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

Research output: Contribution to journalArticle (Academic Journal)

236 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)741-747
Number of pages7
JournalNature Biotechnology
Volume31
Issue number8
DOIs
Publication statusPublished - 21 Jul 2013

Keywords

  • Animals
  • Blindness
  • Cell Culture Techniques
  • Cell Differentiation
  • Cell- and Tissue-Based Therapy
  • Embryonic Stem Cells
  • Green Fluorescent Proteins
  • Mice
  • Photoreceptor Cells
  • Photoreceptor Cells, Vertebrate
  • Retina
  • Rhodopsin
  • Stem Cell Transplantation

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  • Cite this

    Gonzalez-Cordero, A., West, E. L., Pearson, R. A., Duran, Y., Carvalho, L. S., Chu, C. J., Naeem, A., Blackford, S. J. I., Georgiadis, A., Lakowski, J., Hubank, M., Smith, A. J., Bainbridge, J. W. B., Sowden, J. C., & Ali, R. R. (2013). Photoreceptor precursors derived from three-dimensional embryonic stem cell cultures integrate and mature within adult degenerate retina. Nature Biotechnology, 31(8), 741-747. https://doi.org/10.1038/nbt.2643