title: Photoreceptor precursors derived from three-dimensional embryonic stem cell cultures integrate and mature within adult degenerate retina.
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.
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL UK.
authors.forename: Anai
authors.initials: A
authors.lastname: Gonzalez-Cordero
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL UK.
authors.forename: Emma L
authors.initials: EL
authors.lastname: West
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL UK.
authors.forename: Rachael A
authors.initials: RA
authors.lastname: Pearson
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL UK.
authors.forename: Yanai
authors.initials: Y
authors.lastname: Duran
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL UK.
authors.forename: Livia S
authors.initials: LS
authors.lastname: Carvalho
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL UK.
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Chu
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL UK.
authors.forename: Arifa
authors.initials: A
authors.lastname: Naeem
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL UK.
authors.forename: Samuel J I
authors.initials: SJI
authors.lastname: Blackford
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL UK.
authors.forename: Anastasios
authors.initials: A
authors.lastname: Georgiadis
authors.affiliation: Developmental Biology Unit, University College London, 30 Guilford Street, London, WC1N 1EH UK.
authors.forename: Jorn
authors.initials: J
authors.lastname: Lakowski
authors.affiliation: UCL Genomics, University College London, 30 Guilford Street, London, WC1N 1EH UK.
authors.forename: Mike
authors.initials: M
authors.lastname: Hubank
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL UK.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Smith
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL UK.
authors.forename: James W B
authors.initials: JWB
authors.lastname: Bainbridge
authors.affiliation: Developmental Biology Unit, University College London, 30 Guilford Street, London, WC1N 1EH UK.
authors.forename: Jane C
authors.initials: JC
authors.lastname: Sowden
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL UK.|Molecular Immunology Unit, Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH UK.
authors.forename: Robin R
authors.initials: RR
authors.lastname: Ali
mesh_terms: D000818:Animals; D001766:Blindness / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D064987:Cell- and Tissue-Based Therapy; D053595:Embryonic Stem Cells / Q000166:cytology / Q000637:transplantation*; D049452:Green Fluorescent Proteins; D051379:Mice; D010786:Photoreceptor Cells; D020419:Photoreceptor Cells, Vertebrate; D012160:Retina / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D012243:Rhodopsin / Q000235:genetics / Q000378:metabolism; D033581:Stem Cell Transplantation
chemical_list: D049452:Green Fluorescent Proteins; D012243:Rhodopsin