{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:35:34Z","timestamp":1792794934864,"version":"4.5.0"},"reference-count":115,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T00:00:00Z","timestamp":1689552000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001824","name":"Czech Science Foundation","doi-asserted-by":"publisher","award":["18-04393S"],"award-info":[{"award-number":["18-04393S"]}],"id":[{"id":"10.13039\/501100001824","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Norway Grants and Technology Agency of the Czech Republic","award":["TO01000107"],"award-info":[{"award-number":["TO01000107"]}],"id":[{"id":"https:\/\/ror.org\/04v0fk911","id-type":"ROR","asserted-by":"crossref"}]},{"name":"IAPG institutional","award":["RVO 67985904"],"award-info":[{"award-number":["RVO 67985904"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Retinal pigment epithelium (RPE) is a critical cell monolayer forming the blood-retina-barrier (BRB) and a permeable bridge between the choriocapillaris and the retina. RPE is also crucial in maintaining photoreceptor function and for completing the visual cycle. Loss of the RPE is associated with the development of degenerative diseases like age-related macular degeneration (AMD). To treat diseases like AMD, pluripotent stem cell-derived RPE (pRPE) has been recently explored extensively as a regenerative module. pRPE like other ectodermal tissues requires specific lineage differentiation and long-term in vitro culturing for maturation. Therefore, understanding the differentiation process of RPE could be useful for stem cell-based RPE derivation. Developing pRPE-based transplants and delivering them into the subretinal space is another aspect that has garnered interest in the last decade. In this review, we discuss the basic strategies currently employed for stem cell-based RPE derivation, their delivery, and recent clinical studies related to pRPE transplantation in patients. We have also discussed a few limitations with in vitro RPE culture and potential solutions to overcome such problems which can be helpful in developing functional RPE tissue.<\/jats:p>","DOI":"10.1093\/stcltm\/szad039","type":"journal-article","created":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T18:36:14Z","timestamp":1687286174000},"page":"536-552","source":"Crossref","is-referenced-by-count":33,"title":["Progress in Stem Cells-Based Replacement Therapy for Retinal Pigment Epithelium: In Vitro Differentiation to In Vivo Delivery"],"prefix":"10.1093","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1733-7382","authenticated-orcid":false,"given":"Santosh","family":"Gupta","sequence":"first","affiliation":[{"name":"Center for Eye Research and Innovative Diagnostics, Department of Ophthalmology, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo , Oslo , Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyubomyr","family":"Lytvynchuk","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Justus Liebig University Giessen, University Hospital Giessen and Marburg GmbH , Giessen , Germany"},{"name":"Department of Ophthalmology, Karl Landsteiner Institute for Retinal Research and Imaging , Vienna , Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taras","family":"Ardan","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Regeneration and Cell Plasticity, Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic , Libechov , Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana","family":"Studenovska","sequence":"additional","affiliation":[{"name":"Department of Biomaterials and Bioanalogous Systems, Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic , Prague , Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruchi","family":"Sharma","sequence":"additional","affiliation":[{"name":"Ocular and Stem Cell Translational Research, National Eye Institute, National Institutes of Health , Bethesda, MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgina","family":"Faura","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Institute of Clinical Medicine, University of Oslo , Oslo , Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Eide","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Institute of Clinical Medicine, University of Oslo , Oslo , Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rama","family":"Shanker Verma","sequence":"additional","affiliation":[{"name":"Stem Cell and Molecular Biology, Laboratory, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences. Indian Institute of Technology Madras , Chennai, Tamil Nadu , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ljubo","family":"Znaor","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Split School of Medicine and University Hospital Centre , Split , Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3208-7705","authenticated-orcid":false,"given":"Slaven","family":"Erceg","sequence":"additional","affiliation":[{"name":"Research Center \u201cPrincipe Felipe,\u201d Stem Cell Therapies in Neurodegenerative Diseases Laboratory , Valencia , Spain"},{"name":"Department of Neuroregeneration, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic , Prague , Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Knut","family":"Stieger","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Justus Liebig University Giessen, University Hospital Giessen and Marburg GmbH , Giessen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Motlik","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Regeneration and Cell Plasticity, Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic , Libechov , Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goran","family":"Petrovski","sequence":"additional","affiliation":[{"name":"Center for Eye Research and Innovative Diagnostics, Department of Ophthalmology, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo , Oslo , Norway"},{"name":"Department of Ophthalmology, University of Split School of Medicine and University Hospital Centre , Split , Croatia"},{"name":"Department of Ophthalmology, Oslo University Hospital , Oslo , Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kapil","family":"Bharti","sequence":"additional","affiliation":[{"name":"Ocular and Stem Cell Translational Research, National Eye Institute, National Institutes of Health , Bethesda, MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,7,17]]},"reference":[{"issue":"24","key":"2023081609091603000_CIT0001","doi-asserted-by":"crossref","first-page":"2606","DOI":"10.1056\/NEJMra0801537","article-title":"Age-related macular degeneration","volume":"358","author":"Jager","year":"2008","journal-title":"N Engl J Med"},{"issue":"2","key":"2023081609091603000_CIT0002","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1111\/opo.12675","article-title":"Risk factors for progression of age-related macular degeneration","volume":"40","author":"Heesterbeek","year":"2020","journal-title":"Ophthalmic Physiol 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