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G.V. Hegde, A.V. Das, I. Ahmad; Characterization of Retinal Stem Cell Niche . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3238.
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Purpose: Evidence is emerging that the maintenance of stem cells in terms of their self–renewal and state of commitment is closely regulated by their surrounding environment or their niche. The stem cell niche is defined by contributions from the surrounding cells, e.g., cells in different stages of development, endothelial and other supporting cells. Here, we present our initial attempt to characterize and define retinal stem cell niche. Methods: The cellular contributors to retinal stem cell niche may include, retinal cells in different developmental stages during retinal histogenesis and endothelial cells. We evaluated the influence of cultured endothelial cells and E3 (embryonic day 3) chick retinal cells on E14 rat retinal stem cells/progenitors on proliferation, self–renewal and differentiation. Dissociated E14 retinal cells were co–cultured with either endothelial cells or E3 chick retinal cells, and the number of BrdU positive cells/ clonal neurospheres/ differentiated cells were counted. To identify the specific signaling molecule in the niche, self–renewal/ differentiation was examined in the presence of antibodies to Shh and FGFRs. Results: In the presence of endothelial cells or endothelial cell–conditioned medium (CM), number of clonal neurospheres obtained from E14 retinal cells was significantly higher as compared to controls. The E3 chick retinal cells or E3 chick retinal cell CM influenced the differentiation of E14 retinal stem cells/progenitors; in the presence of E3 chick retinal cell CM, transcripts corresponding to regulators and markers of retinal ganglion cells, were decreased and increased when the function of FGFRs and Shh were blocked by antibodies, respectively. Conclusions: The factor(s) contributed to retinal stem cell niche by endothelial cells, promotes the proliferation and self–renewal of retinal stem cells/progenitors. The factor(s) contributed by the early retinal cells in the niche, in this particular experimental condition, influences the differentiation of retinal stem cells/progenitors, and it may include FGFs or/and Shh.
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