Department of Stem Cells and Applied Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
Country
Japan
Year
2016
Journal
Nature
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 cells1–5.
Moreover, we and others have demonstrated the in vitro induction
of a corneal epithelial cell phenotype from pluripotent stem cells6–9.
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.