Delivery of Human iPSC‐Derived RPE Cells in Healthy Minipig Retina Results in Interaction Between Photoreceptors and Transplanted Cells
Abstract In late stages of inherited and acquired retinal diseases such as Stargardt disease (STGD) or dry age‐related macular degeneration (AMD), loss of retinal pigment epithelia (RPE) cells and subsequently photoreceptors in the macular area result in a dramatic decline of central visual function...
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Wiley
2025-05-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202412301 |
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| author | Anna Macečková Brymová Francisco Javier Rodriguez‐Jimenez Annika Konrad Yaroslav Nemesh Muhammed Arshad Thottappali Ana Artero‐Castro Ruslan Nyshchuk Anastasiia Kolesnikova Brigitte Müller Hana Studenovska Jana Juhasova Stefan Juhas Ivona Valekova Dunja Lukovic Claudia Aleman Taras Ardan Saskia Drutovič Jan Motlik Zdenka Ellederova Zbinek Straňák Miroslav Veith Lyubomyr Lytvynchuk Ruchi Sharma Kapil Bharti Goran Petrovski Pavla Jendelova Knut Stieger Slaven Erceg |
| author_facet | Anna Macečková Brymová Francisco Javier Rodriguez‐Jimenez Annika Konrad Yaroslav Nemesh Muhammed Arshad Thottappali Ana Artero‐Castro Ruslan Nyshchuk Anastasiia Kolesnikova Brigitte Müller Hana Studenovska Jana Juhasova Stefan Juhas Ivona Valekova Dunja Lukovic Claudia Aleman Taras Ardan Saskia Drutovič Jan Motlik Zdenka Ellederova Zbinek Straňák Miroslav Veith Lyubomyr Lytvynchuk Ruchi Sharma Kapil Bharti Goran Petrovski Pavla Jendelova Knut Stieger Slaven Erceg |
| author_sort | Anna Macečková Brymová |
| collection | DOAJ |
| description | Abstract In late stages of inherited and acquired retinal diseases such as Stargardt disease (STGD) or dry age‐related macular degeneration (AMD), loss of retinal pigment epithelia (RPE) cells and subsequently photoreceptors in the macular area result in a dramatic decline of central visual function. Repopulating this area with functional RPE cells may prevent or decline the progression of photoreceptor loss. In the present study, the viability, survival, and integration of human induced pluripotent stem cell (hiPSC)‐derived RPE cells (hiPSC‐RPE) is assessed generated using clinical‐grade protocol and cultured on a clinically relevant scaffold (poly‐L‐lactide‐co‐D, L‐lactide, PDLLA) after subretinal implantation in immunosuppressed minipigs for up to 6 weeks. It is shown that transplanted hiPSC‐RPE cells maintain the RPE cell features such as cell polarity, hexagonal shape, and cell–cell contacts, and interact closely with photoreceptor outer segments without signs of gliosis or neuroinflammation throughout the entire period of examination. In addition, an efficient immunosuppressing strategy with a continuous supply of tacrolimus is applied. Continuous verification and improvement of existing protocols are crucial for its translation to the clinic. The results support the use of hiPSC‐RPE on PDLLA scaffold as a cell replacement therapeutic approach for RPE degenerative diseases. |
| format | Article |
| id | doaj-art-74e6dc3e8b484f04929d46c3f98202ff |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-74e6dc3e8b484f04929d46c3f98202ff2025-08-20T02:34:43ZengWileyAdvanced Science2198-38442025-05-011220n/an/a10.1002/advs.202412301Delivery of Human iPSC‐Derived RPE Cells in Healthy Minipig Retina Results in Interaction Between Photoreceptors and Transplanted CellsAnna Macečková Brymová0Francisco Javier Rodriguez‐Jimenez1Annika Konrad2Yaroslav Nemesh3Muhammed Arshad Thottappali4Ana Artero‐Castro5Ruslan Nyshchuk6Anastasiia Kolesnikova7Brigitte Müller8Hana Studenovska9Jana Juhasova10Stefan Juhas11Ivona Valekova12Dunja Lukovic13Claudia Aleman14Taras Ardan15Saskia Drutovič16Jan Motlik17Zdenka Ellederova18Zbinek Straňák19Miroslav Veith20Lyubomyr Lytvynchuk21Ruchi Sharma22Kapil Bharti23Goran Petrovski24Pavla Jendelova25Knut Stieger26Slaven Erceg27Institute of Animal Physiology and Genetics Czech Academy of Sciences Libechov 27721 Czech RepublicStem Cell Therapies in Neurodegenerative Diseases Lab Centro de Investigación Príncipe Felipe Valencia 46012 SpainDepartment of Ophthalmology Justus‐Liebig‐University Giessen 35390 Giessen GermanyInstitute of Animal Physiology and Genetics Czech Academy of Sciences Libechov 27721 Czech RepublicInstitute of Macromolecular Chemistry Czech Academy of Sciences Prague 16200 Czech RepublicStem Cell Therapies in Neurodegenerative Diseases Lab Centro de Investigación Príncipe Felipe Valencia 46012 SpainInstitute of Animal Physiology and Genetics Czech Academy of Sciences Libechov 27721 Czech RepublicInstitute of Animal Physiology and Genetics Czech Academy of Sciences Libechov 27721 Czech RepublicDepartment of Ophthalmology Justus‐Liebig‐University Giessen 35390 Giessen GermanyInstitute of Macromolecular Chemistry Czech Academy of Sciences Prague 16200 Czech RepublicInstitute of Animal Physiology and Genetics Czech Academy of Sciences Libechov 27721 Czech RepublicInstitute of Animal Physiology and Genetics Czech Academy of Sciences Libechov 27721 Czech RepublicInstitute of Animal Physiology and Genetics Czech Academy of Sciences Libechov 27721 Czech RepublicRetinal degeneration Lab Department of Animal Production and Health Public Veterinary Health and Food Science and Technology School of Veterinary Medicine Universidad Cardenal Herrera‐CEU, CEU Universities Alfara del Patriarca 46115 SpainStem Cell Therapies in Neurodegenerative Diseases Lab Centro de Investigación Príncipe Felipe Valencia 46012 SpainInstitute of Animal Physiology and Genetics Czech Academy of Sciences Libechov 27721 Czech RepublicInstitute of Animal Physiology and Genetics Czech Academy of Sciences Libechov 27721 Czech RepublicInstitute of Animal Physiology and Genetics Czech Academy of Sciences Libechov 27721 Czech RepublicInstitute of Animal Physiology and Genetics Czech Academy of Sciences Libechov 27721 Czech Republic3rd Faculty of Medicine Charles University in Prague, Vinohrady Teaching Hospital Department of Ophthalmology Prague 10034 Czech Republic3rd Faculty of Medicine Charles University in Prague, Vinohrady Teaching Hospital Department of Ophthalmology Prague 10034 Czech RepublicDepartment of Ophthalmology Justus‐Liebig‐University Giessen 35390 Giessen GermanyOcular and Stem Cell Translational Research Section National Eye Institute NIH Bethesda MD 20892 USAOcular and Stem Cell Translational Research Section National Eye Institute NIH Bethesda MD 20892 USADepartment of Ophthalmology Center for Eye Research Oslo University Hospital and University of Oslo Oslo 0192 NorwayInstitute of Experimental Medicine Czech Academy of Sciences Department of Neuroregeneration Prague 14220 Czech RepublicDepartment of Ophthalmology Justus‐Liebig‐University Giessen 35390 Giessen GermanyStem Cell Therapies in Neurodegenerative Diseases Lab Centro de Investigación Príncipe Felipe Valencia 46012 SpainAbstract In late stages of inherited and acquired retinal diseases such as Stargardt disease (STGD) or dry age‐related macular degeneration (AMD), loss of retinal pigment epithelia (RPE) cells and subsequently photoreceptors in the macular area result in a dramatic decline of central visual function. Repopulating this area with functional RPE cells may prevent or decline the progression of photoreceptor loss. In the present study, the viability, survival, and integration of human induced pluripotent stem cell (hiPSC)‐derived RPE cells (hiPSC‐RPE) is assessed generated using clinical‐grade protocol and cultured on a clinically relevant scaffold (poly‐L‐lactide‐co‐D, L‐lactide, PDLLA) after subretinal implantation in immunosuppressed minipigs for up to 6 weeks. It is shown that transplanted hiPSC‐RPE cells maintain the RPE cell features such as cell polarity, hexagonal shape, and cell–cell contacts, and interact closely with photoreceptor outer segments without signs of gliosis or neuroinflammation throughout the entire period of examination. In addition, an efficient immunosuppressing strategy with a continuous supply of tacrolimus is applied. Continuous verification and improvement of existing protocols are crucial for its translation to the clinic. The results support the use of hiPSC‐RPE on PDLLA scaffold as a cell replacement therapeutic approach for RPE degenerative diseases.https://doi.org/10.1002/advs.202412301age‐related macular degenerationcell therapyHuman induced pluripotent stem cells;minipigsretinaretinal degenerationretinal pigment epithelium |
| spellingShingle | Anna Macečková Brymová Francisco Javier Rodriguez‐Jimenez Annika Konrad Yaroslav Nemesh Muhammed Arshad Thottappali Ana Artero‐Castro Ruslan Nyshchuk Anastasiia Kolesnikova Brigitte Müller Hana Studenovska Jana Juhasova Stefan Juhas Ivona Valekova Dunja Lukovic Claudia Aleman Taras Ardan Saskia Drutovič Jan Motlik Zdenka Ellederova Zbinek Straňák Miroslav Veith Lyubomyr Lytvynchuk Ruchi Sharma Kapil Bharti Goran Petrovski Pavla Jendelova Knut Stieger Slaven Erceg Delivery of Human iPSC‐Derived RPE Cells in Healthy Minipig Retina Results in Interaction Between Photoreceptors and Transplanted Cells Advanced Science age‐related macular degeneration cell therapy Human induced pluripotent stem cells;minipigs retina retinal degeneration retinal pigment epithelium |
| title | Delivery of Human iPSC‐Derived RPE Cells in Healthy Minipig Retina Results in Interaction Between Photoreceptors and Transplanted Cells |
| title_full | Delivery of Human iPSC‐Derived RPE Cells in Healthy Minipig Retina Results in Interaction Between Photoreceptors and Transplanted Cells |
| title_fullStr | Delivery of Human iPSC‐Derived RPE Cells in Healthy Minipig Retina Results in Interaction Between Photoreceptors and Transplanted Cells |
| title_full_unstemmed | Delivery of Human iPSC‐Derived RPE Cells in Healthy Minipig Retina Results in Interaction Between Photoreceptors and Transplanted Cells |
| title_short | Delivery of Human iPSC‐Derived RPE Cells in Healthy Minipig Retina Results in Interaction Between Photoreceptors and Transplanted Cells |
| title_sort | delivery of human ipsc derived rpe cells in healthy minipig retina results in interaction between photoreceptors and transplanted cells |
| topic | age‐related macular degeneration cell therapy Human induced pluripotent stem cells;minipigs retina retinal degeneration retinal pigment epithelium |
| url | https://doi.org/10.1002/advs.202412301 |
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