Purchase this article with an account.
Kohji Nishida; Development of stem cell-based therapy for cornea -from tissue stem cell to iPS cell. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4771.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Presentation Description :
Complete loss of corneal epithelial stem cells because of severe eye disease leads to limbal stem-cell deficiency (LSCD) with corneal vascularization and opacification with severe visual loss. We previously developed a unique method with tissue-engineered epithelial cell sheets using the patient’s autologous corneal or oral mucosal stem cells. Ocular surface reconstruction using autologous epithelial cell sheets containing stem cells has drastically changed the treatment of LSCD because it can prevent potential problems associated with limbal transplantation, including immune rejection and donor tissue shortages. Although the effectiveness and safety of this surgical approach have been confirmed to some extent by our past clinical research, efforts to make its use more widespread are required; the clinical trials using GMP-grade products are now on going.More recently, we have been developing a stem cell-based therapy using autologous oral mucoal epithelium. More recently, we also have been challenging to develop iPS cell-based therapy. In the past, there were no techniques to induce human iPS cells to differentiate into corneal epithelial cells and to then isolate those cells to create functional corneal epithelium. 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 developed in this study can use human iPS cells to generate a 2-dimensional structure (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 this study also 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.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
This PDF is available to Subscribers Only