| The retinal pigmented epithelium (RPE) is a monolayer of cells found at the back of the retina in direct contact with the rod and cone photoreceptors. The RPE serves many roles in the maintenance of visual function including retinoid metabolism, secretion of trophic factors, and phagocytosis of photoreceptor outer segments. Dysfunction or death of the RPE in diseases such as age-related macular degeneration, retinitis pigmentosa and Stargardt macular dystrophy is implicated in vision loss. While current therapies for these diseases are limited, transplantation of new RPE is a promising option. Human embryonic (hESC) and induced pluripotent (iPSC) stem cells can potentially provide unlimited sources of RPE for transplantation. We have derived RPE from spontaneously differentiating hESC.s and iPSC.s and shown similar gene expression, protein expression and phagocytosis function in comparison to cultured fetal human RPE. Transplantation of stem cell-RPE into a rat model of retinal degeneration shows rescue of visual function. These initial studies show that stem cell-derived RPE is a good candidate for use in cellular therapy.;To improve upon the spontaneous and undefined nature of RPE development from stem cells, we have studied the differentiation process from pluripotency to mature RPE, resulting in three important findings. First, stages of differentiation can be tracked by microRNA expression, which can also be used to define two distinct pluripotent states of undifferentiated stem cells. Second, RPE can be derived in a defined, manner more suitable for translation to human clinical trials. Third, differentiation of hESC.s can be quickly and efficiently directed to RPE through the addition of exogenous growth factors and small molecules.;These studies show that RPE can be efficiently derived from pluripotent stem cells in a defined manner. The resulting RPE are highly similar to primary cultures of RPE and can rescue visual function in an animal model. These attributes make stem cell-RPE a potentially useful source of cells for the treatment of degenerative eye diseases. |
