Effect of TGFβ1 and TGFβ1-inhibitor on Limbal Stem Cell Properties

Abstract

Corneal epithelium is constantly renewing itself from stem cells located at the limbus,
the transition zone between the corneal and neighboring conjunctival epithelium. The
maintenance of limbal stem cells (LSCs) is widely believed to be controlled by various cues
present in their niches. The aim of the present study was to investigate the effect of TGF-β, a
key cytokine found during corneal wound healing, on cultivated LSCs. We found that when
LSCs were grown at clonal density on 3T3 feeder, TGF-β1 treatment results in the clonal
transition from cobblestone-like colonies to spindle-shaped colonies with migrating
protrusions. Within spindle-shaped colonies there was marked reduction in putative stem cell
marker ΔNp63α expression. In contrast, treatment with SB431542, TGFβ-inhibitor, promotes
colony forming efficiency of LSCs as well as increase a proliferation rate of LSCs colonies.
Our results suggest that TGFβ signaling induces limbal epithelial stem cells to
transdifferentiate into fibroblast-like cells as described in epithelial-to-mesenchymal
transition (EMT). TGFβ-inhibitor may be useful in promoting corneal wound healing and
improve corneal transparency in patient with corneal injury.