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Nat Biotechnol. 2013 Aug;31(8):741-7. doi: 10.1038/nbt.2643. Epub 2013 Jul 21.

Photoreceptor precursors derived from three-dimensional embryonic stem cell cultures integrate and mature within adult degenerate retina.

Author information

1
Department of Genetics, UCL Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL UK.
2
Developmental Biology Unit, University College London, 30 Guilford Street, London, WC1N 1EH UK.
3
UCL Genomics, University College London, 30 Guilford Street, London, WC1N 1EH UK.
4
Molecular Immunology Unit, Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH UK.
#
Contributed equally

Abstract

Irreversible blindness caused by loss of photoreceptors may be amenable to cell therapy. We previously demonstrated retinal repair and restoration of vision through transplantation of photoreceptor precursors obtained from postnatal retinas into visually impaired adult mice. Considerable progress has been made in differentiating embryonic stem cells (ESCs) in vitro toward photoreceptor lineages. 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 ESCs. 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.

PMID:
23873086
PMCID:
PMC3826328
DOI:
10.1038/nbt.2643
[Indexed for MEDLINE]
Free PMC Article

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