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Currently, there is no treatment to replace the macula. Addressing this unmet need, we employed control isogenic and hypoimmunogenic induced pluripotent stem cell lines to generate spontaneously polarized retinal sheets (RSs). RSs were enriched in retinal progenitor and cone precursor cells, which could differentiate into mature S- and M\/L-cones in long-term cultures. Single-cell RNA-seq analysis showed that RSs recapitulate the ontogeny of the developing human retina. Isolation of neural rosettes for sub-retinal transplantation effectively eliminated unwanted cells such as RPE cells. In a porcine model of chemically induced retinal degeneration, grafts integrated the host retina and formed a new, yet immature, photoreceptor layer. In one transplanted animal, functional and immunohistochemical assays suggest that grafts exhibited responsiveness to light stimuli and established putative synaptic connections with host bipolar neurons. This study underscores the potential and challenges of RSs for clinical applications.<\/jats:p>","DOI":"10.1242\/dev.203071","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T10:02:58Z","timestamp":1733392978000},"source":"Crossref","is-referenced-by-count":4,"title":["Molecular characterization and sub-retinal transplantation of hypoimmunogenic human retinal sheets in a minipig model of severe photoreceptor degeneration"],"prefix":"10.1242","volume":"151","author":[{"given":"Andrea","family":"Barabino","sequence":"first","affiliation":[{"name":"H\u00f4pital Maisonneuve-Rosemont 1 Stem Cell and Developmental Biology Laboratory , , 5690 Boul. Rosemont, Montreal, QC H1T 2H2 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Mellal","sequence":"additional","affiliation":[{"name":"H\u00f4pital Maisonneuve-Rosemont 1 Stem Cell and Developmental Biology Laboratory , , 5690 Boul. 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