Review: corneal endothelial cell derivation methods from ES/iPS cells

Abstract

Globally, approximately 12.7 million people are awaiting a transplantation, while only 185,000 cases of corneal transplantation are performed in a year. Corneal endothelial dysfunction (bullous keratopathy) due to Fuchs’ corneal endothelial dystrophy, or insults associated with intraocular surgeries, shared half of all indications for corneal transplantation. Regenerative therapy for corneal endothelium independent of eye bank eyes has great importance to solve the large supply-demand mismatching in corneal transplantation and reduce the number of worldwide corneal blindness. If corneal endothelial cells could be derived from ES or iPS cells, these stem cells would be the ideal cell source for cell therapy treatment of bullous keratopathy. Four representative corneal endothelial cell derivation methods were reviewed. Components in earlier methods included lens epithelial cell-conditioned medium or fetal bovine serum, but the methods have been improved and materials have been chemically more defined over the years. Conditioned medium or serum is replaced to recombinant proteins and small molecule compounds. These improvements enabled to open the corneal endothelial developmental mechanisms, in which epithelial-mesenchymal and mesenchymal-endothelial transition by TGF beta, BMP, and Wnt signaling have important roles. The protocols are gradually approaching clinical application; however, proof of efficacy and safety of the cells by adequate animal models are the challenges for the future.

Transcriptome dataset of human corneal endothelium based on ribosomal RNA-depleted RNA-Seq data

“…Indeed, a clinical trial involving injection of cultured corneal endothelial cells into the anterior chamber of the eye has been initiated in Japan 8 . The induction of corneal endothelial cells from human pluripotent stem cells (iPSCs) has been reported, and the transplantation of those cells has been proposed as a potential decompensation therapy 9 . Along this line, many researchers have devoted their efforts to determining selective markers for the corneal endothelium to validate cultured cells for clinical use [10][11][12][13][14][15] .…”

State-of-the-Art Technology of Model Organisms for Current Human Medicine

“…Since the discovery of transcription factor-induced pluripotent stem (iPS) technology [14,15], regenerative medicine for corneal endothelial cells [16], cardiocytes [17], hepatocytes [18], and drug screening has been established [19]. Remarkably, the present in vitro technology can increase cell sheets or partial tissues, which are far from organs with complex structures formed after natural development and are not induced by embryonal stem (ES) cells in vivo.…”

A new alternative for corneal endothelial regeneration using autologous dental pulp stem cells

“…Corneal transplantation, known as keratoplasty, is the most frequently performed type of transplant worldwide, with over 185,000 procedures performed each year [1]. The main indication of corneal transplantation in the US is Fuchs dystrophy, a disease related to the innermost corneal layer, known as corneal endothelium [2].…”

“…In fact, endothelial keratoplasties, where only the corneal endothelium is replaced, represent 60% of all corneal transplants, and this percentage is increasing every year [3]. The lack of donors, together with an increased demand for corneal tissue due to population aging, urges to nd alternative solutions [1]. In this context, cell-based therapies are being developed in order to overcome actual limitations [1].…”

“…The lack of donors, together with an increased demand for corneal tissue due to population aging, urges to nd alternative solutions [1]. In this context, cell-based therapies are being developed in order to overcome actual limitations [1].…”