Limbal stem cells maintenance in the in vitro cultivation

Abstract

The maintenance of a healthy corneal epithelium under both normal and wound healing conditions is achieved by a population of stem cells (SC) located in the basal epithelium at the corneoscleral limbus. These cells, also called limbal epithelial stem cells (limbal SC) retain their self-renewal and maintain their proliferative capacity. Limbal stem cell can be expanded ex vivo on amniotic membrane and used for transplantation to the patients who suffer from limbal stem cell deficiency. However, this technique still has drawbacks; particularly stem cells lose their properties that limit the use for transplantation. Therefore, the studying about limbal stem cells niche and developing a culture system that similar to their niche are required for maintenance limbal stem cell in long term culture by activating Wnt signaling in limbal stem cells and creating Bone morphogenesis protein (BMP) antagonists expression feeder cells. These molecules have been showed a potential role in the proliferation and the maintenance of other epithelial stem cells in their niche. We founded BMP antagonist, Gremlin-1, prolonged cell cycle of limbal stem cell through down-regulation of cyclin-dependent kinase inhibitor, p27 [subscript kip1] and activation of Wnt signaling promoted proliferation of limbal stem cells.