Human RPE Stem Cells Grown into Polarized RPE Monolayers on a Polyester Matrix Are Maintained after Grafting into Rabbit Subretinal Space

Transplantation 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. [Display omitted] •Adult hRPESC-derived RPE had comparable in vitro characteristics to fetal hRPE•hRPE monolayers survived 4 weeks on PET carriers under the rabbit retina•Better xenograft survival may be due to the maintained hRPE cell polarity•Atrophy of the retina overlaying the hRPE xenograft remains a future challenge Stanzel et al. have transplanted polarized monolayers of human retinal pigment epithelium (hRPE) grown on polyester membranes derived from adult hRPE stem cells or fetal tissue under the rabbit retina. The xeno-RPE survived 4 weeks with retained cell polarity characteristics in the subretinal space. These experiments support that adult hRPESC-derived RPE are a potential source for transplantation therapies.