title: Co-ordinated ocular development from human iPS cells and recovery of corneal function.
abstract: The eye is a complex organ with highly specialized constituent tissues derived from different primordial cell lineages. The retina, for example, develops from neuroectoderm via the optic vesicle, the corneal epithelium is descended from surface ectoderm, while the iris and collagen-rich stroma of the cornea have a neural crest origin. Recent work with pluripotent stem cells in culture has revealed a previously under-appreciated level of intrinsic cellular self-organization, with a focus on the retina and retinal cells. Moreover, we and others have demonstrated the in vitro induction of a corneal epithelial cell phenotype from pluripotent stem cells. These studies, however, have a single, tissue-specific focus and fail to reflect the complexity of whole eye development. Here we demonstrate the generation from human induced pluripotent stem cells of a self-formed ectodermal autonomous multi-zone (SEAM) of ocular cells. In some respects the concentric SEAM mimics whole-eye development because cell location within different zones is indicative of lineage, spanning the ocular surface ectoderm, lens, neuro-retina, and retinal pigment epithelium. It thus represents a promising resource for new and ongoing studies of ocular morphogenesis. The approach also has translational potential and to illustrate this we show that cells isolated from the ocular surface ectodermal zone of the SEAM can be sorted and expanded ex vivo to form a corneal epithelium that recovers function in an experimentally induced animal model of corneal blindness.
authors.affiliation: Department of Stem Cells and Applied Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.|Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Ryuhei
authors.initials: R
authors.lastname: Hayashi
authors.affiliation: Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ishikawa
authors.affiliation: Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Sasamoto
authors.affiliation: Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Katori
authors.affiliation: Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Nomura
authors.affiliation: Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ichikawa
authors.affiliation: Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Araki
authors.affiliation: Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Soma
authors.affiliation: Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kawasaki
authors.affiliation: Laboratory of Extracellular Matrix Biochemistry, Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Kiyotoshi
authors.initials: K
authors.lastname: Sekiguchi
authors.affiliation: Structural Biophysics Group, School of Optometry and Vision Sciences, College of Biomedical and Life Sciences, Cardiff University, Cardiff CF24 4HQ, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Quantock
authors.affiliation: Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Motokazu
authors.initials: M
authors.lastname: Tsujikawa
authors.affiliation: Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Nishida
mesh_terms: D000818:Animals; D019070:Cell Lineage; D003315:Cornea / Q000166:cytology* / Q000254:growth & development* / Q000502:physiology; D016039:Corneal Transplantation; D004475:Ectoderm / Q000166:cytology; D004847:Epithelial Cells / Q000166:cytology; D019573:Epithelium, Corneal / Q000166:cytology; D005260:Female; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D007908:Lens, Crystalline / Q000166:cytology; D051379:Mice; D009024:Morphogenesis; D010641:Phenotype; D011817:Rabbits; D020127:Recovery of Function; D055213:Retinal Pigment Epithelium / Q000166:cytology