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Photoreceptor precursors derived from three-dimensional embryonic stem cell cultures integrate and mature within adult degenerate retina
Anai Gonzalez-Cordero， Emma L West， Rachael A Pearson， Yanai Duran， Livia S Carvalho， Colin J Chu， Arifa Naeem， Samuel J I Blackford， Anastasios Georgiadis， Jorn Lakowski， Mike Hubank， Alexander J Smith， James W B Bainbridge， Jane C Sowden & Robin R Ali
Irreversible blindness caused by loss of photoreceptors may be amenable to cell therapy. We previously demonstrated retinal repair1 and restoration of vision through transplantation of photoreceptor precursors obtained from postnatal retinas into visually impaired adult mice2， 3. Considerable progress has been made in differentiating embryonic stem cells (ESCs) in vitro toward photoreceptor lineages4， 5， 6. However， the capability of ESC-derived photoreceptors to integrate after transplantation has not been demonstrated unequivocally. Here， to isolate photoreceptor precursors fit for transplantation， we adapted a recently reported three-dimensional (3D) differentiation protocol that generates neuroretina from mouse ESCs6. We show that rod precursors derived by this protocol and selected via a GFP reporter under the control of a Rhodopsin promoter integrate within degenerate retinas of adult mice and mature into outer segment–bearing photoreceptors. Notably， ESC-derived precursors at a developmental stage similar to postnatal days 4–8 integrate more efficiently compared with cells at other stages. This study shows conclusively that ESCs can provide a source of photoreceptors for retinal cell transplantation.
