Abstract
Limbal epithelial stem/progenitor cells (LSCs) reside in a niche that contains finely tuned balances of various signaling pathways including Wnt, Notch, BMP, Shh, YAP, and TGFβ. The activation or inhibition of these pathways is frequently dependent on the interactions of LSCs with various niche cell types and extracellular substrates. In addition to receiving molecular signals from growth factors, cytokines, and other soluble molecules, LSCs also respond to their surrounding physical structure via mechanotransduction, interaction with the ECM, and interactions with other cell types. Damage to LSCs or their niche leads to limbal stem cell deficiency (LSCD). The field of LSCD treatment would greatly benefit from an understanding of the molecular regulation of LSCs in vitro and in vivo. This review synthesizes current literature around the niche factors and signaling pathways that influence LSC function. Future development of LSCD therapies should consider all these niche factors to achieve improved long-term restoration of the LSC population.
Highlights
Light first enters the eye through the cornea, the outermost transparent layer, which is important both as an environmental barrier and in the refraction of light
While recent reviews have been focused on the limbal niche structure [27,28], diseases involving Limbal epithelial stem/progenitor cells (LSCs) function [29], and advances in LSC bioengineering and limbal stem cell deficiency (LSCD) diagnosis [22], here we present an in-depth analysis of molecular regulation and the influence of surrounding physical properties governing the fate of LSCs
LSCs are regulated by carefully tuned balances of various signaling pathways, and the activation or inhibition of these pathways is frequently dependent on the interactions of LSCs with various niche cell types and extracellular substrates
Summary
Light first enters the eye through the cornea, the outermost transparent layer, which is important both as an environmental barrier and in the refraction of light. The majority of LSCD cases are either unilateral or sub-total bilateral LSCD, as residual LSCs could be found in eyes with clinical features of total LSCD [21] In these patients, transplantation of autologous LSCs, either by cultivated LSCs or direct tissue transplantation, is a viable and preferred option [22,23]. This review will discuss the current findings on the integration of molecular and mechanical signaling factors that regulate LSC quiescence, self-renewal, differentiation, migration, and proliferation in vivo and in vitro. While recent reviews have been focused on the limbal niche structure [27,28], diseases involving LSC function [29], and advances in LSC bioengineering and LSCD diagnosis [22], here we present an in-depth analysis of molecular regulation and the influence of surrounding physical properties governing the fate of LSCs
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