Abstract

SummaryHere, we evaluate the efficacy of cryopreserved human embryonic stem cell (hESC)-derived corneal endothelial cells (CECs) to form a functional monolayer of corneal endothelium (CE) in rabbits and monkeys. We injected cryopreserved hESC-derived CECs into the anterior chamber of rabbits and monkeys either immediately after mechanical scraping of the central CE or a few days later when corneal edema developed. All preclinical models developed deturgesced and clear corneas following the injection of cryopreserved hESC-derived CECs and remained comparable to the corneas of the untreated eye. Confocal scanning microscopy confirmed an intact structure of hexagonal/polygonal cells and immunohistochemical analysis illustrated a monolayer expressing barrier and pump function proteins in the regenerated CE. The necropsy examination confirmed no remarkable change in multiple tissues assessed for teratoma formation. In conclusion, our data demonstrate the efficacy of cryopreserved hESC-derived CECs to form a functional CE on the denuded Descemet's membrane.

Highlights

  • The corneal endothelium (CE) is the innermost monolayer of the cornea and is composed of hexagonal/polygonal cells that maintain corneal transparency by mediating hydration through the barrier and pump functions (Bonanno, 2012)

  • We previously reported the differentiation of peripheral blood mononuclear cell (PBMC)-originated, induced pluripotent stem cells (iPSCs) to corneal endothelial cells (CECs) that share a similar proteome profile with human CE (Ali et al, 2018a)

  • The examination of human embryonic stem cell (hESC)-derived CECs for expression of zona-occludens-1 (ZO-1) by immunostaining illustrated expression of ZO-1 at cell boundaries (Figures 1A–1C) and confirmed the tightly packed layer of hESC-derived CECs generated under xeno-free conditions

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Summary

Introduction

The corneal endothelium (CE) is the innermost monolayer of the cornea and is composed of hexagonal/polygonal cells that maintain corneal transparency by mediating hydration through the barrier and pump functions (Bonanno, 2012). The only treatment modality to restore corneal endothelial dysfunction mediated vision loss is human donor tissue–dependent surgical transplantation, whereas full and partial-thickness keratoplasty techniques have been effective in restoring vision in patients affected with corneal endothelial dystrophies. In many areas of the world, transplantable-grade donor CE is limited. A global survey of corneal transplant surgery reported a considerable shortage of corneal transplant tissue, with only one cornea available for every 70 patients in need (Gain et al, 2016). CEC injection has received recent attention to address the worldwide shortage of transplantable-grade donor CE. Kinoshita and colleagues have reported the successful treatment of 11 patients suffering from bullous keratopathy and

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