Epithelial stem cells of the eye surface

Abstract

Objectives: Epithelial stem cells of the eye surface, of the cornea and of the conjunctiva, have the ability to give rise to self renewal and progeny production of differentiated cells with no apparent limit. The two epithelia are separated from each other by the transition zone of the limbus. The mechanisms adopted by stem cells of the two epithelia to accomplish their different characteristics, and how their survival, replacement and unequal division that generates differentiated progeny formation are controlled, are complex and still poorly understood. They can be learned only by understanding how stem cells/progenitors are regulated by their neighbouring cells, that may themselves be differently unspecialised, forming particular microenvironments, known as 'niches'. Stem cells operate by signals and a variety of intercellular interactions and extracellular substrates with adjacent cells in the niche. Technical advances are now making it possible to identify zones in the corneal limbus and conjunctiva that can house stem cells, to isolate and expand them ex vivo and to control their behaviour creating optimal niche conditions. With improvements in biotechnology, regenerative cornea and conjunctiva transplantation using adult epithelial stem cells becomes now a reality.

Results and conclusions: Here we review our current understanding of stem cell niches and illustrate recent significant progress for identification and characterization of adult epithelial stem cells/progenitors at cellular, molecular and mechanistic levels, improvement in cell culture techniques for their selective expansion ex vivo and prospects for a variety of therapeutic applications.

Figure 1

Isolation and expansion of basal corneal cells and demonstration of their stem/progenitor properties. Epithelial cells recovered from fragments of limbal tissue, after enzymatic treatment in the presence of feeder post‐mitotic cells, NIH‐3T3 form clones of epithelial cells p63 (a) and CK‐19 positive (b), negative for CK‐3 (c). These cells, transferred to a collagen matrix containing human corneal stromal fibrobasts (line HPC‐33). Like feeder cells, these form superimposed cohesive layers of non‐keratinized cells capable of differentiation (d), and of maintaining a layer of elements p63 positive (basal) (e), CK‐19 positive (basal and epibasal) (f) and CK‐3 positive (epibasal) (g). Basal corneal cells on collagen matrix without HPC‐33 feeder cells fail to form a multilayered epithelium and remain as a monolayered sheet only (not shown) (enlargement of the original: b, 200×; a, c, d, e, f and g, 200×) (Papini et al. 2005).