These observations lend further support to the importance of the amniotic membrane

As such, limbal stem cell transplantation has been applied in both clinical and animal studies to repair and/or regenerate the corneal epithelium in eyes that have been traumatized as a result of the destruction of limbal SCs. Multiple mechanisms have been proposed for the regulation and maintenance of SCs in the limbus of the cornea. The preferred hypothesis is that adult SCs are regulated by their niche, a special microenvironment for the maintenance of limbal stem cells in an undifferentiated state, which consists of unique limbal stromal cells and the underlying BM. Ultimately, limbal SCs contribute to the repair and regeneration of transparent corneas. Previous studies have shown that the amniotic membrane is able to provide a niche environment for limbal SC proliferation and differentiation: limited in number of limbal SCs could be expanded ex vivo to become numerous stem/progenitor cells that are p63-positive and Piroctone Olamine BrdU-label retentive. Through vivo expansion, these SC-like cells can be successfully grown on the human cornea and thereby help to maintain its clarity as well as the homeostasis between corneal epithelium proliferation and differentiation for years. These observations lend further support to the importance of the amniotic membrane as a unique niche environment for the maintenance and expansion of limbal SCs in vitro. The BM of a diseased or traumatized cornea is often disrupted, which subsequently leads to changes in epithelial phenotype. For example, an epithelial plug was once found in the epithelial wound created by radial keratotomy of the excised corneal buttons obtained after penetrating keratoplasty. Examination of keratoconus corneas by confocal microscopy showed that the epithelial cells assumed a different morphology and phenotype in comparison to normal corneas. Histological examinations have also revealed that the Bowman��s membrane and BM are fragmented and Nortriptyline disrupted in keratoconus corneas. Furthermore, adhesion of basal epithelial cells to the extracellular matrix is mediated by several classes of receptor, the most extensively characterized being integrins.

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