Photoreceptor precursors derived from three-dimensional embryonic stem cell cultures integrate and mature within adult degenerate retina
Open Access
- 21 July 2013
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Biotechnology
- Vol. 31 (8), 741-747
- https://doi.org/10.1038/nbt.2643
Abstract
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 post-natal retinas into visually impaired adult mice2,3. Considerable progress has been made in differentiating embryonic stem cells (ESCs) in vitro toward photoreceptor lineages4-6. 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 Rhop.GFP-selected rod precursors derived by this protocol integrate within degenerate retinae 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 than cells at other stages. This study shows conclusively that ESCs can provide a source of photoreceptors for retinal cell transplantation.Keywords
This publication has 38 references indexed in Scilit:
- Defining the Integration Capacity of Embryonic Stem Cell-Derived Photoreceptor PrecursorsThe International Journal of Cell Cloning, 2012
- Self-Formation of Optic Cups and Storable Stratified Neural Retina from Human ESCsCell Stem Cell, 2012
- Effective Transplantation of Photoreceptor Precursor Cells Selected via Cell Surface Antigen ExpressionThe International Journal of Cell Cloning, 2011
- Optic Vesicle-like Structures Derived from Human Pluripotent Stem Cells Facilitate a Customized Approach to Retinal Disease TreatmentThe International Journal of Cell Cloning, 2011
- Self-organizing optic-cup morphogenesis in three-dimensional cultureNature, 2011
- Generation of retinal cells from mouse and human induced pluripotent stem cellsNeuroscience Letters, 2009
- Transplantation of Human Embryonic Stem Cell-Derived Photoreceptors Restores Some Visual Function in Crx-Deficient MiceCell Stem Cell, 2009
- Pharmacological disruption of the outer limiting membrane leads to increased retinal integration of transplanted photoreceptor precursorsExperimental Eye Research, 2008
- Toward the generation of rod and cone photoreceptors from mouse, monkey and human embryonic stem cellsNature Biotechnology, 2008
- Retinal repair by transplantation of photoreceptor precursorsNature, 2006