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M. Tomita, E. Lavik, H. Klassen, T. Zahir, R. Langer, M.J. Young; Enhanced Survival and Differentiation Into Photoreceptor in Retinal Progenitor Cells Transplantation Using Polymer Composite Graft . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3227.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Mammalian retinal progenitor cells (RPCs) can be isolated and expanded in culture, and differentiate into retinal neurons upon grafting to the eye. However, cell delivery and survival remain formidable obstacles to clinical application of RPCs. In order to overcome this hurdle, we studied whether the use of polymer composite grafts result in increased cell survival and differentiation into photoreceptor cells when placed in the subretinal space, compared to conventional injections. Methods: The biodegradable polymer (PLA/PLGA) coated with laminin was cultured with RPCs isolated from EGFP mice. One week after culture, composites were cut into 0.3 x 0.5 mm pieces. Every other piece was sectioned to assess total cell number before transplantation. Alternate pieces were transplanted into the subretinal space of C57BL/6 and rho–/– mice (n=57). A single cell suspension, containing the same number of RPCs, was also transplanted as a control. Eyes were enucleated and sectioned at day 0, 1 week, 2 weeks, and 4 weeks. Samples were stained with DAPI, and cell survival was assessed. The sections were also stained for markers of mature retinal neurons and astrocytes. Results: Composite grafts result in at least a 10–fold increase in surviving cells at 4 weeks, with a 16–fold increase in cell delivery, compared to conventional transplantation. Grafted RPCs migrated into host retina, and expressed NF200, GFAP, PKC–alpha, recoverin, and rhodopsin. Only cells grafted on the polymer substrate expressed rhodopsin in rho –/– mice. Conclusions: Biodegradable polymer/progenitor cell composite grafts provide an effective means of increasing progenitor cell survival and differentiation into photoreceptor when transplanted to the subretinal space.
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