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Cell Journal، جلد ۱۷، شماره Suppl ۱، صفحات ۹-۱۰
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عنوان انگلیسی Is-3: RPE Replacement by Transplantation of Human Embryonic Stem Cell-Derived RPE in Rodent Models of Retinal Degeneration
چکیده انگلیسی مقاله Objective: Retinal diseases affecting the retinal pigment epithelium (RPE), like age-related macular degeneration, Stargardt disease or Leber’s congenital amaurosis, represent a leading cause for visual impairment and blindness with no cure currently established. Transplantation of RPE is discussed as a potential therapy for the replacement of degenerated RPE cells. Here we assessed the use of human embryonic stem cell- (hESC) derived RPE cells for transplantation into two rodent models of RPE dysfunction and loss. Materials and Methods: RPE cells were generated in vitro from hESCs and sub-retinally transplanted into Royal College of Surgeons (RCS) rats and wild-type mice systemically injected with sodium iodate. Sham- and fibroblast-injected animals served as controls. Experimental animals were analysed by immunohistochemistry, RT-PCR, electron-microscopy and thethickness of the outer nuclear layer was quantified. Results: RCS rats carry a spontaneous mutation in the Mertk gene leading to dysfunction of outer segment phagocytosis and photoreceptor degeneration. Following transplantation into RCS rats donor RPE cells mainly formed clusters in the subretinal space beside few small monolayer structures. Transplantation of hESC-derived RPE cells resulted in a significant thicker ONL in comparison to untreated or sham-injected hosts. However, transplanted fibroblasts showed a similar protective effect. Injection of sodium iodate caused complete RPE cell loss, photoreceptor degeneration, and altered gene and protein expression in outer and inner nuclear layers. Following transplantation, donor hESCderived RPE cells formed extensive monolayers that displayed wild-type RPE cell morphology, organization, and function, including phagocytosis of host photoreceptor outer segments. Conclusion: RPE cells derived from hESCs survive for considerable time periods within rodent models of retinal degeneration. Cluster formation and comparable rescue levels propagated by transplanted fibroblasts questions specific RPE function causative for the protective effects observed in RCS rats. Systemic injection of sodium iodate has considerable effects on RPE, photoreceptors, and inner nuclear layer neurons, and provides a model to assay reconstitution and maturation of RPE cell transplants.The availability of an RPEfree Bruch’s membrane in this model likely allows the unprecedented formation of extensive polarized cell monolayers from donor hESC-derived RPE cell suspensions.
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نویسندگان مقاله m carido | m carido


| k postel


| k postel


e تاناکا | e tanaka


m ader | m ader


نشانی اینترنتی http://celljournal.org/journal/article/abstract/27
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