title: Existence of Neural Crest-Derived Progenitor Cells in Normal and Fuchs Endothelial Dystrophy Corneal Endothelium.
abstract: Human corneal endothelial cells are derived from neural crest and because of postmitotic arrest lack competence to repair cell loss from trauma, aging, and degenerative disorders such as Fuchs endothelial corneal dystrophy (FECD). Herein, we identified a rapidly proliferating subpopulation of cells from the corneal endothelium of adult normal and FECD donors that exhibited features of neural crest-derived progenitor (NCDP) cells by showing absence of senescence with passaging, propensity to form spheres, and increased colony forming efficacy compared with the primary cells. The collective expression of stem cell-related genes SOX2, OCT4, LGR5, TP63 (p63), as well as neural crest marker genes PSIP1 (p75(NTR)), PAX3, SOX9, AP2B1 (AP-2β), and NES, generated a phenotypic footprint of endothelial NCDPs. NCDPs displayed multipotency by differentiating into microtubule-associated protein 2, β-III tubulin, and glial fibrillary acidic protein positive neurons and into p75(NTR)-positive human corneal endothelial cells that exhibited transendothelial resistance of functional endothelium. In conclusion, we found that mitotically incompetent ocular tissue cells contain adult NCDPs that exhibit a profile of transcription factors regulating multipotency and neural crest progenitor characteristics. Identification of normal NCDPs in FECD-affected endothelium holds promise for potential autologous cell therapies.
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear, Boston, Massachusetts.
authors.forename: Kishore Reddy
authors.initials: KR
authors.lastname: Katikireddy
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear, Boston, Massachusetts; AbbVie Deutschland GmbH & Co KG, Ludwigshafen, Germany.
authors.forename: Thore
authors.initials: T
authors.lastname: Schmedt
authors.affiliation: Cornea Research Foundation of America, Indianapolis, Indiana.
authors.forename: Marianne O
authors.initials: MO
authors.lastname: Price
authors.affiliation: Price Vision Group, Indianapolis, Indiana.
authors.forename: Francis W
authors.initials: FW
authors.lastname: Price
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear, Boston, Massachusetts. Electronic address: ula_jurkunas@meei.harvard.edu.
authors.forename: Ula V
authors.initials: UV
authors.lastname: Jurkunas
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D066026:Endothelial Progenitor Cells / Q000378:metabolism* / Q000473:pathology; D004728:Endothelium, Corneal / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005642:Fuchs' Endothelial Dystrophy / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009432:Neural Crest / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D014404:Tubulin
chemical_list: D015415:Biomarkers; C489788:MAP2 protein, human; D008869:Microtubule-Associated Proteins; D014404:Tubulin