title: Keratin 14 Expression in Epithelial Progenitor Cells of the Developing Human Cornea.
abstract: A healthy and transparent cornea is essential for exquisite vision. During adulthood, its epithelium is constantly replenished through the activity of its stem cells (SCs). Precisely when these cells develop and their distribution across the ocular surface remain incompletely characterized in man. We postulated that the human fetal cornea harbors SCs that can be identified with keratin (K) 14 and αv-integrin, two markers we and others previously used to identify their adult counterparts. Immunofluorescence, cell culture, quantitative real-time polymerase chain reaction (qRT-PCR), and colony-forming assays were performed on fetal and adult biomaterial to locate progenitors and establish their phenotypic and functional properties. K14 was used to map the spatiotemporal distribution of precursor cell activity across the developing cornea, divulging a dynamic pattern of vertical and horizontal consolidated expression with increasing gestational age. K14 was coexpressed with αv-integrin in fetal and adult corneas and cultured corneolimbal epithelium, and colony-forming efficiency (an indicator of SC activity) was similar in cells from both sources. Finally, fetal cells were adherent, grew well, and maintained a K14 phenotype on contact lenses, a substrate we previously used to deliver cells to patients with blinding corneal disease. This study provides valuable insights into the development of the cornea, including the formation of the SC repository, the distribution of these cells across the ocular surface, and a preliminary attempt at harnessing, phenotyping, and functionally characterizing these cells. Future studies will focus on isolating fetal SCs to determine their utility as an alternative cell therapy for patients suffering from corneal blindness.
authors.affiliation: 1 Ocular Diseases Research Group, School of Medical Sciences, University of New South Wales , Sydney, Australia .
authors.forename: Yas
authors.initials: Y
authors.lastname: Eghtedari
authors.affiliation: 1 Ocular Diseases Research Group, School of Medical Sciences, University of New South Wales , Sydney, Australia .
authors.forename: Alexander
authors.initials: A
authors.lastname: Richardson
authors.affiliation: 1 Ocular Diseases Research Group, School of Medical Sciences, University of New South Wales , Sydney, Australia .
authors.forename: Kelly
authors.initials: K
authors.lastname: Mai
authors.affiliation: 2 Neuroinflammation Group, Faculty of Medicine & Health Sciences, Macquarie University , Sydney, Australia .
authors.forename: Benjamin
authors.initials: B
authors.lastname: Heng
authors.affiliation: 2 Neuroinflammation Group, Faculty of Medicine & Health Sciences, Macquarie University , Sydney, Australia .
authors.forename: Gilles J
authors.initials: GJ
authors.lastname: Guillemin
authors.affiliation: 1 Ocular Diseases Research Group, School of Medical Sciences, University of New South Wales , Sydney, Australia .
authors.forename: Denis
authors.initials: D
authors.lastname: Wakefield
authors.affiliation: 1 Ocular Diseases Research Group, School of Medical Sciences, University of New South Wales , Sydney, Australia .
authors.forename: Nick
authors.initials: N
authors.lastname: Di Girolamo
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D003261:Contact Lenses; D019573:Epithelium, Corneal / Q000166:cytology* / Q000196:embryology*; D005333:Fetus / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D053547:Keratin-14 / Q000235:genetics* / Q000378:metabolism; D016850:Limbus Corneae / Q000166:cytology; D010641:Phenotype; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D053547:Keratin-14