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Helen Makarenkova, Anastasia Gromova, Dmitry Voronov, Miya Yoshida, Robyn Meech; Identification of Novel Epithelial Stem/Progenitor Cell Population in Murine Uninjured Lacrimal Gland. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2190.
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© ARVO (1962-2015); The Authors (2016-present)
The tear-deficient dry eye condition is an ocular-surface dysfunction characterized by a lack of tear secretion from the lacrimal glands. The development of strategies to isolate and manipulate lacrimal gland stem/progenitor cells from adult lacrimal gland tissue brings great promise for the design of cell replacement therapies for patients with dry eye conditions.
In this study we have examined murine lacrimal gland cell populations using ex vivo lacrimal gland cultures, Fluorescence Activated Cell Sorting (FACS), cell re-aggregation and clonal efficiency assays, immunostaining, q-RT-PCR microarrays, and in vivo lacrimal gland regeneration assay.
Several recent studies indicate that multipotent progenitor cells are present in the lacrimal gland and are involved in lacrimal gland regeneration. Lacrimal gland epithelial lineage is represented by ductal, myoepithelial, and acinar cells that produce, modify, and secrete the aqueous tear film layer. Analysis of stem cell-associated transcription factor expression in separated lacrimal gland epithelial and mesenchymal lineages showed that epithelial cells express several epithelial-specific factors including Sox2, Sox6, and Sox9 (stem cell markers), Foxp1 (forkhead transcription factor-1, regulator of epithelial injury response), Six2, (Sine oculis-related homeobox), and Runx1 and 2 (runt family transcription factors). Moreover, expression of Runx1 was strongly upregulated in regenerating lacrimal gland and this increase correlated with increase in expression of epithelial stem/progenitor marker cytokeratin-5, suggesting that Runx1 is important for lacrimal gland regeneration and stem/progenitor cells expansion. Cell population analysis by FACS, 3D re-aggregate cultures and clonal efficiency assay showed that c-kitdim/EpCam+/CD34-/Sca-CD45- cells expressed the pluripotency marker Oct-4 (octamer-binding transcription factor 4) and had elevated Runx1 expression and formed branched structures expressing E-cadherin in 3D cultures, suggesting that these cells may be able to regenerate the epithelial component of the gland.
These data support the existence of epithelial-specific stem/progenitor cells and a role for Runx1 in their regulation. We anticipate that transplantation of epithelial-specific stem/progenitor cells could be used in the future to improve the function of damaged lacrimal glands.
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