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Comparison of the proliferation and differentiation ability between adult rat retinal stem cells and cerebral cortex-derived neural stem cells.

Liu IH, Chen SJ, Ku HH, Kao CL, Tsai FT, Hsu WM, Lo CW, Kuo YH, Kuo CD, Lee CH, Chiou SH

Department of Ophthalmology, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan, ROC.

Recent studies have demonstrated that retinal stem cells (RSCs) and stem cells of the central nervous system both exhibited the abilities of self-renewal, proliferation and differentiation into multilineage. In the present study, we compared the proliferation and differentiation abilities between RSCs and cerebral corticex-derived neural stem cells (CNSCs) of adult rats. Stem cells isolated from pigmented ciliary margins of eyes and cerebral cortical tissues of adult rats were cultured in 96-well plates that contained serum-free medium with epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). In contrast to RSCs, which stopped proliferating after the 8th week, the total cell count of neurospheres in CNSCs increased twofold at the 5th week and more than fourfold at the 10th week after in vitro culture. In contrast, RSCs stopped proliferating after 8 weeks of culture. After adding 2% fetal calf serum and withdrawing EGF and bFGF from the culture medium, the percentages of nestin-positive cells(20.6 +/- 2.7%), microtubule-associated-protein-2-positive neurons (33.2 +/- 3.9%) and glial-fibrillary-acidic-protein-positive glial cells(51.3 +/- 6.2%) in the differentiated CNSCs were significantly higher than those in the differentiated RSCs (10.2 +/- 1.9, 22.3 +/- 1.3 and 44.6 +/- 5.1%, respectively; p < 0.05). We also found that the combination of transforming growth factor beta type III with retinoic acid played an important role in the induction of CNSCs to differentiate into opsin-positive cells. Our data demonstrated that CNSCs displayed a higher ability of proliferation and retinal lineage. This report also offers an alternative protocol of cell reproduction for producing retinal cells.

Published 10 June 2005 in Ophthalmologica, 219(3): 171-6.
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