The eye is a complex organ composed of different primordial cell lineages. The retina, for example, develops from the neuroectoderm, the corneal epithelium and crystalline lens develop from the surface ectoderm, and the iris stroma and corneal endothelium and stroma develop from the neural crest. Recent studies with pluripotent stem cells, such as induced pluripotent stem (iPS) and embryonic stem (ES) cells, have revealed a wealth of information on retinal tissue regeneration and its mechanism of onset based on cellular self-organization, which led to the world's first iPS cell-derived retinal pigment epithelium graft in 2014. On the other hand, no method of inducing differentiation from pluripotent stem cells in the corneal epithelium of the anterior segment existed for a long time, and no isolation method had been established. We successfully induced colonies with a multi-band zone composed of various ocular cell lineages, including primordial corneal epithelial cell lineages derived from human iPS cells［self-formed ectodermal autonomous multi-zone (SEAM)]. In the various concentric zones induced in human iPS cell colonies, various primordial retinal, neural crest, crystalline lens, and ocular surface epithelial cells were methodically induced, with a pattern of development that strongly mimicked that of actual eye development. We also developed a method of selectively isolating only the cells committed to corneal epithelial cells based on the combinations of cell surface antigens and were successful in reconstructing highly pure and functional corneal epithelial tissues. Transplantation of the obtained iPS cell-derived corneal epithelial cell sheets into a rabbit model of corneal epithelial stem cell depletion allowed us to reconstruct the corneal epithelial layer and improve corneal barrier function.
Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc) 122: 841-850, 2018.