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To date, there are no efficient therapeutic approaches to treat this condition. In the present study, we aimed to investigate whether human amniotic epithelial stem cells (hAESCs) could serve as a novel seed cell source of photoreceptors for therapy. Here, a two\u2013step treatment with combined Wnt, Nodal, and BMP inhibitors, followed by another cocktail of retinoic acid, taurine, and noggin induced photoreceptor\u2013like cell differentiation of hAESCs. The differentiated cells demonstrated the morphology and signature marker expression of native photoreceptor cells and, intriguingly, bore very low levels of major histocompatibility complex (MHC) class II molecules and a high level of non\u2013classical MHC class I molecule HLA\u2013G. Importantly, subretinal transplantation of the hAESCs\u2013derived PR\u2013like cells leads to partial restoration of visual function and retinal structure in Royal College of Surgeon (RCS) rats, the classic preclinical model of retinal degeneration. Together, our results reveal hAESCs as a potential source of functional photoreceptor cells; the hAESCs\u2013derived photoreceptor\u2013like cells could be a promising cell\u2013replacement candidate for therapy of retinal degeneration diseases.<\/jats:p>","DOI":"10.3390\/ijms23158722","type":"journal-article","created":{"date-parts":[[2022,8,7]],"date-time":"2022-08-07T22:51:46Z","timestamp":1659912706000},"page":"8722","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Repair of Retinal Degeneration by Human Amniotic Epithelial Stem Cell\u2013Derived Photoreceptor\u2013like Cells"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7434-674X","authenticated-orcid":false,"given":"Jinying","family":"Li","sequence":"first","affiliation":[{"name":"MOE Laboratory of Biosystems Homeostasis & Protection, College of Life Sciences, Zhejiang University, Hangzhou 310058, 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