Localization of candidate stem and progenitor cell markers within the human cornea, limbus, and bulbar conjunctiva in vivo and in cell culture

Abstract

Corneal diseases are some of the most prevalent causes of blindness worldwide. While the most common treatment for corneal blindness is the transplantation of cadaver corneas, expanded limbal stem cells are finding recent application. Unknown, however, is the identity of the actual repopulating stem cell fraction utilized in both treatments and the critical factors governing successful engraftment and repopulation. In order to localize potential stem cell populations in vivo, we have immunohistochemically mapped a battery of candidate stem and progenitor cell markers including c-Kit and other growth factor receptors, nuclear markers including ⌬Np63, as well as adhesion factors across the cornea and distal sclera. Cell populations that differentially and specifically stained for some of these markers include the basal and superficial limbal/conjunctival epithelium and scattered cells within the substantia propria of the bulbar conjunctiva. We have also determined that the culture of differentiated cornea epithelial cells as dissociated and explant cultures induces the expression of several markers previously characterized as candidate limbal stem cell markers. This study provides a foundation to explore candidate corneal stem cell populations. As well, we show that expression of traditional stem cell markers may not be reliable indicator of stem cell content during limbal stem cell expansion in vitro and could contribute to the variable success rates of corneal stem cell transplantation. Anat Rec Part A, 288A: 921-931, 2006.

An Update on Ocular Surface Epithelial Stem Cells: Cornea and Conjunctiva

“…Other immunohistological studies also suggest the presence of p63 and ABCG2 positive cells in the bulbar conjunctival epithelium [25]. Clinical observations also indicate that the CjSCs are located in the fornix and/or in the bulbar conjunctiva [26].…”

Putative Rabbit Conjunctival Epithelial Stem/Progenitor Cells Preferentially Reside in Palpebral Conjunctiva

“…[1][2][3][4] Therefore, the identification of conjunctival epithelial stem cells relies mainly on the common features of stem cells, such as the proliferative capability and colony-forming ability in vitro, or the identification of slow-cycling cells with [ 3 H]ThR-or BrdU-retaining methods in vivo.…”

Culturing of Retinal Pigment Epithelium Cells

“…As a rule, these cells can only be isolated from postmortem tissue, which limits their viability and further decreases the number of cultivable cells. Except for some few ocular progenitor cells that have been characterized in recent years [2,3], most types of ocular cells are generally terminally differentiated and postmitotic in vivo, which means that proliferation in vitro resembles an atypical state. The cells have to re-enter the cell cycle, and this may lead not only to proliferation, but also to a loss of differentiated characteristics, since differentiation of these cells is basically linked to cell cycle arrest.…”