Cell therapy with human induced pluripotent stem cell-derived retinal pigment epithelium and retinal precursor cells prevents visual function loss in a rat model of retinal degeneration

Abstract Photoreceptor loss is the principal cause of blindness in retinal degenerative diseases (RDD). Whereas some therapies exist for early stages of RDDs, no effective treatment is currently available for later stages, and once photoreceptors are lost the only option to rescue vision is cell transplantation. Using the RCS rat model of retinal degeneration, we sought to determine whether combined transplantation of human induced pluripotent stem cell (hiPSC)-derived retinal precursor cells (RPC) and retinal pigment epithelial (RPE) cells was superior to RPE or RPC transplantation alone in preserving retinal from degeneration. hiPSC-derived RPC and RPE cells expressing GFP were transplanted into the subretinal space of rats. In vivo monitoring showed that grafted cells survived 12 weeks in the subretinal space and rats treated with RPE+RPC therapy exhibited better conservation of the outer nuclear layer and visual response than RPE-treated or RPC-treated rats. Transplanted RPE cells integrated in the host RPE layer whereas RPC mostly remained in the subretinal space, although a limited number of cells integrated in the ONL. In conclusion, the combined transplantation of hiPSC-derived RPE and RPC is a potentially superior therapeutic approach to protect retina from degeneration in RDDs.