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E.B. Lavik, H. Klassen, K. Warfvinge, E. Scherfig, J.F. Kiilgaard, J.U. Proust, R.S. Langer, M.J. Young; Polymer Scaffolds Provide Support and Guidance for Retinal Stem Cells in Retinal Degeneration Models . Invest. Ophthalmol. Vis. Sci. 2003;44(13):508.
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Purpose: Retinal stem cells (RSCs) show great promise in studies of retinal development, and may someday be used to treat retinal degeneration. RSCs are self-renewing cells capable of differentiating into the different retinal cell types, including photoreceptors. We hypothesized that a biodegradable polymer scaffold could deliver these cells to the subretinal space in a more organized manner than bolus injections, while also providing the graft with laminar organization and structural guidance channels. Methods: Highly porous scaffolds were fabricated from blends of poly(L-lactic acid) and poly(lactic-co-glycolic acid) using a freeze-drying technique which produces pores oriented normal to the plane of the scaffold. RSCs (originally isolated from neonatal GFP-transgenic mice) were seeded on the polymers and cultured for 14 days. Seeded scaffolds were then either co-cultured with degenerating mouse retinas or transplanted to the healthy or injured retinas of juvenile pigs. Results: Co-culture of the seeded scaffolds with explanted degenerating retina was associated with substantial migration of RSCs from the scaffold into the explant. Remaining RSCs maintained a radial orientation within the polymer, in some cases exhibiting morphologies suggestive of photoreceptors and expressing photoreceptor markers. Such morphologies have not been seen in culture without polymer substrates. Mouse RSCs transplanted to the porcine model survived, oriented and remained within the polymer scaffolds for 14 days. However, no transplanted cells were found integrating in the retina, and in HE-sections a giant cell reaction was observed. Pore size increased over this period, a sign the scaffolds were degrading. Conclusions: Degradable polymer scaffolds provide support and laminar organization for grafted RSCs, as well as physical guidance to the cells. Donor cell morphology appears to benefit from this strategy, particularly in culture. Scaffold substrates provide a useful tool for delivery of stem cells to the retina as part of a tissue engineering strategy.
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