ES2527444T5 - Células del epitelio pigmentario de la retina derivadas de células madre - Google Patents
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- ES2527444T5 ES2527444T5 ES08738258.6T ES08738258T ES2527444T5 ES 2527444 T5 ES2527444 T5 ES 2527444T5 ES 08738258 T ES08738258 T ES 08738258T ES 2527444 T5 ES2527444 T5 ES 2527444T5
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Families Citing this family (80)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| EP2929782A1 (en) | 2004-01-23 | 2015-10-14 | Ocata Therapeutics, Inc. | Improved modalities for the treatment of degenerative diseases of the retina |
| US8597947B2 (en) | 2004-12-29 | 2013-12-03 | Hadasit Medical Research Services & Development Limited | Undifferentiated stem cell culture systems |
| EP2410043A3 (en) * | 2004-12-29 | 2013-01-23 | Hadasit Medical Research Services And Development Ltd. | Stem cells culture systems |
| CN101688178B (zh) | 2007-04-18 | 2013-12-04 | 哈达锡特医学研究服务及发展有限公司 | 干细胞衍生的视网膜色素上皮细胞 |
| DK2209888T3 (da) * | 2007-10-12 | 2020-01-20 | Astellas Inst For Regenerative Medicine | Forbedrede fremgangsmåder til fremstilling af rpe-celler og sammensætninger af rpe-celler |
| US9534205B2 (en) | 2008-03-17 | 2017-01-03 | The Scripps Research Institute | Combined chemical and genetic approaches for generation of induced pluripotent stem cells |
| US10227563B2 (en) * | 2008-06-06 | 2019-03-12 | Riken | Method for culture of stem cell |
| 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 |
| JP5885255B2 (ja) | 2009-08-28 | 2016-03-15 | セルラー ダイナミクス インターナショナル， インコーポレイテッド | 罹患組織における遺伝的変異の同定 |
| 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 |
| ES2619564T3 (es) | 2009-11-05 | 2017-06-26 | Riken | Un método de inducción de diferenciación de células madre cultivadas |
| 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 |
| 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 |
| US9089600B2 (en) * | 2010-07-12 | 2015-07-28 | University Of Southern California | Systems and methods for in vitro and in vivo imaging of cells on a substrate |
| WO2012012803A2 (en) * | 2010-07-23 | 2012-01-26 | Advanced Cell Technology, Inc. | 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 |
| KR102482184B1 (ko) | 2010-12-22 | 2022-12-28 | 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 |
| WO2012149468A2 (en) | 2011-04-29 | 2012-11-01 | University Of Southern California | Instruments and methods for the implantation of cell-seeded substrates |
| 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 |
| ES2733956T3 (es) | 2011-11-25 | 2019-12-03 | Sumitomo Chemical Co | Métodos para producir tejido retiniano y células relacionadas con la retina |
| 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 |
| 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 |
| 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 |
| US9248013B2 (en) | 2011-12-05 | 2016-02-02 | California Institute Of Technology | 3-Dimensional parylene scaffold cage |
| AU2013216382B2 (en) * | 2012-01-31 | 2018-08-02 | Hadasit Medical Research Services And Development 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 |
| US20150368713A1 (en) | 2013-02-01 | 2015-12-24 | THE UNITED STATES OF AMERICAN, as represented by the Secretary, Department of Health and Human Serv | 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 |
| CA2914286A1 (en) * | 2013-04-03 | 2014-10-09 | 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 |
| AU2014309730B2 (en) | 2013-08-23 | 2020-11-19 | Riken | Method for producing retinal tissue and retina-related cells |
| CN105829526A (zh) * | 2013-10-09 | 2016-08-03 | 希里欧斯株式会社 | 用于纯化视网膜色素上皮细胞的方法 |
| JP6495176B2 (ja) * | 2013-11-11 | 2019-04-03 | 住友化学株式会社 | 網膜色素上皮細胞の製造方法 |
| US20150148383A1 (en) * | 2013-11-22 | 2015-05-28 | Regenerative Research Foundation | Methods for Inhibiting or Reversing Epiretinal Membrane Formation |
| CN105814194A (zh) * | 2013-12-11 | 2016-07-27 | 辉瑞有限公司 | 产生视网膜色素上皮细胞的方法 |
| KR20240091064A (ko) | 2014-03-04 | 2024-06-21 | 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 |
| US11214772B2 (en) | 2014-10-24 | 2022-01-04 | Sumitomo Dainippon Pharma Co., Ltd. | Production method for retinal tissue |
| AU2015336453B2 (en) | 2014-10-24 | 2021-05-20 | Riken | Production method for nerve tissue |
| KR102728629B1 (ko) * | 2014-12-18 | 2024-11-12 | 쏘흐본느 유니베흐시테 | 망막 변성의 치료를 위한 otx2를 과발현하는 형질전환 rpe 세포 |
| KR20170115514A (ko) * | 2014-12-30 | 2017-10-17 | 셀 큐어 뉴로사이언시스 리미티드 | Rpe 세포 집단 및 이를 생성하는 방법 |
| EP3916085A1 (en) | 2014-12-30 | 2021-12-01 | Cell Cure Neurosciences Ltd. | Assessing retinal pigment epithelial cell populations |
| MX2017008818A (es) | 2014-12-30 | 2018-03-14 | Cell Cure Neurosciences Ltd | Metodos para tratar enfermedades de la retina. |
| ES2865024T3 (es) | 2015-07-29 | 2021-10-14 | Hadasit Med Res Service | Producción a gran escala de células de epitelio pigmentario retiniano |
| US11090337B2 (en) | 2015-08-05 | 2021-08-17 | Cell Cure Neurosciences Ltd | Preparation of photoreceptors for the treatment of retinal diseases |
| WO2017021973A1 (en) | 2015-08-05 | 2017-02-09 | Cell Cure Neurosciences Ltd. | Preparation of retinal pigment epithelium cells |
| US12385008B2 (en) | 2015-09-08 | 2025-08-12 | Sumitomo Pharma Co., Ltd. | Method for producing retinal tissue |
| 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 |
| US11441126B2 (en) | 2015-10-16 | 2022-09-13 | Fate Therapeutics, Inc. | Platform for the induction and maintenance of ground state pluripotency |
| ES3018474T3 (es) | 2015-10-26 | 2025-05-16 | Cell Cure Neurosciences Ltd | Preparación de células del epitelio pigmentario de la retina |
| CH711966A2 (it) * | 2015-12-23 | 2017-06-30 | Pinelli Roberto | Cellule staminali retinali. |
| AU2017254264C1 (en) | 2016-04-22 | 2023-10-05 | Riken | Method for producing retinal tissue |
| FI3551216T3 (fi) | 2016-12-07 | 2024-10-14 | Mayo Found Medical Education & Res | Menetelmät ja materiaalit fibriinitukien käyttämiseksi verkkokalvon pigmenttiepiteelin siirroissa |
| 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 |
| AU2018217992B2 (en) * | 2017-02-08 | 2023-12-14 | Hadasit Medical Research Services And Development Ltd. | Photoreceptor cells for the treatment of retinal diseases |
| KR20200031559A (ko) | 2017-03-16 | 2020-03-24 | 리니지 셀 테라퓨틱스, 인크. | 망막 질환 요법의 치료 효과를 측정하는 방법 |
| 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 |
| EP3770250A4 (en) | 2018-03-22 | 2021-11-24 | Oriental Yeast Co., Ltd. | DIFFERENTIATION PROMOTER FOR PLURIPOTENT STEM CELLS |
| 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 |
| CA3097428A1 (en) | 2018-04-20 | 2019-10-24 | FUJIFILM Cellular Dynamics, Inc. | Method for differentiation of ocular cells and use thereof |
| CN113811605B (zh) * | 2019-05-15 | 2024-09-27 | 诺和诺德股份有限公司 | 从人多能干细胞获得眼野祖细胞的方法 |
| EP3754014A1 (en) | 2019-06-21 | 2020-12-23 | Centre d'Etude des Cellules Souches (CECS) | Automated method for preparing retinal pigment epithelium cells |
| IL298569A (en) * | 2020-05-25 | 2023-01-01 | Lineage Cell Therapeutics Inc | Methods and compositions for treating retinal diseases and conditions |
| BR112022024031A2 (pt) * | 2020-05-29 | 2023-01-31 | Fujifilm Cellular Dynamics Inc | Agregados de células duplas de epitélio pigmentado da retina e fotorreceptor, e métodos de uso dos mesmos |
| TWI853255B (zh) | 2021-06-09 | 2024-08-21 | 美商譜系細胞治療公司 | 治療視網膜疾病及病況之方法及組成物 |
| CN117957311A (zh) | 2021-07-28 | 2024-04-30 | 谱系细胞疗法公司 | 视网膜色素上皮细胞的扩增 |
| WO2023201361A1 (en) | 2022-04-15 | 2023-10-19 | Aspen Neuroscience, Inc. | Methods of classifying the differentiation state of cells and related compositions of differentiated cells |
| 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 |
| JP3490447B2 (ja) * | 1993-04-30 | 2004-01-26 | フォトジェネシス インコーポレイテッド | 網膜色素上皮移植 |
| 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 |
| CA2411914C (en) | 2000-06-20 | 2012-08-21 | 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 |
| PL364135A1 (en) | 2001-01-31 | 2004-12-13 | Pfizer Products Inc. | Nicotinamide biaryl derivatives useful as inhibitors of pde4 isozymes |
| WO2003060085A2 (en) * | 2002-01-14 | 2003-07-24 | The Board Of Trustees Of The University Of Illinois | Mammalian neural stem cells, compositions and uses thereof |
| 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 |
| 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 |
| EP2929782A1 (en) * | 2004-01-23 | 2015-10-14 | Ocata Therapeutics, Inc. | Improved modalities for the treatment of degenerative diseases of the retina |
| 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 |
| EP2410043A3 (en) * | 2004-12-29 | 2013-01-23 | Hadasit Medical Research Services And Development Ltd. | Stem cells culture systems |
| CN101688178B (zh) | 2007-04-18 | 2013-12-04 | 哈达锡特医学研究服务及发展有限公司 | 干细胞衍生的视网膜色素上皮细胞 |
| EP2401794B1 (en) | 2009-02-25 | 2012-09-05 | Philips Intellectual Property & Standards GmbH | Output power stabilization for laser diodes using the photon-cooling dependent laser voltage |
| EP3047017B1 (en) * | 2013-10-09 | 2025-09-10 | The Regents of the University of California | Methods of mammalian retinal stem cell production and applications |
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- 2008-04-27 EP EP08738258.6A patent/EP2147094B2/en active Active
- 2008-04-27 JP JP2010503665A patent/JP5395058B2/ja 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 EP14193621.1A patent/EP2886646B1/en active Active
- 2008-04-27 ES ES08738258.6T patent/ES2527444T5/es active Active
- 2008-04-27 ES ES12181140.0T patent/ES2530370T5/es active Active
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2013
- 2013-03-11 IL IL225163A patent/IL225163B/en active IP Right Grant
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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
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2017
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