Therapy of corneal endothelial dysfunction with corneal endothelial cell-like cells derived from skin-derived precursors

Lin Shen,Liqun Du,Peng Sun,Le Yang,Canwei Zhang,Xinyi Wu

doi:10.1038/s41598-017-13787-1

Abstract

Corneal endothelial dysfunction occurs when corneal endothelial cells (CECs) are dramatically lost and eventually results in vision loss. Corneal transplantation is the only solution at present. However, corneal transplantation requires a fresh human cornea and there is a worldwide shortage of donors. Therefore, finding new functional CECs to replace human CECs is urgent. Skin-derived precursors (SKPs) can be easily acquired and have multiple differential potential. We co-cultured human SKPs with B4G12 cells in serum-free medium and obtained abundant CEC-like cells which had similar morphology and characteristic to human CECs. CEC-like cells exerted excellent therapeutic effect when they were transplanted into rabbit and monkey corneal endothelial dysfunction models by injection method. This protocol enables efficient production of CEC-like cells from SKPs. The renewable cell source, novel derivation method and simple treatment strategy may lead to potential applications in cell replacement therapy for corneal endothelial dysfunction.

Highlights

Corneal endothelial cells (CECs) are a monolayer of hexagonal cells covering the posterior surface of the cornea, and serve as a barrier between the corneal stroma and the aqueous humor
corneal endothelial cells (CECs) mainly originate from neural crest cells[11,12,13], so this tissue similarity, together with easy accessibility and low immunogenicity make Skin-derived precursors (SKPs) ideal seed cells be differentiated to CECs by mimicking the developmental process
Previous studies demonstrated that CECs-like cells can be induced from embryonic stem cells[18], adipose-derived stem cells[19], bone marrow-derived endothelial progenitor cells[20], neural crest cells[21], or corneal stroma stem cells[22] to treat corneal endothelial dysfunction

Summary

Introduction

Corneal endothelial cells (CECs) are a monolayer of hexagonal cells covering the posterior surface of the cornea, and serve as a barrier between the corneal stroma and the aqueous humor. SKPs can be isolated in large quantities from many parts of the skin in rodents and humans As they are multipotent, they can be differentiated into several functional cell types[8], and are able to suppress the allogeneic activation of T-lymphocytes resulting in an improved health status of animals suffering from a graft-versus-host reaction[9]. We injected CEC-like cells into rabbit and monkey corneal endothelial dysfunction models to test the CEC-like cell function in vivo. Results showed that CEC-like cells could be derived from SKPs, and they had similar morphology and characteristic to human CECs. Most importantly, our animal transplantation experiment was very successful that the corneal endothelial dysfunction models recovered in a very short time. Our therapeutic schedule may be a clinically relevant cell-based therapy for treating corneal endothelial dysfunction in the future

Methods

Results

Conclusion