Engineering of Human Corneal Endothelial Cells In Vitro

Abstract

Human corneal endothelial cells are responsible for controlling corneal transparency, however they are notorious for their limited proliferative capability. Thus, damage to these cells may cause irreversible blindness. Currently, the only way to cure blindness caused by corneal endothelial dysfunction is via corneal transplantation of a cadaver donor cornea with healthy corneal endothelium. Due to severe shortage of donor corneas worldwide, it has become paramount to develop human corneal endothelial grafts in vitro that can subsequently be transplanted in humans. Recently, we have reported effective expansion of human corneal endothelial cells by reprogramming the cells into progenitor status through use of p120-Kaiso siRNA knockdown. This new reprogramming approach circumvents the need of using induced pluripotent stem cells or embryonic stem cells. Successful promotion of this technology will encourage scientists to rethink how "contact inhibition" can safely be perturbed to our benefit, i.e., effective engineering of an in vivo-like tissue while successful maintaining the normal phenotype. In this review, we present current advances in reprogramming corneal endothelial cells in vitro, detail the methods to successful engineer human corneal endothelial grafts, and discuss their future clinical applications to cure corneal blindness.

Potential Factors of Corneal Endothelial Cells for Progression in Children with Uveitis

“…The cells have a Na + -K + ATP enzyme pump function [ 5 ] and constantly drain water molecules from the stroma into the anterior chamber, thereby maintaining a state of dehydration in the former and keeping the cornea transparent. Endothelial cells cannot be regenerated [ 6 ]. When the human corneal endothelium is damaged, healing occurs through the expansion of cells and their formation of a continuous layer on the inner surface of the cornea [ 7 ].…”

In vitro reconstructed 3D corneal tissue models for ocular toxicology and ophthalmic drug development

“…Also, functional corneal endothelial cells have been isolated from stromal mesenchymal and from pluripotent stem cells (Hatou et al 2013;McCabe et al 2015;Zhao and Afshari 2016). Methods of cultivation of HCEC cells and cell lines are advancing (Shima et al 2011;Palchesko et al 2015;Zhu et al 2019), and currently, there are a limited number of commercial sources of human endothelial cells; however, there is no accepted consensus on unique endothelial markers (Van den Bogerd et al 2019). HCEC cultures are not used in any validated test method, but endothelial cells are frequently included in the 3D corneal equivalents (Reichl 2008;Yamaguchi and Takezawa 2018).…”

Effects of Electromagnets on Bovine Corneal Endothelial Cells Treated with Dendrimer Functionalized Magnetic Nanoparticles

“…Recently, magnetic nanoparticle applications in ocular systems, such as corneal endothelial cell (CEC) migration and proliferation [ 16 , 17 ] under external magnetic forces, have received scholarly attention. In relevant studies, the CECs’ viability and morphology remained intact [ 16 , 18 ], and the cells’ metabolic activity was enhanced [ 19 , 20 ]. SPION-labeled CEC densities can be increased by using permanent magnets of different shapes and sizes.…”