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T. Zahir, E. Lavik, H. Klassen, R. Langer, M.J. Young; Differentiation of Retinal Progenitor Cells into Specific Cell Types . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1666.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To differentiate retinal progenitor cells (RPCs) into specific cell types (bipolar and photoreceptor cells) using exogenous factors, to enhance survival and integration of transplanted cells. Methods: The RPCs used in these studies were isolated from the neuroretina of postnatal day one GFP transgenic mice. They were then treated with several reagents including BDNF, CNTF, GDNF, KCl, retinoic acid, RPE cell conditioned medium, sodium butyrate, succinylated concanavalin A and taurine for up to two weeks. RPCs were also seeded onto biodegradable poly (lactic-co-glycolic acid) polymers and treated with CNTF for up to 14 days. These cells were then added to retinal explants from C3H (retinal degeneration) mice to determine if the cells would preferentially integrate into the inner nuclear layer and express the appropriate bipolar cell markers. Results: In vitro studies showed that CNTF (20ng/ml) treatment resulted in changes in cellular morphology and was able to increase the number of cells expressing bipolar markers (PKC and MGluR6). Retinoic acid (500 nM) and sodium butyrate (4 mM), in combination, induced changes in cellular morphology and the differentiated cells stained positive for photoreceptor marker (Recoverin), albeit with higher rates of cell death. Surviving RPCs differentiated into bipolar (>90%) and photoreceptor (>90%) cell types upon treatment with CNTF and retinoic acid and sodium butyrate in combination, respectively. In addition, the RPCs treated with CNTF prior to explantation, integrated into the inner nuclear layer and expressed bipolar cell markers. Conclusion: Exogenous treatments, and biodegradable polymer substrates offer great promise for manipulating the differentiation of stem cell populations prior to grafting. Future studies will combine these two approaches, with RPCs being seeded onto polymer substrates into which specific molecules have been incorporated. This will allow controlled release of the molecule, which may in turn induce differentiation and integration of RPCs.
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