Abstract

SummaryTransplantation of the retinal pigment epithelium (RPE) is being developed as a cell-replacement therapy for age-related macular degeneration. Human embryonic stem cell (hESC) and induced pluripotent stem cell (iPSC)-derived RPE are currently translating toward clinic. We introduce the adult human RPE stem cell (hRPESC) as an alternative RPE source. Polarized monolayers of adult hRPESC-derived RPE grown on polyester (PET) membranes had near-native characteristics. Trephined pieces of RPE monolayers on PET were transplanted subretinally in the rabbit, a large-eyed animal model. After 4 days, retinal edema was observed above the implant, detected by spectral domain optical coherence tomography (SD-OCT) and fundoscopy. At 1 week, retinal atrophy overlying the fetal or adult transplant was observed, remaining stable thereafter. Histology obtained 4 weeks after implantation confirmed a continuous polarized human RPE monolayer on PET. Taken together, the xeno-RPE survived with retained characteristics in the subretinal space. These experiments support that adult hRPESC-derived RPE are a potential source for transplantation therapies.

Highlights

  • The retinal pigment epithelium (RPE) is a cellular monolayer between the retina and the underlying choroidal vasculature

  • Human embryonic stem cell and induced pluripotent stem cell-derived RPE are currently translating toward clinic

  • We introduce the adult human RPE stem cell as an alternative RPE source

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Summary

Introduction

The retinal pigment epithelium (RPE) is a cellular monolayer between the retina and the underlying choroidal vasculature. RPE dysfunction significantly contributes to the pathophysiology of agerelated macular degeneration (AMD), a leading cause of blindness (Lim et al, 2012). Replacement of dysfunctional submacular RPE with a cell-based therapeutic agent represents a potentially curative treatment strategy (Binder et al, 2007). Some previous attempts in patients have been shown to improve vision, but most were limited by immune reactions, surgical complications, late-stage disease, or lack of an adequate RPE cell source (Stanzel and Holz, 2012). Translocation of an autologous patch of RPE/choroid remains clinically the most popular approach, because some patients benefit from the procedure, despite its high complication rates (van Zeeburg et al, 2012)

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