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However, global shortage of donor tissues has driven the development cell-based therapeutics. With the capacity to propagate regulatory compliant human corneal endothelial cells (CEnCs), this study evaluated the functionality of propagated CEnCs delivered via tissue-engineered endothelial keratoplasty (TE-EK) or corneal endothelial cell injection (CE-CI) within a rabbit model of bullous keratopathy. For animals with TE-EK grafts, central corneal thickness (CCT) increased to &gt;1000 \u03bcm post-operatively. Gradual thinning with improvements in corneal clarity was observed from week 1. CCT at week 3 was 484.3\u2009\u00b1\u200973.7 \u03bcm. In rabbits with CE-CI, corneal clarity was maintained throughout, and CCT at week 3 was 582.5\u2009\u00b1\u2009171.5 \u03bcm. Control corneas remained significantly edematous throughout the study period compared to their respective experimental groups (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Characterization of excised corneas showed a monolayer with heterogeneously shaped CEnCs in both TE-EK and CE-CI groups. Immunohistochemistry demonstrated reactivity to anti-human specific nuclei antibody attributing corneal recovery to the functional human CEnCs. This study showed that regulatory compliant cell-based therapy for corneal endothelial dysfunction can be delivered by both TE-EK and CE-CI, and holds great promise as an alternative to traditional corneal transplantation.<\/jats:p>","DOI":"10.1038\/s41598-019-42493-3","type":"journal-article","created":{"date-parts":[[2019,4,15]],"date-time":"2019-04-15T10:02:52Z","timestamp":1555322572000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":77,"title":["Functional Evaluation of Two Corneal Endothelial Cell-Based Therapies: Tissue-Engineered Construct and Cell Injection"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5387-4209","authenticated-orcid":false,"given":"Gary S. 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