Extensive monolayer formation after transplantation depends on an RPE subpopulation derived from human iPSCs

Abstract

Summary Loss of retinal pigment epithelium (RPE) in the eye leads to photoreceptor dysfunction, death, and eventually, vision loss. Cell replacement strategies using RPE cells derived in vitro from pluripotent stem cells are currently evaluated as a potential therapeutic strategy. Generation of polarized monolayers represents an essential prerequisite for proper RPE function; however, monolayer formation following transplantation of RPE suspensions has not been systematically assessed. Using the sodium iodate mouse model of acute RPE depletion, significant increase in monolayer formation capacity of passage 1 vs. 2 human induced pluripotent stem cell (iPSC)-derived RPE cells was observed three weeks post-transplantation. Transplant-derived monolayers showed characteristic apicobasal polarity, RPE marker expression, phagocytosis function, and preservation of the host outer nuclear layer. The cell surface marker panel CD54+/PSA-NCAM− was identified to enrich for an RPE subpopulation with a high potential for monolayer formation following transplantation. Results underline the importance of defining and isolating competent cell subpopulations for successful RPE transplantation.