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Shigeto Shimmura; Regeneration of the corneal endothelium from iPSC. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© ARVO (1962-2015); The Authors (2016-present)
Presentation Description :
The cornea consists of the epithelium, stroma and endothelium, all of which contain unique cells that are vital for the homeostasis of the cornea. Stem cells for generating all 3 layers of the cornea have been reported both in mice and humans, and studies to apply these cells to the clinic are underway. Since Yamanaka et. al. successfully developed induced pluripotent stem (iPS) cells from somatic cells by forced reprogramming using the transcriptional factors OCT4, SOX2, c-MYC, and KLF4, these pluripotent stem cells have become the focus of intense study. Clinical application of stem cells in the treatment of corneal disease will probably involve both somatic stem cells and iPS cells depending on the disease.The corneal endothelium is an ideal tissue for iPSC application due to the following reasons:1) Immuno-priveledged properties of the anterior chamber.2) Small number of required cells.3) Transparency of the cornea that will allow observation of the cells following transplantation.Corneal endothelial-like cells from iPSC is possible using inducing culture medium containing factors such as retinoic acid and GSK-3b inhibitors. Cells with neural crest properties can be observed as CD271/ CD49d double-positive cells by flow cytometry. Sphere culture of induced endothelial cells further allows the formation of tight junctions, with enhanced expression of N-cadherin and Na,K-ATPase. Preliminary in vivo data in rabbits show that these cells for a monolayer, and can rescue the cornea from edema due to cell loss. Further refinements are underway prior to clinical trials.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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