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Universal corneal epithelial-like cells derived from human embryonic stem cells for cellularization of a corneal scaffold
Yang J.; Park J.W.; Zheng D.; Xu R.-H.
2018-09-01
Source PublicationTranslational Vision Science and Technology
ISSN21642591
Volume7Issue:5
Abstract

Purpose: We generated universal corneal epithelial cells (CEC) from human embryonic stem cells (hESC) by genetically removing human leukocyte antigens (HLA) class I from the cell surface. Methods: The serum-free, growth factor-free, and defined medium E6 was used to differentiate hESC to CEC. Decellularized murine corneas were recellularized with hESC-derived CEC. Using CRISPR/Cas9, β-2-microglobulin (B2M) was deleted in hESC to block the assembly of HLA class-I antigens on the cell surface to generate B2M CEC. Results: E6 alone was sufficient to allow hESC differentiation to CEC. A time-course analysis of the global gene expression of the differentiating cells indicates that the differentiation closely resembles the corneal development in vivo. The hESC-CEC were highly proliferative, and could form multilayer epithelium in decellularized murine cornea, retain its transparency, and form intact tight junctions on its surface. As reported before, B2M knockout led to the absence of HLA class-I on the cell surface of hESC and subsequently derived CEC following stimulation with inflammatory factors. Moreover, B2M CEC, following transplantation into mouse eyes, caused less T-cell infiltration in the limbal region of the eye than the wild-type control. Conclusions: CEC can be derived from hESC via a novel and simple protocol free of any proteins, hESC-CEC seeded on decellularized animal cornea form tight junctions and allow light transmittance, and B2M CEC are hypoimmunogenic both in vitro and in vivo. Translational Relevance: B2M hESC-CEC can be an unlimited and universal therapy for corneal repair in patients of any HLA type.

KeywordB2m Knockout Corneal Epithelial Cells Decellularized Cornea Differentiation Human Embryonic Stem Cells Immunogenicity
DOI10.1167/tvst.7.5.23
URLView the original
Indexed BySCI
Language英语
WOS Research AreaOphthalmology
WOS SubjectOphthalmology
WOS IDWOS:000447352100011
PublisherASSOC RESEARCH VISION OPHTHALMOLOGY INC, 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
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Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorXu R.-H.
AffiliationCenter of Reproduction, Development & Aging, and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau, China
First Author AffilicationFaculty of Health Sciences
Corresponding Author AffilicationFaculty of Health Sciences
Recommended Citation
GB/T 7714
Yang J.,Park J.W.,Zheng D.,et al. Universal corneal epithelial-like cells derived from human embryonic stem cells for cellularization of a corneal scaffold[J]. Translational Vision Science and Technology,2018,7(5).
APA Yang J.,Park J.W.,Zheng D.,&Xu R.-H..(2018).Universal corneal epithelial-like cells derived from human embryonic stem cells for cellularization of a corneal scaffold.Translational Vision Science and Technology,7(5).
MLA Yang J.,et al."Universal corneal epithelial-like cells derived from human embryonic stem cells for cellularization of a corneal scaffold".Translational Vision Science and Technology 7.5(2018).
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