title: Function of human pluripotent stem cell-derived photoreceptor progenitors in blind mice.
abstract: Photoreceptor degeneration due to retinitis pigmentosa (RP) is a primary cause of inherited retinal blindness. Photoreceptor cell-replacement may hold the potential for repair in a completely degenerate retina by reinstating light sensitive cells to form connections that relay information to downstream retinal layers. This study assessed the therapeutic potential of photoreceptor progenitors derived from human embryonic and induced pluripotent stem cells (ESCs and iPSCs) using a protocol that is suitable for future clinical trials. ESCs and iPSCs were cultured in four specific stages under defined conditions, resulting in generation of a near-homogeneous population of photoreceptor-like progenitors. Following transplantation into mice with end-stage retinal degeneration, these cells differentiated into photoreceptors and formed a cell layer connected with host retinal neurons. Visual function was partially restored in treated animals, as evidenced by two visual behavioral tests. Furthermore, the magnitude of functional improvement was positively correlated with the number of engrafted cells. Similar efficacy was observed using either ESCs or iPSCs as source material. These data validate the potential of human pluripotent stem cells for photoreceptor replacement therapies aimed at photoreceptor regeneration in retinal disease.
authors.affiliation: Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, England.
authors.forename: Alona O
authors.initials: AO
authors.lastname: Barnea-Cramer
authors.affiliation: Astellas Institute for Regenerative Medicine, 33 Locke Dr, Marlborough, MA 01752, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Astellas Institute for Regenerative Medicine, 33 Locke Dr, Marlborough, MA 01752, USA.
authors.forename: Shi-Jiang
authors.initials: SJ
authors.lastname: Lu
authors.affiliation: Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, England.|Moorfields Eye Hospital NHS Foundation Trust NIHR Biomedical Research Centre, London, England.
authors.forename: Mandeep S
authors.initials: MS
authors.lastname: Singh
authors.affiliation: Astellas Institute for Regenerative Medicine, 33 Locke Dr, Marlborough, MA 01752, USA.
authors.forename: Chenmei
authors.initials: C
authors.lastname: Luo
authors.affiliation: Astellas Institute for Regenerative Medicine, 33 Locke Dr, Marlborough, MA 01752, USA.
authors.forename: Hongguang
authors.initials: H
authors.lastname: Huo
authors.affiliation: Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, England.
authors.forename: Michelle E
authors.initials: ME
authors.lastname: McClements
authors.affiliation: Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, England.
authors.forename: Alun R
authors.initials: AR
authors.lastname: Barnard
authors.affiliation: Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, England.|Moorfields Eye Hospital NHS Foundation Trust NIHR Biomedical Research Centre, London, England.|Oxford University Hospitals NHS Trust Biomedical Research Centre, Oxford, England.
authors.forename: Robert E
authors.initials: RE
authors.lastname: MacLaren
authors.affiliation: Astellas Institute for Regenerative Medicine, 33 Locke Dr, Marlborough, MA 01752, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Lanza
mesh_terms: D000818:Animals; D001766:Blindness / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D002454:Cell Differentiation; D064593:Heterografts; D000066449:Human Embryonic Stem Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism / Q000473:pathology; D051379:Mice; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D012174:Retinitis Pigmentosa / Q000378:metabolism / Q000473:pathology / Q000628:therapy