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Co-ordinated ocular development from human iPS cells and recovery of corneal function

Hayashi, Ryuhei, Ishikawa, Yuki, Sasamoto, Yuzuru, Katori, Ryosuke, Nomura, Naoki, Ichikawa, Tatsuya, Araki, Saori, Soma, Takeshi, Kawasaki, Satoshi, Sekiguchi, Kiyotoshi, Quantock, Andrew J, Tsujikawa, Motokazu and Nishida, Kohji 2016. Co-ordinated ocular development from human iPS cells and recovery of corneal function. Nature 531 (7594) , pp. 376-380. 10.1038/nature17000

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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 cells1,2,3,4,5. Moreover, we and others have demonstrated the in vitro induction of a corneal epithelial cell phenotype from pluripotent stem cells6,7,8,9. 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Optometry and Vision Sciences
Publisher: Nature Publishing Group
ISSN: 0028-0836
Date of Acceptance: 14 January 2016
Last Modified: 17 Feb 2020 10:30
URI: http://orca.cf.ac.uk/id/eprint/101921

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