 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 102100034343 Integrase Human genes 0.000 description 2
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- KPKZJLCSROULON-QKGLWVMZSA-N Phalloidin Chemical compound N1C(=O)[C@@H]([C@@H](O)C)NC(=O)[C@H](C)NC(=O)[C@H](C[C@@](C)(O)CO)NC(=O)[C@H](C2)NC(=O)[C@H](C)NC(=O)[C@@H]3C[C@H](O)CN3C(=O)[C@@H]1CSC1=C2C2=CC=CC=C2N1 KPKZJLCSROULON-QKGLWVMZSA-N 0.000 description 2
- 238000001190 Q-PCR Methods 0.000 description 2
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 2
- 101100437153 Rattus norvegicus Acvr2b gene Proteins 0.000 description 2
- 206010057430 Retinal injury Diseases 0.000 description 2
- 229920004890 Triton X-100 Polymers 0.000 description 2
- BGDKAVGWHJFAGW-UHFFFAOYSA-N Tropicamide Chemical compound C=1C=CC=CC=1C(CO)C(=O)N(CC)CC1=CC=NC=C1 BGDKAVGWHJFAGW-UHFFFAOYSA-N 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- -1 ZO-1 Proteins 0.000 description 2
- 108010023079 activin B Proteins 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 210000004381 amniotic fluid Anatomy 0.000 description 2
- 230000003190 augmentative effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 239000007978 cacodylate buffer Substances 0.000 description 2
- 230000011712 cell development Effects 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 210000004240 ciliary body Anatomy 0.000 description 2
- 230000004186 co-expression Effects 0.000 description 2
- 230000008045 co-localization Effects 0.000 description 2
- 229960002424 collagenase Drugs 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 210000004087 cornea Anatomy 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000002224 dissection Methods 0.000 description 2
- 230000007159 enucleation Effects 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 239000007850 fluorescent dye Substances 0.000 description 2
- 210000003953 foreskin Anatomy 0.000 description 2
- 238000012239 gene modification Methods 0.000 description 2
- 230000005017 genetic modification Effects 0.000 description 2
- 235000013617 genetically modified food Nutrition 0.000 description 2
- 210000004392 genitalia Anatomy 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 2
- 238000003125 immunofluorescent labeling Methods 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 210000004263 induced pluripotent stem cell Anatomy 0.000 description 2
- 239000000411 inducer Substances 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 208000018769 loss of vision Diseases 0.000 description 2
- 231100000864 loss of vision Toxicity 0.000 description 2
- 230000007257 malfunction Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 238000000386 microscopy Methods 0.000 description 2
- 238000009126 molecular therapy Methods 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 230000004031 neuronal differentiation Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 230000000242 pagocytic effect Effects 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 2
- 238000004064 recycling Methods 0.000 description 2
- 230000001172 regenerating effect Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 230000000392 somatic effect Effects 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 238000004627 transmission electron microscopy Methods 0.000 description 2
- 229960004791 tropicamide Drugs 0.000 description 2
- 210000003954 umbilical cord Anatomy 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- 230000004393 visual impairment Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 2
- 229960001600 xylazine Drugs 0.000 description 2
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- BUOYTFVLNZIELF-UHFFFAOYSA-N 2-phenyl-1h-indole-4,6-dicarboximidamide Chemical compound N1C2=CC(C(=N)N)=CC(C(N)=N)=C2C=C1C1=CC=CC=C1 BUOYTFVLNZIELF-UHFFFAOYSA-N 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- UPXRTVAIJMUAQR-UHFFFAOYSA-N 4-(9h-fluoren-9-ylmethoxycarbonylamino)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound C1C(C(O)=O)N(C(=O)OC(C)(C)C)CC1NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 UPXRTVAIJMUAQR-UHFFFAOYSA-N 0.000 description 1
- 102000018918 Activin Receptors Human genes 0.000 description 1
- 108010052946 Activin Receptors Proteins 0.000 description 1
- 102100021886 Activin receptor type-2A Human genes 0.000 description 1
- 101710191686 Activin receptor type-2A Proteins 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 102100024506 Bone morphogenetic protein 2 Human genes 0.000 description 1
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 1
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000033810 Choroidal dystrophy Diseases 0.000 description 1
- 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 description 1
- 102100031614 Ciliary neurotrophic factor Human genes 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- 101100296720 Dictyostelium discoideum Pde4 gene Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
- 101150001754 Gusb gene Proteins 0.000 description 1
- 101000762366 Homo sapiens Bone morphogenetic protein 2 Proteins 0.000 description 1
- 101001002170 Homo sapiens Glutamine amidotransferase-like class 1 domain-containing protein 3, mitochondrial Proteins 0.000 description 1
- 101000843556 Homo sapiens Transcription factor HES-1 Proteins 0.000 description 1
- 101001010792 Homo sapiens Transcriptional regulator ERG Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 201000003533 Leber congenital amaurosis Diseases 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 208000035719 Maculopathy Diseases 0.000 description 1
- 241000713869 Moloney murine leukemia virus Species 0.000 description 1
- 208000006550 Mydriasis Diseases 0.000 description 1
- BAWFJGJZGIEFAR-NNYOXOHSSA-N NAD zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-N 0.000 description 1
- 101150096752 NCAM1 gene Proteins 0.000 description 1
- 108010025020 Nerve Growth Factor Proteins 0.000 description 1
- 102000007072 Nerve Growth Factors Human genes 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 208000022873 Ocular disease Diseases 0.000 description 1
- 238000002944 PCR assay Methods 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 208000034247 Pattern dystrophy Diseases 0.000 description 1
- 108010009711 Phalloidine Proteins 0.000 description 1
- 101100082610 Plasmodium falciparum (isolate 3D7) PDEdelta gene Proteins 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 102100020949 Putative glutamine amidotransferase-like class 1 domain-containing protein 3B, mitochondrial Human genes 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- 101100287688 Rattus norvegicus Kcnh2 gene Proteins 0.000 description 1
- 229940127361 Receptor Tyrosine Kinase Inhibitors Drugs 0.000 description 1
- 108700005075 Regulator Genes Proteins 0.000 description 1
- 206010038848 Retinal detachment Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000027073 Stargardt disease Diseases 0.000 description 1
- 239000012163 TRI reagent Substances 0.000 description 1
- 108010006785 Taq Polymerase Proteins 0.000 description 1
- 206010043275 Teratogenicity Diseases 0.000 description 1
- QIOZLISABUUKJY-UHFFFAOYSA-N Thiobenzamide Chemical class NC(=S)C1=CC=CC=C1 QIOZLISABUUKJY-UHFFFAOYSA-N 0.000 description 1
- 241000695776 Thorichthys aureus Species 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- COQLPRJCUIATTQ-UHFFFAOYSA-N Uranyl acetate Chemical compound O.O.O=[U]=O.CC(O)=O.CC(O)=O COQLPRJCUIATTQ-UHFFFAOYSA-N 0.000 description 1
- 108091008605 VEGF receptors Proteins 0.000 description 1
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- 230000019552 anatomical structure morphogenesis Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 230000000712 assembly Effects 0.000 description 1
- 238000000429 assembly Methods 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 230000000721 bacterilogical effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000010256 biochemical assay Methods 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- HOQPTLCRWVZIQZ-UHFFFAOYSA-H bis[[2-(5-hydroxy-4,7-dioxo-1,3,2$l^{2}-dioxaplumbepan-5-yl)acetyl]oxy]lead Chemical compound [Pb+2].[Pb+2].[Pb+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HOQPTLCRWVZIQZ-UHFFFAOYSA-H 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000004271 bone marrow stromal cell Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 102000002717 c-Mer Tyrosine Kinase Human genes 0.000 description 1
- 108010018804 c-Mer Tyrosine Kinase Proteins 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000002771 cell marker Substances 0.000 description 1
- 239000013553 cell monolayer Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 208000003571 choroideremia Diseases 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 238000004624 confocal microscopy Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 239000000994 contrast dye Substances 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000004300 dark adaptation Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000004414 early eye development Effects 0.000 description 1
- 210000003981 ectoderm Anatomy 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 210000001900 endoderm Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000007824 enzymatic assay Methods 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 210000000646 extraembryonic cell Anatomy 0.000 description 1
- 230000004373 eye development Effects 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 210000004700 fetal blood Anatomy 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000005714 functional activity Effects 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
- 210000001654 germ layer Anatomy 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 210000002149 gonad Anatomy 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000010185 immunofluorescence analysis Methods 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 229940039412 ketalar Drugs 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 229960004184 ketamine hydrochloride Drugs 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 210000003716 mesoderm Anatomy 0.000 description 1
- 230000001617 migratory effect Effects 0.000 description 1
- 238000004264 monolayer culture Methods 0.000 description 1
- 239000012120 mounting media Substances 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 229950006238 nadide Drugs 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 210000000933 neural crest Anatomy 0.000 description 1
- 210000001178 neural stem cell Anatomy 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 150000005480 nicotinamides Chemical class 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 102000045246 noggin Human genes 0.000 description 1
- 108700007229 noggin Proteins 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 238000000879 optical micrograph Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 1
- 239000012285 osmium tetroxide Substances 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- 210000003101 oviduct Anatomy 0.000 description 1
- PRGUDWLMFLCODA-UHFFFAOYSA-N oxybuprocaine hydrochloride Chemical compound [Cl-].CCCCOC1=CC(C(=O)OCC[NH+](CC)CC)=CC=C1N PRGUDWLMFLCODA-UHFFFAOYSA-N 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 1
- 229960001802 phenylephrine Drugs 0.000 description 1
- 210000000608 photoreceptor cell Anatomy 0.000 description 1
- 210000004694 pigment cell Anatomy 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 210000001747 pupil Anatomy 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011158 quantitative evaluation Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 108700028697 rat Erg Proteins 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000004264 retinal detachment Effects 0.000 description 1
- 230000004491 retinal development Effects 0.000 description 1
- 230000004283 retinal dysfunction Effects 0.000 description 1
- 210000001210 retinal vessel Anatomy 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 229940063122 sandimmune Drugs 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000008354 sodium chloride injection Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 231100000211 teratogenicity Toxicity 0.000 description 1
- JGVWCANSWKRBCS-UHFFFAOYSA-N tetramethylrhodamine thiocyanate Chemical compound [Cl-].C=12C=CC(N(C)C)=CC2=[O+]C2=CC(N(C)C)=CC=C2C=1C1=CC=C(SC#N)C=C1C(O)=O JGVWCANSWKRBCS-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000002691 topical anesthesia Methods 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 230000005740 tumor formation Effects 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 230000036266 weeks of gestation Effects 0.000 description 1
- 229910052724 xenon Inorganic materials 0.000 description 1
- FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- 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
- A61K35/30—Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
-
- 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
- A61K35/44—Vessels; Vascular smooth muscle cells; Endothelial cells; Endothelial progenitor cells
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
- A61K9/0051—Ocular inserts, ocular implants
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
- C12N2500/00—Specific components of cell culture medium
- C12N2500/30—Organic components
- C12N2500/38—Vitamins
-
- 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
- C12N2500/90—Serum-free medium, which may still contain naturally-sourced components
-
- 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
- C12N2500/99—Serum-free medium
-
- 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
- C12N2501/15—Transforming growth factor beta (TGF-β)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/10—Growth factors
- C12N2501/155—Bone morphogenic proteins [BMP]; Osteogenins; Osteogenic factor; Bone inducing factor
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/10—Growth factors
- C12N2501/16—Activin; Inhibin; Mullerian inhibiting substance
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/999—Small molecules not provided for elsewhere
-
- 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
- C12N2502/13—Coculture with; Conditioned medium produced by connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic fibroblasts"
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2506/00—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells
- C12N2506/02—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from embryonic cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2533/00—Supports or coatings for cell culture, characterised by material
- C12N2533/50—Proteins
- C12N2533/52—Fibronectin; Laminin
-
- 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
- C12N5/0696—Artificially induced pluripotent stem cells, e.g. iPS
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Cell Biology (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Developmental Biology & Embryology (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Ophthalmology & Optometry (AREA)
- Immunology (AREA)
- Virology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Vascular Medicine (AREA)
- Reproductive Health (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Transplantation (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Materials For Medical Uses (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US90781807P | 2007-04-18 | 2007-04-18 | |
| US907818P | 2007-04-18 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| ES2530370T3 ES2530370T3 (es) | 2015-03-02 |
| ES2530370T8 ES2530370T8 (es) | 2016-06-24 |
| ES2530370T5 true ES2530370T5 (es) | 2018-05-28 |
Family
ID=39666210
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES12181140.0T Active ES2530370T5 (es) | 2007-04-18 | 2008-04-27 | Células del epitelio pigmentario de la retina derivadas de células madre |
| ES08738258.6T Active ES2527444T5 (es) | 2007-04-18 | 2008-04-27 | Células del epitelio pigmentario de la retina derivadas de células madre |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES08738258.6T Active ES2527444T5 (es) | 2007-04-18 | 2008-04-27 | Células del epitelio pigmentario de la retina derivadas de células madre |
Country Status (9)
| Country | Link |
|---|---|
| US (3) | US8956866B2 (enExample) |
| EP (4) | EP2886646B1 (enExample) |
| JP (1) | JP5395058B2 (enExample) |
| CN (2) | CN101688178B (enExample) |
| AU (1) | AU2008242106B2 (enExample) |
| CA (1) | CA2684460C (enExample) |
| ES (2) | ES2530370T5 (enExample) |
| IL (2) | IL225163B (enExample) |
| WO (1) | WO2008129554A1 (enExample) |
Families Citing this family (80)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SG10201912182UA (en) * | 2004-01-23 | 2020-02-27 | Astellas Inst For Regenerative Medicine | Improved modalities for the treatment of degenerative diseases of the retina |
| US7794704B2 (en) | 2004-01-23 | 2010-09-14 | Advanced Cell Technology, Inc. | Methods for producing enriched populations of human retinal pigment epithelium cells for treatment of retinal degeneration |
| WO2006070370A2 (en) * | 2004-12-29 | 2006-07-06 | Hadasit Medical Research Services & Development Limited | Stem cells culture systems |
| US8597947B2 (en) | 2004-12-29 | 2013-12-03 | Hadasit Medical Research Services & Development Limited | Undifferentiated stem cell culture systems |
| JP5395058B2 (ja) | 2007-04-18 | 2014-01-22 | ハダシット メディカル リサーチ サーヴィシーズ アンド ディヴェロップメント リミテッド | 幹細胞に由来する網膜色素上皮細胞 |
| CA3177952A1 (en) * | 2007-10-12 | 2009-04-23 | Astellas Institute For Regenerative Medicine | Improved methods of producing rpe cells and compositions of rpe cells |
| CA2718904C (en) * | 2008-03-17 | 2017-01-03 | The Scripps Research Institute | Combined chemical and genetic approaches for generation of induced pluripotent stem cells |
| JPWO2009148170A1 (ja) * | 2008-06-06 | 2011-11-04 | 独立行政法人理化学研究所 | 幹細胞の培養方法 |
| CN101580816B (zh) * | 2009-04-23 | 2012-02-29 | 中国科学院广州生物医药与健康研究院 | 诱导多能性干细胞快速高效产生的新型无血清培养基以及使用其的方法 |
| CA3066806C (en) * | 2009-08-24 | 2023-03-07 | David M. Gamm | Substantially pure human retinal progenitor, forebrain progenitor, and retinal pigment epithelium cell cultures and methods of making the same |
| ES2509567T3 (es) | 2009-08-28 | 2014-10-17 | Cellular Dynamics International, Inc. | Identificación de variación genética en tejidos afectados |
| RU2409663C1 (ru) * | 2009-10-14 | 2011-01-20 | Российская Федерация, от имени которой выступает Федеральное Агентство по науке и инновациям | Способ получения дедифференцированных клеток ретинального пигментного эпителия глаза взрослого человека |
| DK2496688T3 (en) | 2009-11-05 | 2017-04-03 | Riken | Method of Inducing Differentiation in Cultured Stem Cells |
| WO2011063005A2 (en) | 2009-11-17 | 2011-05-26 | Advanced Cell Technology, Inc. | Methods of producing human rpe cells and pharmaceutical preparations of human rpe cells |
| WO2012149480A2 (en) * | 2011-04-29 | 2012-11-01 | University Of Southern California | Systems and methods for in vitro and in vivo imaging of cells on a substrate |
| EP3549617B1 (en) | 2010-07-12 | 2023-09-13 | University of Southern California | Biocompatible substrate for facilitating interconnections between stem cells and target tissues and methods for implanting same |
| EP4524568A3 (en) * | 2010-07-23 | 2025-06-18 | Astellas Institute for Regenerative Medicine | Methods for detection of rare subpopulations of cells and highly purified compositions of cells |
| FI20106354A0 (fi) * | 2010-12-20 | 2010-12-20 | Suomen Punainen Risti Veripalvelu | Menetelmä ihmisen retinan pigmentti-epiteelisolujen valmistamiseksi |
| KR101975688B1 (ko) | 2010-12-22 | 2019-05-07 | 페이트 세러퓨틱스, 인코포레이티드 | 단세포 분류 및 iPSC의 증강된 재프로그래밍을 위한 세포 배양 플랫폼 |
| US8349005B2 (en) | 2011-01-03 | 2013-01-08 | Masatoshi Murata | Method for burying implant to choroid |
| US8877489B2 (en) | 2011-12-05 | 2014-11-04 | California Institute Of Technology | Ultrathin parylene-C semipermeable membranes for biomedical applications |
| US10478206B2 (en) | 2011-04-29 | 2019-11-19 | University Of Southern California | Instruments and methods for the implantation of cell-seeded substrates |
| JP5985207B2 (ja) * | 2011-11-25 | 2016-09-06 | 住友化学株式会社 | 網膜色素上皮細胞の製造方法 |
| JP5985208B2 (ja) * | 2011-11-25 | 2016-09-06 | 住友化学株式会社 | 網膜組織の製造方法 |
| CA2856867C (en) * | 2011-11-25 | 2021-06-01 | Sumitomo Chemical Company, Limited | Methods for producing retinal tissue and retina-related cell |
| JP6067232B2 (ja) * | 2011-11-25 | 2017-01-25 | 住友化学株式会社 | 網膜層特異的神経細胞を製造する方法 |
| JP5985209B2 (ja) * | 2011-11-25 | 2016-09-06 | 住友化学株式会社 | 眼杯様構造体の製造方法 |
| US9248013B2 (en) | 2011-12-05 | 2016-02-02 | California Institute Of Technology | 3-Dimensional parylene scaffold cage |
| US9658216B2 (en) | 2012-01-31 | 2017-05-23 | Cell Cure Neurosciences Ltd. | Methods of selecting retinal pigmented epithelial cells |
| RU2486603C1 (ru) * | 2012-04-11 | 2013-06-27 | Федеральное государственное бюджетное учреждение науки Институт биологии развития им. Н.К. Кольцова РАН (ИБР РАН) | Способ моделирования тканевой структуры сетчатки глаза человека |
| CN103627669A (zh) * | 2012-08-22 | 2014-03-12 | 复旦大学 | 一种诱导人多能干细胞分化为视网膜前体细胞的方法 |
| US9265458B2 (en) | 2012-12-04 | 2016-02-23 | Sync-Think, Inc. | Application of smooth pursuit cognitive testing paradigms to clinical drug development |
| AU2014212230B2 (en) | 2013-02-01 | 2019-07-04 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Method for generating retinal pigment epithelium (RPE) cells from induced pluripotent stem cells (iPSCs) |
| US9380976B2 (en) | 2013-03-11 | 2016-07-05 | Sync-Think, Inc. | Optical neuroinformatics |
| AU2014246962A1 (en) * | 2013-04-03 | 2015-11-19 | Tampereen Yliopisto | Methods and media for differentiating eye cells |
| CA2920600C (en) | 2013-08-06 | 2023-11-28 | Riken | Method for producing anterior eye segment tissue |
| EP3656853B1 (en) | 2013-08-23 | 2023-02-15 | Sumitomo Chemical Company, Limited | Method for producing retinal tissue and retina-related cells |
| US11492593B2 (en) * | 2013-10-09 | 2022-11-08 | Healios K.K. | Method for purification of retinal pigment epithelial cells |
| AU2014345110B2 (en) * | 2013-11-11 | 2021-01-14 | Riken | Method for producing retinal pigment epithelial cells |
| US20150148383A1 (en) * | 2013-11-22 | 2015-05-28 | Regenerative Research Foundation | Methods for Inhibiting or Reversing Epiretinal Membrane Formation |
| WO2015087231A1 (en) * | 2013-12-11 | 2015-06-18 | Pfizer Limited | Method for producing retinal pigment epithelial cells |
| KR102670874B1 (ko) | 2014-03-04 | 2024-05-31 | 페이트 세러퓨틱스, 인코포레이티드 | 개선된 재프로그래밍 방법 및 세포 배양 플랫폼 |
| US20170080030A1 (en) * | 2014-03-17 | 2017-03-23 | University Of Virginia Patent Foundation | Compositions and methods for treating retinopathy |
| WO2015175504A1 (en) * | 2014-05-12 | 2015-11-19 | The Johns Hopkins University | Differentiation of human pluripotent stem cells into retinal pigment epithelium using hif1 inhibitors |
| AU2015336453B2 (en) | 2014-10-24 | 2021-05-20 | Riken | Production method for nerve tissue |
| EP3211071B1 (en) | 2014-10-24 | 2021-05-05 | Sumitomo Dainippon Pharma Co., Ltd. | Production method for retinal tissue |
| KR102728629B1 (ko) | 2014-12-18 | 2024-11-12 | 쏘흐본느 유니베흐시테 | 망막 변성의 치료를 위한 otx2를 과발현하는 형질전환 rpe 세포 |
| EP3240890B1 (en) * | 2014-12-30 | 2021-06-16 | Cell Cure Neurosciences Ltd. | Assessing retinal pigment epithelial cell populations |
| IL273405B2 (en) * | 2014-12-30 | 2024-01-01 | Cell Cure Neurosciences Ltd | Rpe cell populations and methods of generating same |
| CA2972700A1 (en) | 2014-12-30 | 2016-07-07 | Cell Cure Neurosciences Ltd. | Methods of treating retinal diseases |
| US11230696B2 (en) | 2015-07-29 | 2022-01-25 | Hadasit Medical Research Services And Development Ltd. | Large scale production of retinal pigment epithelial cells |
| WO2017021973A1 (en) | 2015-08-05 | 2017-02-09 | Cell Cure Neurosciences Ltd. | Preparation of retinal pigment epithelium cells |
| WO2017021972A1 (en) | 2015-08-05 | 2017-02-09 | Cell Cure Neurosciences Ltd. | Preparation of photoreceptors for the treatment of retinal diseases |
| ES2971677T3 (es) * | 2015-09-08 | 2024-06-06 | Sumitomo Pharma Co Ltd | Método para la producción de tejido retiniano |
| CN105112368B (zh) * | 2015-09-30 | 2018-09-21 | 奥思达干细胞有限公司 | 一种治疗视网膜变性的干细胞制剂及其使用方法 |
| EP3362570A4 (en) | 2015-10-16 | 2019-03-20 | Fate Therapeutics, Inc. | PLATFORM FOR THE INDUCTION AND MAINTENANCE OF BASIC STATUS PLURIPOTENCE |
| US12188047B2 (en) * | 2015-10-26 | 2025-01-07 | Hadasit Medical Research Services And Development Ltd. | Preparation of retinal pigment epithelium cells |
| CH711966A2 (it) * | 2015-12-23 | 2017-06-30 | Pinelli Roberto | Cellule staminali retinali. |
| CN109312306B (zh) | 2016-04-22 | 2023-05-09 | 住友制药株式会社 | 产生视网膜组织的方法 |
| KR20190093199A (ko) | 2016-12-07 | 2019-08-08 | 메이오 파운데이션 포 메디칼 에쥬케이션 앤드 리써치 | 망막 색소 상피 이식을 위해 피브린 지지체를 사용하는 방법 및 물질 |
| CN106754718A (zh) * | 2016-12-19 | 2017-05-31 | 胡其锐 | 一种人胚胎干细胞快速定向分化至视网膜色素上皮细胞的方法 |
| US12281328B2 (en) | 2017-02-08 | 2025-04-22 | Hadasit Medical Research Services And Development Ltd. | Photoreceptor cells for the treatment of retinal diseases |
| US20200085882A1 (en) | 2017-03-16 | 2020-03-19 | Lineage Cell Therapeutics, Inc. | Methods for measuring therapeutic effects of retinal disease therapies |
| CN108728413A (zh) * | 2017-06-13 | 2018-11-02 | 中山大学中山眼科中心 | 一种人多能干细胞来源人视网膜色素上皮细胞的制备和扩增培养方法 |
| WO2019069327A1 (en) | 2017-10-05 | 2019-04-11 | Eyestem Research Private Limited | UNIFIED CELL DIFFERENTIATION PROTOCOL |
| JP7287948B2 (ja) | 2018-03-22 | 2023-06-06 | オリエンタル酵母工業株式会社 | 多分化能性幹細胞分化促進剤 |
| CN108531443A (zh) * | 2018-04-04 | 2018-09-14 | 温州医科大学附属第二医院、温州医科大学附属育英儿童医院 | 小分子诱导多能性干细胞分化为视网膜色素上皮细胞的方法 |
| CN110205283B (zh) * | 2018-04-18 | 2021-04-23 | 浙江大学 | 一种诱导人羊膜上皮细胞向视网膜色素上皮细胞分化的方法及其应用 |
| WO2019204817A1 (en) | 2018-04-20 | 2019-10-24 | FUJIFILM Cellular Dynamics, Inc. | Method for differentiation of ocular cells and use thereof |
| JP2022532411A (ja) * | 2019-05-15 | 2022-07-14 | ノヴォ ノルディスク アー／エス | ヒト多能性幹細胞から眼野前駆細胞を得るための方法 |
| EP3754014A1 (en) | 2019-06-21 | 2020-12-23 | Centre d'Etude des Cellules Souches (CECS) | Automated method for preparing retinal pigment epithelium cells |
| AU2021280260A1 (en) * | 2020-05-25 | 2023-02-02 | Hadasit Medical Research Services And Development Ltd. | Methods and compositions for treating retinal diseases and conditions |
| AU2021280343A1 (en) * | 2020-05-29 | 2022-12-08 | FUJIFILM Cellular Dynamics, Inc. | Retinal pigmented epithelium and photoreceptor dual cell aggregates and methods of use thereof |
| JP2024522608A (ja) | 2021-06-09 | 2024-06-21 | リネージ セル セラピューティクス インコーポレイテッド | 網膜の疾患および症状を処置するための方法および組成物 |
| EP4377445A1 (en) | 2021-07-28 | 2024-06-05 | Lineage Cell Therapeutics, Inc. | Expansion of retinal pigment epithelium cells |
| CN119384700A (zh) | 2022-04-15 | 2025-01-28 | 艾斯本神经科学公司 | 细胞分化状态的分类方法和分化细胞的相关组合物 |
| CN115840045B (zh) * | 2023-02-23 | 2023-04-28 | 中国农业大学 | 一种猪胚胎期毛囊基板前体细胞的鉴定方法及其应用 |
| WO2025083169A1 (en) | 2023-10-17 | 2025-04-24 | Tenpoint Therapeutics Limited | Combination of a vegf inhibitor and a complement pathway inhibitor for treating ocular disorders |
| WO2025096328A1 (en) * | 2023-10-30 | 2025-05-08 | The Jackson Laboratory | Cell therapies for retinal diseases |
| CN119709618B (zh) * | 2024-12-25 | 2025-10-28 | 电子科技大学附属医院·四川省人民医院 | 一种从iPSC分化的细胞中分选成熟RPE细胞的方法及其应用 |
Family Cites Families (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SG49267A1 (en) | 1989-08-14 | 1998-05-18 | Photogenesis Inc | Surgical instrument and cell isolation and transplantation |
| US5750342A (en) * | 1990-06-11 | 1998-05-12 | Nexstar Pharmaceuticals, Inc. | Nucleic acid ligands of tissue target |
| TW209224B (enExample) * | 1991-05-27 | 1993-07-11 | Yoshitomi Pharmaceutical | |
| US6045791A (en) * | 1992-03-06 | 2000-04-04 | Photogenesis, Inc. | Retinal pigment epithelium transplantation |
| DE4219250A1 (de) * | 1992-06-12 | 1993-12-16 | Behringwerke Ag | Serum-freies Zellkulturmedium |
| ATE196923T1 (de) * | 1993-04-30 | 2000-10-15 | Photogenesis Inc | Transplantation des retinalen pigmentepithels |
| US5755785A (en) | 1994-08-12 | 1998-05-26 | The University Of South Florida | Sutureless corneal transplantation method |
| US5843780A (en) | 1995-01-20 | 1998-12-01 | Wisconsin Alumni Research Foundation | Primate embryonic stem cells |
| US5941250A (en) | 1996-11-21 | 1999-08-24 | University Of Louisville Research Foundation Inc. | Retinal tissue implantation method |
| GB9715584D0 (en) | 1997-07-23 | 1997-10-01 | Eisai Co Ltd | Compounds |
| JP3663990B2 (ja) | 1999-08-31 | 2005-06-22 | 不二製油株式会社 | 含気チョコレート及びその製造法 |
| GB0001930D0 (en) | 2000-01-27 | 2000-03-22 | Novartis Ag | Organic compounds |
| WO2001098463A1 (en) | 2000-06-20 | 2001-12-27 | Es Cell International Pte Ltd | Method of controlling differentiation of embryonic stem (es) cells by culturing es cells in the presence of bmp-2 pathway antagonists |
| CA2436535A1 (en) | 2001-01-31 | 2002-08-08 | Prizer Products Inc. | Nicotinamide biaryl derivatives useful as inhibitors of pde4 isozymes |
| AU2003202988A1 (en) * | 2002-01-14 | 2003-07-30 | The Board Of Trustees Of The University Of Illinois | Use of modified pyrimidine compounds to promote stem cell migration and proliferation |
| AU2003201745A1 (en) | 2002-02-11 | 2003-09-04 | Pfizer Limited | Nicotinamide derivatives and a tiotropium salt in combination for the treatment of e.g. inflammatory, allergic and respiratory diseases |
| US7288658B2 (en) | 2003-07-15 | 2007-10-30 | Hoffmann-La Roche Inc. | Process for preparation of pyridine derivatives |
| US20050019718A1 (en) | 2003-07-22 | 2005-01-27 | Hanson G. Herbert | Orthodontic devices for use with arch wires |
| SG10201912182UA (en) * | 2004-01-23 | 2020-02-27 | Astellas Inst For Regenerative Medicine | Improved modalities for the treatment of degenerative diseases of the retina |
| US7794704B2 (en) * | 2004-01-23 | 2010-09-14 | Advanced Cell Technology, Inc. | Methods for producing enriched populations of human retinal pigment epithelium cells for treatment of retinal degeneration |
| DE102004048640A1 (de) * | 2004-10-04 | 2006-04-06 | Otmar Fahrion | Kette |
| JP2006113175A (ja) * | 2004-10-13 | 2006-04-27 | Konica Minolta Opto Inc | 光学フィルム、偏光板及び表示装置 |
| WO2006070370A2 (en) | 2004-12-29 | 2006-07-06 | Hadasit Medical Research Services & Development Limited | Stem cells culture systems |
| JP5395058B2 (ja) | 2007-04-18 | 2014-01-22 | ハダシット メディカル リサーチ サーヴィシーズ アンド ディヴェロップメント リミテッド | 幹細胞に由来する網膜色素上皮細胞 |
| CN102334251B (zh) | 2009-02-25 | 2013-05-29 | 皇家飞利浦电子股份有限公司 | 利用光子冷却依存激光器电压用于激光二极管的输出功率稳定 |
| CN105814192A (zh) * | 2013-10-09 | 2016-07-27 | 加利福尼亚大学董事会 | 哺乳动物视网膜干细胞产生方法和应用 |
-
2008
- 2008-04-27 JP JP2010503665A patent/JP5395058B2/ja active Active
- 2008-04-27 CA CA2684460A patent/CA2684460C/en active Active
- 2008-04-27 EP EP14193621.1A patent/EP2886646B1/en active Active
- 2008-04-27 EP EP19191405.0A patent/EP3640326A1/en not_active Withdrawn
- 2008-04-27 CN CN2008800207480A patent/CN101688178B/zh active Active
- 2008-04-27 AU AU2008242106A patent/AU2008242106B2/en active Active
- 2008-04-27 ES ES12181140.0T patent/ES2530370T5/es active Active
- 2008-04-27 CN CN201310484803.4A patent/CN103555654B/zh active Active
- 2008-04-27 EP EP12181140.0A patent/EP2554661B2/en active Active
- 2008-04-27 EP EP08738258.6A patent/EP2147094B2/en active Active
- 2008-04-27 ES ES08738258.6T patent/ES2527444T5/es active Active
- 2008-04-27 WO PCT/IL2008/000556 patent/WO2008129554A1/en not_active Ceased
- 2008-04-27 US US12/450,943 patent/US8956866B2/en active Active
-
2013
- 2013-03-11 IL IL225163A patent/IL225163B/en active IP Right Grant
-
2014
- 2014-12-29 US US14/583,838 patent/US20150125506A1/en not_active Abandoned
- 2014-12-29 US US14/583,848 patent/US20150118749A1/en not_active Abandoned
-
2017
- 2017-12-26 IL IL256587A patent/IL256587B/en active IP Right Grant
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2530370T5 (es) | Células del epitelio pigmentario de la retina derivadas de células madre | |
| US20230028133A1 (en) | Methods of treating retinal diseases | |
| ES2774456T3 (es) | Poblaciones de células del RPE y métodos de generación de las mismas | |
| JP2023089154A (ja) | 網膜疾患治療法の治療効果を測定する方法 | |
| ES2880346T3 (es) | Evaluación de poblaciones de células epiteliales de pigmento retiniano | |
| HK1179647B (en) | Stem cell-derived retinal pigment epithelial cells | |
| HK1211619B (en) | Stem cell-derived retinal pigment epithelial cells | |
| HK1140791B (en) | Stem cell-derived retinal pigment epithelial cells | |
| IL201600A (en) | Method of generating pluripotent stem cell derived retinal pigment epithelial cells | |
| HK1191377B (en) | Stem cell-derived retinal pigment epithelial cells |