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Kohji Nishida; Challenges to the clinical application of iPSC- derived cornea. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2611.
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Presentation Description :
We have been challenging to develop iPS cell-based therapy for corneal epithelial diseases (limbal stem cell deficiency; LSCD) and corneal endothelial diseases (bullous keratopathy, Fuchs corneal endothelial dystrophy etc.). To do so, it is key to develop the robust standardized protocol on which corneal epithelial progenitor cells and corneal endothelial cells are induced from human iPS cells. In the past, there were no techniques to induce human iPS cells to differentiate into corneal epithelial and endothelial cells and to then isolate those cells to create functional corneal and epithelium and endothelium. We first succeeded in induction of corneal epithelium from human iPS cells. In fact, we developed a 2D culture system to promote cell-autonomous differentiation of human iPS cells. The culture system can use human iPS cells to generate a 2D structure we named (a self-formed ectodermal autonomous multi-zone (SEAM)) consisting of 4 concentric zones of cells. Major groups of cells that comprise the eye during development (e.g. corneal epithelium, the retina, and the epithelium of the lens) are produced at specific locations in the SEAM. The current study successfully isolated corneal epithelial progenitor cells from the 3rd zone of the SEAM, and successfully generated functional corneal epithelium. Corneal epithelium produced from human iPS cells was transplanted in an animal model, where that corneal epithelium was therapeutically effective. These results greatly help to start the first-in-human clinical trial of iPS cell-derived corneal epithelium for LSCD. We also generated functional corneal endothelium from human iPS cells using our SEAM method.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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