{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T15:03:06Z","timestamp":1790348586714,"version":"4.1.0"},"reference-count":134,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biotechnology Journal"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Retinal degenerative diseases, including age\u2010related macular degeneration, retinitis pigmentosa, diabetic retinopathy, and inherited retinal dystrophies, are among the leading causes of irreversible vision loss and blindness worldwide. Current treatments primarily slow disease progression and are unable to restore lost retinal cells or visual function, highlighting the need for regenerative therapeutic strategies. Stem cell\u2010based therapies have emerged as a promising approach for retinal repair through multiple mechanisms, including retinal cell replacement, stimulation of endogenous regeneration, cellular reprogramming, immunomodulation, and paracrine signaling. This narrative review provides a comprehensive overview of the major stem cell sources investigated for retinal regeneration. In addition, the roles of extracellular vesicles and retinal organoids as emerging therapeutic platforms are discussed. Particular emphasis is placed on comparing the biological rationale, therapeutic potential, current preclinical and clinical evidence, and translational readiness of each approach. Despite encouraging progress, several challenges continue to limit routine clinical application, including poor survival and integration of transplanted cells, immune rejection, tumorigenicity, genomic instability, variability in differentiation efficiency, manufacturing standardization, and long\u2010term safety. Continued advances in stem cell biology, tissue engineering, gene editing, and clinical trial design are expected to accelerate the development of safe and effective regenerative therapies for retinal diseases.<\/jats:p>","DOI":"10.1002\/biot.70311","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T10:57:38Z","timestamp":1790333858000},"source":"Crossref","is-referenced-by-count":0,"title":["Stem Cell\u2010Based Strategies for Retinal Cell Restoration"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7364-1201","authenticated-orcid":false,"given":"Behzad","family":"Safarpour Lima","sequence":"first","affiliation":[{"name":"Miramichi EyeNB Centre of Excellence  Miramichi New Brunswick Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0013-7245","authenticated-orcid":false,"given":"Shima","family":"Sayanjali","sequence":"additional","affiliation":[{"name":"Miramichi EyeNB Centre of Excellence  Miramichi New Brunswick Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6386-2116","authenticated-orcid":false,"given":"Nir","family":"Shoham\u2010Hazon","sequence":"additional","affiliation":[{"name":"Miramichi EyeNB Centre of Excellence  Miramichi New Brunswick Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12015\u2010024\u201010740\u20104"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.4252\/wjsc.v11.i11.957"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.4252\/wjsc.v13.i10.1446"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2022.03.001"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics16101299"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.16\u201019127"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2018.05.005"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvb.2020.103377"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.glmedi.2023.100046"},{"issue":"3","key":"e_1_2_14_11_1","first-page":"425","article-title":"Role of Wnt Signaling Pathway in Stem Cells Derived Retinal Regeneration","volume":"41","author":"Yang K.","year":"2019","journal-title":"Acta Academiae Medicinae Sinicae"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aopr.2024.02.001"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12015\u2010017\u20109750\u20104"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2021.12.008"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951\u2010025\u201003095\u20106"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010026\u201002582\u2010y"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.70127"},{"key":"e_1_2_14_18_1","first-page":"1701","article-title":"The Expression of Retinal Cell Markers in Human Retinal Pigment Epithelial Cells and Their Augmentation by the Synthetic Retinoid Fenretinide","volume":"17","author":"Carr A. J.","year":"2011","journal-title":"Molecular Vision"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/stmcls\/sxag023"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.3365"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109022"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reth.2024.05.018"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2018.11.003"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.48130\/vns\u20100025\u20100012"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reth.2022.12.005"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reth.2024.06.013"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.slast.2023.10.004"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.slast.2023.07.004"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep29784"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2022.09.014"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2024.06.009"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2024.09.002"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/APO.0000000000000520"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00334"},{"key":"e_1_2_14_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2023.11.004"},{"key":"e_1_2_14_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.irn.2022.09.004"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/life14060668"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.3791\/65848"},{"key":"e_1_2_14_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2022.120570"},{"key":"e_1_2_14_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20102542"},{"key":"e_1_2_14_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2025.151411"},{"key":"e_1_2_14_42_1","doi-asserted-by":"publisher","DOI":"10.2174\/1567202616666190618123931"},{"key":"e_1_2_14_43_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389450120666191121103831"},{"key":"e_1_2_14_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.630645"},{"key":"e_1_2_14_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287\u2010025\u201004826\u20100"},{"key":"e_1_2_14_46_1","doi-asserted-by":"publisher","DOI":"10.18103\/mra.v11i11.4784"},{"key":"e_1_2_14_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.70188"},{"key":"e_1_2_14_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/ceo.14309"},{"key":"e_1_2_14_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cdev.2023.203848"},{"key":"e_1_2_14_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40135\u2010019\u201000195\u2010z"},{"key":"e_1_2_14_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reth.2024.09.001"},{"key":"e_1_2_14_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432\u2010022\u201004206\u20108"},{"key":"e_1_2_14_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2021.02.006"},{"key":"e_1_2_14_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-14-130"},{"key":"e_1_2_14_55_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.46332"},{"key":"e_1_2_14_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13905"},{"key":"e_1_2_14_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287\u2010022\u201002894\u20100"},{"key":"e_1_2_14_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2023.12.001"},{"key":"e_1_2_14_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.pbr.2020.05.026"},{"key":"e_1_2_14_60_1","article-title":"Cellular Signaling in M\u00fcller glia: Progenitor Cells for Regenerative and Neuroprotective Responses in Pharmacological Models of Retinal Degeneration","volume":"4","author":"Liu Y.","year":"2019","journal-title":"Journal of Ophthalmology"},{"key":"e_1_2_14_61_1","doi-asserted-by":"publisher","DOI":"10.1089\/jop.2020.0088"},{"key":"e_1_2_14_62_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2017.0111"},{"key":"e_1_2_14_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2021.108569"},{"key":"e_1_2_14_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41374\u2010020\u20100470\u2010z"},{"key":"e_1_2_14_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2021.06.002"},{"key":"e_1_2_14_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.survophthal.2023.09.003"},{"key":"e_1_2_14_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-443-15583-3.00044-5"},{"key":"e_1_2_14_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2021.100970"},{"key":"e_1_2_14_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/ceo.14128"},{"key":"e_1_2_14_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2014.10.002"},{"key":"e_1_2_14_71_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640\u2010022\u201000564\u2010w"},{"key":"e_1_2_14_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41536-025-00407-0"},{"key":"e_1_2_14_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2024.12.005"},{"key":"e_1_2_14_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2025.114196"},{"key":"e_1_2_14_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reth.2025.11.002"},{"key":"e_1_2_14_76_1","doi-asserted-by":"publisher","DOI":"10.48130\/vns\u20100025\u20100003"},{"key":"e_1_2_14_77_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010025\u201004059\u20107"},{"key":"e_1_2_14_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003\u2010023\u201004543\u20105"},{"key":"e_1_2_14_79_1","doi-asserted-by":"publisher","DOI":"10.48130\/vns\u20100025\u20100013"},{"key":"e_1_2_14_80_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010023\u201001873\u20100"},{"key":"e_1_2_14_81_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26073263"},{"key":"e_1_2_14_82_1","doi-asserted-by":"publisher","DOI":"10.1007\/s44443\u2010025\u201000085\u20104"},{"key":"e_1_2_14_83_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12015\u2010023\u201010661\u20108"},{"key":"e_1_2_14_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2026.102898"},{"key":"e_1_2_14_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2024.102277"},{"key":"e_1_2_14_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2025.101356"},{"key":"e_1_2_14_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2019.100824"},{"key":"e_1_2_14_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.pmbts.2023.03.026"},{"key":"e_1_2_14_89_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673\u20105374.219028"},{"key":"e_1_2_14_90_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.286947"},{"key":"e_1_2_14_91_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13597"},{"key":"e_1_2_14_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2019.11.002"},{"key":"e_1_2_14_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2022.07.064"},{"key":"e_1_2_14_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2021.03.012"},{"key":"e_1_2_14_95_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20103\u2010319\u201017121\u20100_74"},{"key":"e_1_2_14_96_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.05.186"},{"key":"e_1_2_14_97_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.102618"},{"key":"e_1_2_14_98_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2022.108961"},{"key":"e_1_2_14_99_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.70100"},{"key":"e_1_2_14_100_1","first-page":"171","volume-title":"The Eye","author":"Zhang H.","year":"2023"},{"key":"e_1_2_14_101_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.813538"},{"key":"e_1_2_14_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiosc.2022.02.002"},{"key":"e_1_2_14_103_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-323-90120-8.00016-2"},{"key":"e_1_2_14_104_1","first-page":"1","article-title":"AI Framework for Multidisease Detection via Retinal Imaging","volume":"7","author":"Zhang X.","year":"2026","journal-title":"Nature Medicine"},{"key":"e_1_2_14_105_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4114"},{"key":"e_1_2_14_106_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics14101005"},{"key":"e_1_2_14_107_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1608368"},{"key":"e_1_2_14_108_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10112951"},{"key":"e_1_2_14_109_1","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.2016.1093110"},{"key":"e_1_2_14_110_1","doi-asserted-by":"publisher","DOI":"10.1177\/09636897251400835"},{"key":"e_1_2_14_111_1","doi-asserted-by":"publisher","DOI":"10.21037\/sci.2018.04.02"},{"key":"e_1_2_14_112_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellin.2024.100223"},{"key":"e_1_2_14_113_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287\u2010025\u201004771\u2010y"},{"key":"e_1_2_14_114_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(14)61376\u20103"},{"key":"e_1_2_14_115_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2015.04.005"},{"key":"e_1_2_14_116_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.17\u201022855"},{"key":"e_1_2_14_117_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13619\u2010021\u201000097\u20101"},{"key":"e_1_2_14_118_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12015\u2010024\u201010802\u20107"},{"key":"e_1_2_14_119_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2018.09.001"},{"key":"e_1_2_14_120_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.22800"},{"key":"e_1_2_14_121_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2021.108630"},{"key":"e_1_2_14_122_1","first-page":"193","volume-title":"The Eye","author":"Taher E. E.","year":"2023"},{"key":"e_1_2_14_123_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-05222-5_2"},{"key":"e_1_2_14_124_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cobme.2024.100538"},{"key":"e_1_2_14_125_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diff.2023.04.002"},{"key":"e_1_2_14_126_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2021.03.036"},{"key":"e_1_2_14_127_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.300329"},{"key":"e_1_2_14_128_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgr.2024.12.008"},{"key":"e_1_2_14_129_1","doi-asserted-by":"publisher","DOI":"10.15283\/ijsc19127"},{"key":"e_1_2_14_130_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.62.9.30"},{"key":"e_1_2_14_131_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.70264"},{"key":"e_1_2_14_132_1","doi-asserted-by":"publisher","DOI":"10.1134\/S0006297919030052"},{"key":"e_1_2_14_133_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2013.0049"},{"key":"e_1_2_14_134_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10061426"},{"key":"e_1_2_14_135_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2025.102543"}],"container-title":["Biotechnology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/biot.70311","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/biot.70311","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/biot.70311","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T14:33:12Z","timestamp":1790346792000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/biot.70311"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":134,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/biot.70311"],"URL":"https:\/\/doi.org\/10.1002\/biot.70311","archive":["Portico"],"relation":{},"ISSN":["1860-6768","1860-7314"],"issn-type":[{"value":"1860-6768","type":"print"},{"value":"1860-7314","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"article-number":"e70311"}}