Current State and Future Perspectives in Corneal Endothelium Differentiation

Regenerative medicine in ocular diseases has shown major advances over the last few years. The most critical progress has been achieved for diseases of the cornea and retina, for which the transplantation of local and differentiated stem cells (SC) is being studied. The treatment of the cornea is aimed at restoring corneal clarity after severe injuries and diseases. Corneal blindness is the fourth leading cause of visual impairment worldwide, and access to corneal transplantation surgery, the main treatment for corneal blindness, is difficult given the shortage of tissue donors. For this reason, the development of alternative therapies using SC is of special interest. The corneal endothelium (CE) is the innermost layer of the cornea, and it is in contact with the aqueous humor. It consists of a monolayer of polygonal cells which maintains an optimal hydration state and clarity in the cornea through an active ATP-Na/K pump. This tissue possesses limited mitotic ability. Therefore, when major injury occurs, it can only be treated with a corneal graft. Recent advances have shown potential in harvesting corneal endothelial cells (CECs) in order to obtain enough quantities to perform a transplant. However, these strategies are still limited by the need for tissue donors, as well as by the long time lapses required to proliferate the CECs. SC isolated from different sources, including adipose tissue and dental pulp, are being investigated in regenerative medicine given their potential to differentiate into other cell lines. For use in CE restoration, a broad analysis must be performed, taking into account CE embryological pathways, current reports in SC differentiation into ocular tissues, and recently available bioinformatic tools, which can be used for differentiation assays. This review encompasses the present knowledge of CE development and embryological molecular signaling, recent reports in SC differentiation into CE, and the available bioinformatic tools used to direct in vitro SC differentiation.

Keywords: Bioinformatics, Bone marrow stem cell, Cornea, Corneal endothelium, Dental pulp stem cell, Differentiation, Embryogenesis, Embryonic stem cell, Growth factors, Induced pluripotent cells, Mesenchymal stem cell.