A supramolecular look at microenvironmental regulation of limbal epithelial stem cells and the differentiation of their progeny

Abstract

Various approaches have been taken to improve our knowledge of the microenvironmental regulation of limbal epithelial stem cells. Researchers have extensively investigated the roles of growth factors, survival factors, cytokines, enzymes, and permeable molecules secreted by the limbal cells. However, recent evidence suggests that stem cell fate (i.e., self-renewal or differentiation) can also be influenced by biophysical and mechanical cues related to the supramolecular organization and the liquid crystalline (mesophase) nature of the stromal extracellular matrix. These cues can be sensed by stem cells and transduced into intracellular biochemical and functional responses, a process known as mechanotransduction. The objective of this review is to offer perspectives on the supramolecular microenvironmental regulation of limbal epithelial stem cells and the differentiation of their progeny.

Regulation of Limbal Epithelial Stem Cells: Importance of the Niche

“…In culture, corneal epithelial cells are able to conform to the topography of the surface on which they are grown [ 122 , 123 , 124 ], and the components of the culture media can influence the ability of the corneal epithelial cells to conform to their substrate [ 125 ]. In addition, the response of LSCs to growth factors is influenced by their surrounding substrates [ 121 , 126 ]. The ECM on which LSCs grow has a considerable influence on the proliferative potential of stem cells [ 55 , 127 , 128 ].…”