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F.E. Kruse, T. Dietrich, B. Seitz, U. Schlötzer–Schrehardt; Defining the Limbal Stem Cell Niche: The Role of Extracellular Matrix Components . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2081.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: A specialized microenvironment (niche) is one of the key prerequisites for a stem cell phenotype. In contrast to other tissues, the niche parameters of corneal epithelial stem cells have not been defined. We therefore wanted to characterize the role of basement membrane components in the generation of a microenvironmental niche for human corneal epithelial stem cells. Methods: Corneal sections from 20 donors (age 61–91 years, post mortem times 1.5–15 hours) were stained by indirect immunofluorescence using a broad panel of antibodies against integral and associated basement membrane components. In double labeling experiments, commercially available antibodies against putative stem cell and differentiation markers, e.g. p63, ABCG–2, connexin 43 (Cx43), were used in addition. Results: Basement membrane components that were homogenously distributed in ocular surface epithelia include laminin–1, laminin–5, laminin (α3, α5, ß3, γ1, γ2, and γ3 chains), nidogen–1, perlecan, collagen type IV (α5 and α6 chains), collagen types VII, XV, XVII, and XVIII, endostatin, fibronectin, fibrillin–2, matrilin–2 and –4, bamacan, and thrombospondin–4. As compared to the corneal and conjunctival basement membrane, the limbal basement membrane showed increased immunoreactivity for agrin, BM40/SPARC, laminin (α1, α2 and ß1 chains), collagen type IV (α1 and α2 chains), nidogen–2, collagen type XVI, versican, and tenascin–C, whereas reduced immunoreactivity was observed for collagen type IV (α3 and α4 chains), collagen type V, fibulin–2, fibrillin–1, and clusterin. Patchy staining patterns of agrin, BM40/SPARC, tenascin–C, and versican appeared to co–localize with p63/ABCG–2–positive and Cx43–negative cell clusters in the limbal basal epithelium. No evidence was found for the presence of laminin α4 and ß2, fibulin–1,–3,–4, and –5, matrilin–3, Smoc–1 and –2, testican–1,–2, and –3, in basement membranes of ocular surface epithelia. Conclusions: Basement membrane heterogeneity in the limbal area may be involved in providing a unique microenvironment for corneal stem cells. The characteristics of this microenvironment could serve as tools for their selective enrichment and in vitro expansion.
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