Mesenchymal stem cells as an alternative source of stem cells for ocular surface regeneration

Purpose To test the therapeutic potential of mesenchymal stem cells (MSCs) to replace limbal stem cells (LSCs) for the reconstruction of the heavily damaged ocular surface in an experimental mouse model. Methods MSCs were isolated from the bone marrow of BALB/c mice and expanded in vitro. Their phenotypic markers, differentiation potential, immunoregulatory properties and ability to transdifferentiate into corneal epithelial cells were characterized. These in vitro expanded MSCs were transferred, using nanofiber scaffolds, onto the damaged ocular surface and their therapetic potential was evaluated. Results MSCs can be expanded in vitro and retain their differentiation potential. When they were cultured in the presence of an extract from a damaged cornea or in the supernatant from cultured corneal cells, MSCs expressed cytokeratin CK12, a marker of corneal epithelial cells. In addition, MSCs displayed strong immunosuppressive properties in vitro and in vivo. After their transfer onto the damaged ocular surface, they supported corneal epithelial healing and inhibited the local inflammatory reaction. The therapeutic potential of MSCs was proven by the rapid regeneration of the ocular surface in the presence of MSCs and by an attenuation of the expression of proinflammatory cytokine genes after the injury. Conclusion MSCs, which can be obtained relatively easily from bone marrow or adipose tissue, have the potential to replace LSCs for the reconstruction of the heavily damaged ocular surface.