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1.
Stem Cell Reports ; 9(1): 42-49, 2017 07 11.
Artículo en Inglés | MEDLINE | ID: mdl-28625537

RESUMEN

Age-related macular degeneration (AMD) is a common cause of central visual loss in the elderly. Retinal pigment epithelial (RPE) cell loss occurs early in the course of AMD and RPE cell transplantation holds promise to slow disease progression. We report that subretinal transplantation of RPE stem cell (RPESC)-derived RPE cells (RPESC-RPE) preserved vision in a rat model of RPE cell dysfunction. Importantly, the stage of differentiation that RPESC-RPE acquired prior to transplantation influenced the efficacy of vision rescue. Whereas cells at all stages of differentiation tested rescued photoreceptor layer morphology, an intermediate stage of RPESC-RPE differentiation obtained after 4 weeks of culture was more consistent at vision rescue than progeny that were differentiated for 2 weeks or 8 weeks of culture. Our results indicate that the developmental stage of RPESC-RPE significantly influences the efficacy of RPE cell replacement, which affects the therapeutic application of these cells for AMD.


Asunto(s)
Células Madre Adultas/citología , Diferenciación Celular , Degeneración Macular/terapia , Epitelio Pigmentado de la Retina/citología , Epitelio Pigmentado de la Retina/trasplante , Animales , Técnicas de Cultivo de Célula , Células Cultivadas , Humanos , Degeneración Macular/patología , Ratas , Epitelio Pigmentado de la Retina/patología , Porcinos , Visión Ocular
2.
J Ocul Pharmacol Ther ; 32(5): 304-9, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-27182605

RESUMEN

PURPOSE: Numerous preclinical studies have shown that transplantation of stem cell-derived retinal pigment epithelial cell (RPE) preserves photoreceptor cell anatomy in the dystrophic Royal College of Surgeons (RCS) rat. How rescue is spatially distributed over the eye, relative to the transplantation site, is less clear. To understand spatial variations in transplant efficacy, we have developed a method to measure the spatial distribution of rescued photoreceptor cells. METHODS: Human RPE Stem Cell-derived RPE (RPESC-RPE) cells were subretinally injected into RCS rat eyes. After tissue recovery and orientating the globe, a series of retinal sections were cut through the injected area. Sections were stained with DAPI (4',6-diamidino-2-phenylindole) and a number of photoreceptor nuclei were counted across the nasal-temporal and superior-inferior axes. These data were used to construct 2D maps of the area of photoreceptor cell saving. RESULTS: Photoreceptor cell preservation was detected in the injected temporal hemisphere and occupied areas greater than 4 mm(2) centered near the injection sites. Rescue was directed toward the central retina and superior and inferior poles, with maximal number of rescued photoreceptor cells proximal to the injection sites. CONCLUSIONS: RPESC-RPE transplantation preserves RCS photoreceptor cells. The photoreceptor cell contour maps readily convey the extent of rescue across the eye. The consistent alignment and quantification of results using this method allow the application of other downstream statistical analyses and comparisons to better understand transplantation therapy in the eye.


Asunto(s)
Células Fotorreceptoras de Vertebrados , Epitelio Pigmentado de la Retina/citología , Células Madre , Animales , Humanos , Ratas , Ratas Long-Evans , Ratas Mutantes
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