Corneal Stem Cell-Based Therapies

Abstract

Stem cell-based therapies for corneal diseases have been developing since the concept of limbal stem cells (LSCs) was established in 1986. LSCs reside in the limbal area, which is the conjunctional zone of cornea and conjunctiva. Loss of LSCs leads to limbal stem cell deficiency (LSCD), and corneal epithelial regeneration is severely impaired. One of the ways to overcome the LSCD is transplantation of LSCs or their substitute containing tissue. Here, we describe the details of six presently major cell-based therapies of LSCD, that is, conjunctival limbal autograft (CLAU), keratolimbal allograft (KLAL), living-related conjunctival limbal allograft (Lr-CLAL), cultivated limbal epithelial transplantation (CLET), simple limbal epithelial transplantation (SLET), and cultivated oral mucosal epithelial transplantation (COMET). As each method has its pros and cons, researchers are seeking other sources of stem cells especially for the treatment of bilateral LSCD. The cell sources currently being investigated can be categorized into four groups, (i) corneal epithelial cells induced from pluripotent stem cells, (ii) corneal epithelial cells induced from the other differentiated cell source (direct reprogramming), (iii) corneal epithelial alternatives from the other surface ectoderm-derived cells, and (iv) purified LSCs. Of these candidate cell sources, pluripotent stem cells such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and mesenchymal stem cells (MSCs) are increasingly being used for the induction of not only corneal epithelial cells but also keratocytes and corneal endothelial cells.