iPS cells ‐ an alternative source of RPE?

Purpose We have previously shown that human embryonic stem cells spontaneously differentiate into RPE, and, after transplantation into the dystrophic RCS rat, maintain visual acuity. Recent advances in the generation of stem cells from somatic cells have led us to investigate the use of induced pluripotent stem cells (iPS) as a potential source of therapeutic RPE. Methods iPS cells spontaneously differentiate after removal of bFGF from the culture medium. Isolated pigmented colonies were dissociated for expansion. The enriched population was then characterised morphologically and at the gene and protein expression level. Functionality of iPS‐derived RPE cells was assessed by RPE phagocytosis of retinal debris in vitro and in vivo. The therapeutic effect of iPS‐derived RPE was examined by injection of cells into the subretinal space of the dystrophic RCS rat. Results In culture iPS‐RPE were morphologically similar to, and expressed many markers of developing and mature RPE. These cells also phagocytose photoreceptor material, in vitro and in vivo following transplantation into the RCS dystrophic rat. Preservation of the neural retina layers and maintenance of visual acuity was observed 13 weeks following transplantation, however at this stage very few human cells remained and a number of large pigmented macrophages were observed in the subretinal space. Conclusion iPS cells can readily differentiate into functional RPE which facilitate the short‐term maintenance of photoreceptors. However, long‐term maintenance of the dystrophic RCS rat neural retina is likely to be due to a protective host response initiated against the xenografted cells. The use of iPS‐RPE as a cell therapy requires further investigation, however these cells provide a new model system in which to study RPE specific diseases in vitro.