Abstract
Purpose:
Limbal epithelial stem cell (LSC) transplantation is a prevalent therapeutic method for patients with LSC deficiency. The maintenance of stem cell characteristics in the process of culture expansion is critical for the success of ocular surface reconstruction. Ciliary neurotrophic factor (CNTF), a member of gp130 family, is an injury- and metabolic activity-induced up-regulation factor and has now been identified as an anti-injury factor and anti-obesity agent. Our study was to determine the effect of CNTF on LSC and cornea.
Methods:
The effects of CNTF on LSC and cornea were investigated using mouse corneal epithelial cells and streptozotocin-induced diabetic mice.
Results:
CNTF increased the numbers of holoclone in LSC monolayer culture and preserved the stemness of LSC in suspension culture by evidence of ΔNp63, Ki67, and ABCG2 expression. CFSE pulse-labeling assay also demonstrated that CNTF stimulated LSC proliferation. In air-lift culture of limbal equivalent, CNTF was capable of increasing the numbers of ΔNp63-positive cells. The mitogenic effect of CNTF was found to be mediated by the phosphorylations of Akt in LSC. In C57BL/6 and streptozotocin-induced diabetic mice subjecting to mechanical removal of cornea epithelium, CNTF facilitated corneal wound healing.
Conclusions:
In conclusion, the capability of expanding LSC in cell culture and in animal indicates the potential of CNTF in ameliorating limbal stem cell deficiency; and their uses as therapeutics for treating corneal wound.
Keywords: 482 cornea: epithelium •
721 stem cells