{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T02:22:19Z","timestamp":1762050139198,"version":"build-2065373602"},"reference-count":115,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T00:00:00Z","timestamp":1652054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Inherited retinal dystrophies and retinal degenerations related to more common diseases (i.e., age-related macular dystrophy) are a major issue and one of the main causes of low vision in pediatric and elderly age groups. Advancement and understanding in molecular biology and the possibilities raised by gene-editing techniques opened a new era for clinicians and patients due to feasible possibilities of treating disabling diseases and the reduction in their complications burden. The scope of this review is to focus on the state-of-the-art in somatic cell therapy medicinal products as the basis of new insights and possibilities to use this approach to treat rare eye diseases.<\/jats:p>","DOI":"10.3390\/life12050708","type":"journal-article","created":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T00:30:28Z","timestamp":1652142628000},"page":"708","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Treatment of Inherited Retinal Dystrophies with Somatic Cell Therapy Medicinal Product: A Review"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8741-4833","authenticated-orcid":false,"given":"Giacomo Maria","family":"Bacci","sequence":"first","affiliation":[{"name":"Pediatric Ophthalmology Unit, Children\u2019s Hospital A. Meyer-University of Florence, 50139 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2711-0088","authenticated-orcid":false,"given":"Valentina","family":"Becherucci","sequence":"additional","affiliation":[{"name":"Cell Factory Meyer, Children\u2019s Hospital A. Meyer-University of Florence, 50139 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6676-9379","authenticated-orcid":false,"given":"Elisa","family":"Marziali","sequence":"additional","affiliation":[{"name":"Pediatric Ophthalmology Unit, Children\u2019s Hospital A. Meyer-University of Florence, 50139 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Sodi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, 50139 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1945-8324","authenticated-orcid":false,"given":"Franco","family":"Bambi","sequence":"additional","affiliation":[{"name":"Cell Factory Meyer, Children\u2019s Hospital A. Meyer-University of Florence, 50139 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Caputo","sequence":"additional","affiliation":[{"name":"Pediatric Ophthalmology Unit, Children\u2019s Hospital A. Meyer-University of Florence, 50139 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1146\/annurev-vision-082114-035334","article-title":"Functional Circuitry of the Retina","volume":"1","author":"Demb","year":"2015","journal-title":"Annu. Rev. Vis. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1038\/nn0901-877","article-title":"The fundamental plan of the retina","volume":"4","author":"Masland","year":"2001","journal-title":"Nat. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.neuron.2012.10.002","article-title":"The Neuronal Organization of the Retina","volume":"76","author":"Masland","year":"2012","journal-title":"Neuron"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.ceb.2019.08.001","article-title":"Retinal pigment epithelium polarity in health and blinding diseases","volume":"62","author":"Caceres","year":"2019","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.survophthal.2006.02.007","article-title":"Progressive Cone and Cone-Rod Dystrophies: Phenotypes and Underlying Molecular Genetic Basis","volume":"51","author":"Michaelides","year":"2006","journal-title":"Surv. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1080\/08164622.2021.1880863","article-title":"Gene therapy for inherited retinal diseases: Progress and possibilities","volume":"104","author":"Hu","year":"2021","journal-title":"Clin. Exp. Optom."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"205","DOI":"10.4103\/tjo.tjo_32_21","article-title":"Management and treatment of inherited retinal dystrophies","volume":"11","author":"Levi","year":"2021","journal-title":"Taiwan J. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1136\/jmg.40.9.641","article-title":"The genetics of inherited macular dystrophies","volume":"40","author":"Michaelides","year":"2003","journal-title":"J. Med. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1086\/302251","article-title":"Genotype\/Phenotype Analysis of a Photoreceptor-Specific ATP-Binding Cassette Transporter Gene, ABCR, in Stargardt Disease","volume":"64","author":"Lewis","year":"1999","journal-title":"Am. J. Hum. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.ophtha.2014.08.032","article-title":"Early-Onset Stargardt Disease","volume":"122","author":"Lambertus","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1097\/IIO.0000000000000375","article-title":"Stargardt Disease: Gene Therapy Strategies for ABCA4","volume":"61","author":"Ku","year":"2021","journal-title":"Int. Ophthalmol. Clin."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.preteyeres.2018.03.005","article-title":"Non-syndromic retinitis pigmentosa","volume":"66","author":"Verbakel","year":"2018","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/1750-1172-1-40","article-title":"Retinitis pigmentosa","volume":"1","author":"Hamel","year":"2006","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_14","unstructured":"Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Gripp, K.W., Mirzaa, G.M., and Amemiya, A. (1993). Nonsyndromic Retinitis Pigmentosa Overview, University of Washington."},{"key":"ref_15","unstructured":"(2022, April 21). Regulation (EC) No. 1394\/2007 of the European Parliament and of the Council of 13 November 2007 on Advanced Therapy Medicinal Products and Amending Directive 2001\/83\/EC and Regulation \/EC N0 726\/2004. Available online: https:\/\/eur-lex.europa.eu\/LexUriServ\/LexUriServ.do?uri=OJ:L:2007:324:0121:0137:en:PDF."},{"key":"ref_16","unstructured":"(2022, April 21). Regulation (EU) No. 536\/2014 of the European Parliament and of the Council of 16 April 2014 on Clinical Trials on Medicinal Products for Human Use, and Repealing Directive 2001\/20\/EC. Available online: https:\/\/ec.europa.eu\/health\/system\/files\/2016-11\/reg_2014_536_en_0.pdf."},{"key":"ref_17","unstructured":"(2022, April 21). Commission Directive 2005\/28\/EC of 8 April 2005 Laying down Principles and Detailed Guidelines for Good Clinical Practice as Regards Investigational Medicinal Products for Human Use. Available online: https:\/\/eur-lex.europa.eu\/legal-content\/EN\/TXT\/PDF\/?uri=CELEX:32005L0028&from=CS."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.exer.2018.07.019","article-title":"The current state of stem cell therapy for ocular disease","volume":"177","author":"Bobba","year":"2018","journal-title":"Exp. Eye Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Paniagua, M., de la Mata, A., Galindo, S., Bl\u00e1zquez, F., Calonge, M., and Nieto-Miguel, T. (2021). Advanced Therapy Medicinal Products for the Eye: Definitions and Regulatory Framework. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13030347"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"299","DOI":"10.2147\/BTT.S290331","article-title":"Stem Cell Therapy for Retinal Degeneration: The Evidence to Date","volume":"15","author":"Sharma","year":"2021","journal-title":"Biol. Targets Ther."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Garg, A., Yang, J., Lee, W., and Tsang, S.H. (2017). Stem Cell Therapies in Retinal Disorders. Cells, 6.","DOI":"10.3390\/cells6010004"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/ar.22800","article-title":"Retinal Stem Cells and Regeneration of Vision System","volume":"297","author":"Yip","year":"2013","journal-title":"Anat. Rec."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1038\/s41419-020-02955-3","article-title":"Stem\/progenitor cell-based transplantation for retinal degeneration: A review of clinical trials","volume":"11","author":"Wang","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1634\/stemcells.2005-0311","article-title":"High Yield of Cells Committed to the Photoreceptor Fate from Expanded Mouse Retinal Stem Cells","volume":"24","author":"Canola","year":"2006","journal-title":"Stem Cells"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/nature05161","article-title":"Retinal repair by transplantation of photoreceptor precursors","volume":"444","author":"MacLaren","year":"2006","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.exer.2009.03.025","article-title":"Growth kinetics and transplantation of human retinal progenitor cells","volume":"89","author":"Aftab","year":"2009","journal-title":"Exp. Eye Res."},{"key":"ref_27","first-page":"1759","article-title":"Combining chondroitinase ABC and growth factors promotes the integration of murine retinal progenitor cells transplanted into Rho\u2212\/\u2212 mice","volume":"17","author":"Ma","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nature10997","article-title":"Restoration of vision after transplantation of photoreceptors","volume":"485","author":"Pearson","year":"2012","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1073\/pnas.1212677110","article-title":"Repair of the degenerate retina by photoreceptor transplantation","volume":"110","author":"Barber","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1055\/s-2005-836488","article-title":"Ethical aspects of use of fetal\/embryonic cells in treatment and research","volume":"66","author":"Watt","year":"2005","journal-title":"Zent. Neurochir."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/74447","article-title":"Embryonic stem cell lines from human blastocysts: Somatic differentiation in vitro","volume":"18","author":"Reubinoff","year":"2000","journal-title":"Nat. Biotechnol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1056\/NEJMsr040330","article-title":"Derivation of Embryonic Stem-Cell Lines from Human Blastocysts","volume":"350","author":"Cowan","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1002\/neu.10031","article-title":"Neural cell differentiation from retinal pigment epithelial cells of the newt: An organ culture model for the urodele retinal regeneration","volume":"50","author":"Ikegami","year":"2002","journal-title":"J. Neurobiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1038\/nprot.2009.51","article-title":"Stepwise differentiation of pluripotent stem cells into retinal cells","volume":"4","author":"Osakada","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_35","first-page":"558","article-title":"Toward the defined and xeno-free differentiation of functional human pluripotent stem cell-derived retinal pigment epithelial cells","volume":"17","author":"Vaajasaari","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"216","DOI":"10.5653\/cerm.2011.38.4.216","article-title":"Subretinal transplantation of putative retinal pigment epithelial cells derived from human embryonic stem cells in rat retinal degeneration model","volume":"38","author":"Park","year":"2011","journal-title":"Clin. Exp. Reprod. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s12041-009-0063-5","article-title":"Induced pluripotent stem cells for retinal degenerative diseases: A new perspective on the challenges","volume":"88","author":"Jin","year":"2009","journal-title":"J. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/S0140-6736(12)60028-2","article-title":"Embryonic stem cell trials for macular degeneration: A preliminary report","volume":"379","author":"Schwartz","year":"2012","journal-title":"Lancet"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1002\/dvdy.10425","article-title":"Generation of structures formed by lens and retinal cells differentiating from embryonic stem cells","volume":"228","author":"Hirano","year":"2003","journal-title":"Dev. Dyn."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/s00417-007-0710-6","article-title":"Transplantation of cells from eye-like structures differentiated from embryonic stem cells in vitro and in vivo regeneration of retinal ganglion-like cells","volume":"246","author":"Aoki","year":"2007","journal-title":"Graefes. Arch. Clin. Exp. Ophthalmol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/j.conb.2012.02.005","article-title":"Self-formation of layered neural structures in three-dimensional culture of ES cells","volume":"22","author":"Eiraku","year":"2012","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1089\/ten.tea.2007.0358","article-title":"Engineering Retina from Human Retinal Progenitors (Cell Lines)","volume":"15","author":"Dutt","year":"2009","journal-title":"Tissue Eng. Part A"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.jneumeth.2010.04.025","article-title":"Three-dimensional early retinal progenitor 3D tissue constructs derived from human embryonic stem cells","volume":"190","author":"Nistor","year":"2010","journal-title":"J. Neurosci. Methods"},{"key":"ref_44","first-page":"3843","article-title":"Stem cell-based therapies for age-related macular degeneration: Current status and prospects","volume":"7","author":"Mu","year":"2014","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"ORSFc1","DOI":"10.1167\/iovs.15-18681","article-title":"Subretinal transplantation of embryonic stem cell-derived retinal pigment epithelium for the treatment of macular degeneration: An assessment at 4 years","volume":"57","author":"Schwartz","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/S0140-6736(14)61376-3","article-title":"Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt\u2019s macular dystrophy: Follow-up of two open-label phase 1\/2 studies","volume":"385","author":"Schwartz","year":"2015","journal-title":"Lancet"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4251","DOI":"10.1167\/iovs.03-1108","article-title":"Neurally Selected Embryonic Stem Cells Induce Tumor Formation after Long-Term Survival following Engraftment into the Subretinal Space","volume":"45","author":"Arnhold","year":"2004","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.3390\/jcm3041511","article-title":"iPS Cells for Modelling and Treatment of Retinal Diseases","volume":"3","author":"Chen","year":"2014","journal-title":"J. Clin. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1126\/science.1154884","article-title":"Generation of pluripotent stem cells from adult mouse liver and stomach cells","volume":"321","author":"Aoi","year":"2008","journal-title":"Science"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors","volume":"131","author":"Takahashi","year":"2007","journal-title":"Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3081","DOI":"10.1038\/nprot.2007.418","article-title":"Induction of pluripotent stem cells from fibroblast cultures","volume":"2","author":"Takahashi","year":"2007","journal-title":"Nat. Protoc."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1002\/stem.189","article-title":"Derivation of Functional Retinal Pigmented Epithelium from Induced Pluripotent Stem Cells","volume":"27","author":"Buchholz","year":"2009","journal-title":"Stem Cells"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1002\/stem.635","article-title":"Human induced pluripotent stem-derived retinal pigment epithelium (RPE) cells exhibit ion transport, membrane potential, polarized vascular endothelial growth factor secretion, and gene expression pattern similar to native RPE","volume":"29","author":"Kokkinaki","year":"2011","journal-title":"Stem Cells"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.2119\/molmed.2012.00242","article-title":"Long-term Safety and Efficacy of Human-Induced Pluripotent Stem Cell (iPS) Grafts in a Preclinical Model of Retinitis Pigmentosa","volume":"18","author":"Li","year":"2012","journal-title":"Mol. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"34484","DOI":"10.1074\/jbc.M113.518571","article-title":"Retinal Pigmented Epithelial Cells Obtained from Human Induced Pluripotent Stem Cells Possess Functional Visual Cycle Enzymes In Vitro and In Vivo","volume":"288","author":"Maeda","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Tucker, B.A., Park, I.-H., Qi, S.D., Klassen, H.J., Jiang, C., Yao, J., Redenti, S., Daley, G.Q., and Young, M.J. (2011). Transplantation of Adult Mouse iPS Cell-Derived Photoreceptor Precursors Restores Retinal Structure and Function in Degenerative Mice. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0018992"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"25","DOI":"10.3109\/08820538.2015.1115253","article-title":"Stem Cell-Based Therapy for Diseases of the Retinal Pigment Epithelium: From Bench to Bedside","volume":"31","author":"Sachdeva","year":"2016","journal-title":"Semin. Ophthalmol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Lamba, D.A., McUsic, A., Hirata, R.K., Wang, P.-R., Russell, D., and Reh, T.A. (2010). Generation, Purification and Transplantation of Photoreceptors Derived from Human Induced Pluripotent Stem Cells. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0008763"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"8785","DOI":"10.1167\/iovs.11-8129","article-title":"Induction of Retinal Pigment Epithelial Cells from Monkey iPS Cells","volume":"52","author":"Okamoto","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.preteyeres.2019.03.001","article-title":"Photoreceptor cell replacement in macular degeneration and retinitis pigmentosa: A pluripotent stem cell-based approach","volume":"71","author":"Gagliardi","year":"2019","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"ORSFd1","DOI":"10.1167\/iovs.16-19127","article-title":"Stem Cell Sources and Their Potential for the Treatment of Retinal Degenerations","volume":"57","author":"Vergara","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1002\/stem.2852","article-title":"Concise Review: Current Status of Three-Dimensional Organoids as Preclinical Models","volume":"36","author":"Kaushik","year":"2018","journal-title":"Stem Cells"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.ydbio.2017.09.028","article-title":"Organoid technology for retinal repair","volume":"433","author":"Llonch","year":"2018","journal-title":"Dev. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4047","DOI":"10.1038\/ncomms5047","article-title":"Generation of three-dimensional retinal tissue with functional photoreceptors from human iPSCs","volume":"5","author":"Zhong","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1038\/s41598-017-00774-9","article-title":"Photoreceptor Outer Segment-like Structures in Long-Term 3D Retinas from Human Pluripotent Stem Cells","volume":"7","author":"Wahlin","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Xu, Z., Yuan, F., Jin, K., and Xiang, M. (2021). Retinal Organoid Technology: Where Are We Now?. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910244"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"100779","DOI":"10.1016\/j.preteyeres.2019.100779","article-title":"Retinal stem cell transplantation: Balancing safety and potential","volume":"75","author":"Singh","year":"2019","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"8518","DOI":"10.1073\/pnas.1324212111","article-title":"From confluent human iPS cells to self-forming neural retina and retinal pigmented epithelium","volume":"111","author":"Reichman","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1002\/stem.2586","article-title":"Generation of Storable Retinal Organoids and Retinal Pigmented Epithelium from Adherent Human iPS Cells in Xeno-Free and Feeder-Free Conditions","volume":"35","author":"Reichman","year":"2017","journal-title":"Stem Cells"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"632","DOI":"10.4252\/wjsc.v13.i6.632","article-title":"Potential therapeutic applications of mesenchymal stem cells for the treatment of eye diseases","volume":"13","author":"Mannino","year":"2021","journal-title":"World J. Stem Cells"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"6286","DOI":"10.1038\/ncomms7286","article-title":"Generation of a ciliary margin-like stem cell niche from self-organizing human retinal tissue","volume":"6","author":"Kuwahara","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Ding, S.S.L., Subbiah, S.K., Khan, M.S.A., Farhana, A., and Mok, P.L. (2019). Empowering Mesenchymal Stem Cells for Ocular Degenerative Disorders. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20071784"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Holan, V., Palacka, K., and Hermankova, B. (2021). Mesenchymal Stem Cell-Based Therapy for Retinal Degenerative Diseases: Experimental Models and Clinical Trials. Cells, 10.","DOI":"10.3390\/cells10030588"},{"key":"ref_74","first-page":"17","article-title":"Cellular mechanisms of emerging applications of mesenchymal stem cells","volume":"35","author":"Mok","year":"2013","journal-title":"Malays. J. Pathol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/14653240600855905","article-title":"Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement","volume":"8","author":"Dominici","year":"2006","journal-title":"Cytotherapy"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1080\/14653240500319234","article-title":"Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement","volume":"7","author":"Horwitz","year":"2005","journal-title":"Cytotherapy"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3727\/096368910X","article-title":"Mesenchymal Stem Cells","volume":"20","author":"Ding","year":"2011","journal-title":"Cell Transplant."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jocit.2014.12.001","article-title":"Mesenchymal stem cells: Immunomodulatory capability and clinical potential in immune diseases","volume":"2","author":"Zhao","year":"2016","journal-title":"J. Cell Immunother."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1007\/s12015-020-10090-x","article-title":"A Review on Mesenchymal Stem Cells for Treatment of Retinal Diseases","volume":"17","author":"Adak","year":"2021","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"321","DOI":"10.2217\/rme-2019-0022","article-title":"The use of mesenchymal stem cells for the treatment of progressive retinal diseases: A review","volume":"14","author":"Boruczkowski","year":"2019","journal-title":"Regen. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s13287-020-02130-7","article-title":"Human mesenchymal stem cell therapy promotes retinal ganglion cell survival and target reconnection after optic nerve crush in adult rats","volume":"12","author":"Vasques","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Ding, S.L.S., Kumar, S., and Mok, P.L. (2017). Cellular Reparative Mechanisms of Mesenchymal Stem Cells for Retinal Diseases. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18081406"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Theerakittayakorn, K., Thi Nguyen, H., Musika, J., Kunkanjanawan, H., Imsoonthornruksa, S., Somredngan, S., Ketudat-Cairns, M., and Parnpai, R. (2020). Differentiation Induction of Human Stem Cells for Corneal Epithelial Regeneration. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21217834"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/nrm3043","article-title":"Dedifferentiation, transdifferentiation and reprogramming: Three routes to regeneration","volume":"12","author":"Jopling","year":"2011","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_85","first-page":"99","article-title":"Differentiation of rabbit bone marrow mesenchymal stem cells into corneal epithelial cells in vivo and ex vivo","volume":"15","author":"Gu","year":"2009","journal-title":"Mol. Vis."},{"key":"ref_86","first-page":"1304","article-title":"Reconstruction of the corneal epithelium with induced marrow mesenchymal stem cells in rats","volume":"16","author":"Jiang","year":"2010","journal-title":"Mol. Vis."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2868","DOI":"10.1634\/stemcells.2005-0636","article-title":"Functional Neuronal Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells","volume":"24","author":"Tropel","year":"2006","journal-title":"Stem Cells"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"7742","DOI":"10.1523\/JNEUROSCI.23-21-07742.2003","article-title":"Differentiation of Marrow Stromal Cells into Photoreceptors in the Rat Eye","volume":"23","author":"Kicic","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.yexcr.2015.02.001","article-title":"Retinal differentiation of human bone marrow-derived stem cells by co-culture with retinal pigment epithelium in vitro","volume":"333","author":"Mathivanan","year":"2015","journal-title":"Exp. Cell Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.aanat.2016.11.010","article-title":"Overview of retinal differentiation potential of mesenchymal stem cells: A promising approach for retinal cell therapy","volume":"210","author":"Salehi","year":"2017","journal-title":"Ann. Anat. Anat. Anz."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3742","DOI":"10.1167\/iovs.08-3314","article-title":"Effects of Bone Marrow Mesenchymal Stem Cell Transplantation on Light-Damaged Retina","volume":"51","author":"Zhang","year":"2010","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.bbrc.2004.02.111","article-title":"Bone marrow stromal cells produce nerve growth factor and glial cell line-derived neurotrophic factors","volume":"316","author":"Aguiar","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1590\/S0004-27492013000200010","article-title":"Light-induced retinal injury enhanced neurotrophins secretion and neurotrophic effect of mesenchymal stem cells in vitro","volume":"76","author":"Xu","year":"2013","journal-title":"Arq. Bras. Oftalmol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.expneurol.2008.12.028","article-title":"Umbilical cord blood mesenchymal stromal cells are neuroprotective and promote regeneration in a rat optic tract model","volume":"216","author":"Zwart","year":"2009","journal-title":"Exp. Neurol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41581-018-0023-5","article-title":"Immunoregulatory mechanisms of mesenchymal stem and stromal cells in inflammatory diseases","volume":"14","author":"Shi","year":"2018","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.jcyt.2015.12.002","article-title":"Mesenchymal stromal cell\u2013mediated neuroprotection and functional preservation of retinal ganglion cells in a rodent model of glaucoma","volume":"18","author":"Mead","year":"2016","journal-title":"Cytotherapy"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3104","DOI":"10.3892\/mmr.2016.5621","article-title":"Mesenchymal stem cells in corneal neovascularization: Comparison of different application routes","volume":"14","author":"Ghazaryan","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s10456-016-9497-6","article-title":"Bone marrow-derived cells in ocular neovascularization: Contribution and mechanisms","volume":"19","author":"Gao","year":"2016","journal-title":"Angiogenesis"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.3727\/096368915X688263","article-title":"Retinal Angiogenesis Effects of TGF-\u03b21 and Paracrine Factors Secreted from Human Placental Stem Cells in Response to a Pathological Environment","volume":"25","author":"Kim","year":"2016","journal-title":"Cell Transplant."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1186\/s13287-020-01702-x","article-title":"Extracellular vesicles derived from human ES-MSCs protect retinal ganglion cells and preserve retinal function in a rodent model of optic nerve injury","volume":"11","author":"Seyedrazizadeh","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.3727\/096368913X667709","article-title":"Paracrine Mechanisms of Mesenchymal Stem Cell-Based Therapy: Current Status and Perspectives","volume":"23","author":"Liang","year":"2014","journal-title":"Cell Transplant."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1002\/sctm.16-0428","article-title":"Bone Marrow-Derived Mesenchymal Stem Cells-Derived Exosomes Promote Survival of Retinal Ganglion Cells Through miRNA-Dependent Mechanisms","volume":"6","author":"Mead","year":"2017","journal-title":"Stem Cells Transl. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s12929-018-0429-1","article-title":"Regenerative abilities of mesenchymal stem cells through mitochondrial transfer","volume":"25","author":"Paliwal","year":"2018","journal-title":"J. Biomed. Sci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1167\/iovs.61.8.38","article-title":"Development of Animal Models for Lens and Corneal Diseases Using N-Methyl-N-Nitrosourea","volume":"61","author":"Qu","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Collin, G.B., Gogna, N., Chang, B., Damkham, N., Pinkney, J., Hyde, L.F., Stone, L., Naggert, J.K., Nishina, P.M., and Krebs, M.P. (2020). Mouse Models of Inherited Retinal Degeneration with Photoreceptor Cell Loss. Cells, 9.","DOI":"10.3390\/cells9040931"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1242\/dmm.017236","article-title":"Cellular models and therapies for age-related macular degeneration","volume":"8","author":"Forest","year":"2015","journal-title":"Dis. Model. Mech."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1167\/iovs.14-15415","article-title":"Intravitreal Autologous Bone Marrow CD34+ Cell Therapy for Ischemic and Degenerative Retinal Disorders: Preliminary Phase 1 Clinical Trial Findings","volume":"56","author":"Park","year":"2014","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1097\/IAE.0b013e3181f9c242","article-title":"Intravitreal Injection of Autologous Bone Marrow\u2013Derived Mononuclear Cells for Hereditary Retinal Dystrophy","volume":"31","author":"Siqueira","year":"2011","journal-title":"Retina"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1186\/s13287-016-0432-y","article-title":"Subretinal adipose tissue-derived mesenchymal stem cell implantation in advanced stage retinitis pigmentosa: A phase I clinical safety study","volume":"7","author":"Oner","year":"2016","journal-title":"Stem Cell Res. Ther."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/5584_2018_219","article-title":"Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Eye Diseases","volume":"1089","author":"Harrell","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1002\/stem.674","article-title":"Optic Vesicle-like Structures Derived from Human Pluripotent Stem Cells Facilitate a Customized Approach to Retinal Disease Treatment","volume":"29","author":"Meyer","year":"2011","journal-title":"Stem Cells"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"16698","DOI":"10.1073\/pnas.0905245106","article-title":"Modeling early retinal development with human embryonic and induced pluripotent stem cells","volume":"106","author":"Meyer","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"6282","DOI":"10.1167\/iovs.12-9721","article-title":"Using Flow Cytometry to Compare the Dynamics of Photoreceptor Outer Segment Phagocytosis in iPS-Derived RPE Cells","volume":"53","author":"Westenskow","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.exer.2004.11.001","article-title":"Photoreceptor differentiation and integration of retinal progenitor cells transplanted into transgenic rats","volume":"80","author":"Qiu","year":"2005","journal-title":"Exp. Eye Res."},{"key":"ref_115","first-page":"448","article-title":"Differentiation of human embryonic retinal cells in vitro","volume":"40","author":"Yu","year":"2004","journal-title":"Chin. J. Ophthalmol."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/12\/5\/708\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:08:12Z","timestamp":1760137692000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/12\/5\/708"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,9]]},"references-count":115,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["life12050708"],"URL":"https:\/\/doi.org\/10.3390\/life12050708","relation":{},"ISSN":["2075-1729"],"issn-type":[{"type":"electronic","value":"2075-1729"}],"subject":[],"published":{"date-parts":[[2022,5,9]]}}}