Corneal stem cells and their origins: significance in developmental biology.

Adult corneal stem cells (SCs) have been the subject of substantial research over the past 2 decades, with promising clinical applications being devised, refined, and tried. However, there have been few studies on the early development of these cells in humans, perhaps due to ethical and practical constraints. This review highlights work that has yielded significant insights from developmental studies in the cornea and other SC repositories. This field merits further research to improve our current knowledge of the origin of SCs, their location, phenotype, function, and niche structure, as well as providing fresh insight into the pathogenesis of congenital diseases and new therapeutic avenues for treating a range of blinding corneal diseases.

Stem cell activity in the developing human cornea.

The adult cornea harbors stem cells (SCs) in its periphery, in a niche known as the limbus. Over the past 2 decades there has been substantial research into these adult corneal SCs, their limbal niche, and their therapeutic applications. However, few studies have investigated how this niche and its SCs develop in humans. To better characterize this development, human fetal corneas from 8.5- to 22-weeks'-gestation (n = 173), neonatal (n = 2), and adult (n = 10) specimens were obtained. Histological and immunohistochemical assessments were conducted to determine embryological changes and expression of developmental and SC-related genes. Fresh fetal corneas were explanted to propagate corneal progenitors and cells characterized using reverse transcription-polymerase chain reaction, immunohistochemistry, flow cytometry, and colony-forming assays. A novel "ridge-like" structure was identified, circumscribing the fetal cornea, which we hypothesize represents the rudimentary SC niche. Immunohistochemistry disclosed "stem-like" cells across the cornea, becoming confined to this ridge with increasing gestational age. In addition, for the first time, pure long-term cultures of fetal corneal epithelium, which displayed phenotypical and functional properties similar to those of adult limbal SCs, were established. Optimization of culture techniques and purification of this SC population will allow for further investigation of their proliferative ability, with potential research and clinical applications. This study expands our understanding of limbal niche development and opens new avenues for investigation.