{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T02:09:50Z","timestamp":1790388590710,"version":"4.1.0"},"reference-count":24,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T00:00:00Z","timestamp":1715558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Pfizer"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>(1) Background: We reviewed a stem cell-derived therapeutic strategy for advanced neovascular age-related macular degeneration (nAMD) using a human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE) monolayer delivered on a coated, synthetic basement membrane (BM)\u2014the patch\u2014and assessed the presence and distribution of hESC-RPE over 5 years following transplantation, as well as functional outcomes. (2) Methods: Two subjects with acute vision loss due to sub-macular haemorrhage in advanced nAMD received the hESC-RPE patch. Systematic immunosuppression was used peri-operatively followed by local depot immunosuppression. The subjects were monitored for five years with observation of RPE patch pigmentation, extension beyond the patch boundary into surrounding retina, thickness of hESC-RPE and synthetic BM and review for migration and proliferation of hESC-RPE. Visual function was also assessed. (3) Results: The two study participants showed clear RPE characteristics of the patch, preservation of some retinal ultrastructure with signs of remodelling, fibrosis and thinning on optical coherence tomography over the 5-year period. For both participants, there was evidence of pigment extension beyond the patch continuing until 12 months post-operatively, which stabilised and was preserved until 5 years post-operatively. Measurement of hESC-RPE and BM thickness over time for both cases were consistent with predefined histological measurements of these two layers. There was no evidence of distant RPE migration or proliferation in either case beyond the monolayer. Sustained visual acuity improvement was apparent for 2 years in both subjects, with one subject maintaining the improvement for 5 years. Both subjects demonstrated initial improvement in fixation and microperimetry compared to baseline, at year 1, although only one maintained this at 4 years post-intervention. (4) Conclusions: hESC-RPE patches show evidence of continued pigmentation, with extension, to cover bare host basement membrane for up to 5 years post-implantation. There is evidence that this represents functional RPE on the patch and at the patch border where host RPE is absent. The measurements for thickness of hESC-RPE and BM suggest persistence of both layers at 5 years. No safety concerns were raised for the hypothetical risk of RPE migration, proliferation or tumour formation. Visual function also showed sustained improvement for 2 years in one subject and 5 years in the other subject.<\/jats:p>","DOI":"10.3390\/diagnostics14101005","type":"journal-article","created":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T08:33:03Z","timestamp":1715589183000},"page":"1005","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The Fate of RPE Cells Following hESC-RPE Patch Transplantation in Haemorrhagic Wet AMD: Pigmentation, Extension of Pigmentation, Thickness of Transplant, Assessment for Proliferation and Visual Function\u2014A 5 Year-Follow Up"],"prefix":"10.3390","volume":"14","author":[{"given":"Lyndon","family":"da Cruz","sequence":"first","affiliation":[{"name":"The London Project to Cure Blindness, ORBIT, Institute of Ophthalmology, University College London (UCL), London WC1E 6BT, UK"},{"name":"National Institute of Health and Care Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust, Institute of Ophthalmology, University College London (UCL), London WC1E 6BT, UK"},{"name":"Moorfields Eye Hospital NHS Foundation Trust, 162 City Road, London EC1V 2PD, UK"},{"name":"Wellcome\/EPSRC Centre for Interventional & Surgical Sciences (WEISS), Charles Bell House, London W1W 7TY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2756-3674","authenticated-orcid":false,"given":"Taha","family":"Soomro","sequence":"additional","affiliation":[{"name":"The London Project to Cure Blindness, ORBIT, Institute of Ophthalmology, University College London (UCL), London WC1E 6BT, UK"},{"name":"National Institute of Health and Care Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust, Institute of Ophthalmology, University College London (UCL), London WC1E 6BT, UK"},{"name":"Moorfields Eye Hospital NHS Foundation Trust, 162 City Road, London EC1V 2PD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odysseas","family":"Georgiadis","sequence":"additional","affiliation":[{"name":"The London Project to Cure Blindness, ORBIT, Institute of Ophthalmology, University College London (UCL), London WC1E 6BT, UK"},{"name":"National Institute of Health and Care Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust, Institute of Ophthalmology, University College London (UCL), London WC1E 6BT, UK"},{"name":"Moorfields Eye Hospital NHS Foundation Trust, 162 City Road, London EC1V 2PD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britta","family":"Nommiste","sequence":"additional","affiliation":[{"name":"The London Project to Cure Blindness, ORBIT, Institute of Ophthalmology, University College London (UCL), London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1530-3824","authenticated-orcid":false,"given":"Mandeep S.","family":"Sagoo","sequence":"additional","affiliation":[{"name":"National Institute of Health and Care Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust, Institute of Ophthalmology, University College London (UCL), London WC1E 6BT, UK"},{"name":"Moorfields Eye Hospital NHS Foundation Trust, 162 City Road, London EC1V 2PD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5427-2939","authenticated-orcid":false,"given":"Peter","family":"Coffey","sequence":"additional","affiliation":[{"name":"The London Project to Cure Blindness, ORBIT, Institute of Ophthalmology, University College London (UCL), London WC1E 6BT, UK"},{"name":"National Institute of Health and Care Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust, Institute of Ophthalmology, University College London (UCL), London WC1E 6BT, UK"},{"name":"Center for Stem Cell Biology and Engineering, Neuroscience Research Institute, University of California, Santa Barbara, CA 93106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","article-title":"Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors","volume":"126","author":"Takahashi","year":"2006","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"ORSFc1","DOI":"10.1167\/iovs.15-18681","article-title":"Subretinal transplantation of embryonic stem cell\u2013derived retinal pigment epithelium for the treatment of macular degeneration: An assessment at 4 years","volume":"57","author":"Schwartz","year":"2016","journal-title":"Investig. 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