Preclinical Study of Human Induced Pluripotent Stem Cell-derived Retinal Pigment Epithelium Cell Sheets Transplantation.

Age-related macular degeneration is one of the leading causes of blindness characterized by progressive dysfunction of retinal pigment epithelium (RPE) and RPE transplantation. The replacement of pathological RPE with healthy RPE, is being investigated for AMD treatment. In recent years increasing attention has been given to human induced pluripotent stem cells (hiPSCs) as a useful cell source for RPE transplantation. We generated hiPSC-derived RPE (hiPSC-RPE) cell sheets optimized to meet clinical use requiring efficacy, consistency, and safety. These grafts consist of a monolayer of cells without any artificial scaffolds, and express typical RPE markers, form tight junctions that exhibit polarized secretion of growth factors, and show phagocytotic ability and gene expression patterns similar to those of native RPE. Additionally, autologous non-human primate iPSC-RPE cell sheets showed no immune rejection or tumor formation. These results suggest that autologous hiPSC-RPE cell sheets may serve as a useful cell source for RPE transplantation.