Ex vivo cultured limbal stem/progenitor cells is an effective alternative to other surgical treatments for limbal stem cell deficiency, but a standard xenobiotic-free method for culturing the LSCs in vitro needs to be optimized. Because Wnt ligands are required for LSC expansion and preservation in vitro, to create a small-molecule Wnt mimic, we created a consolidated compound by linking a Wnt inhibitor that binds to the Wnt co-receptor Frizzled to a peptide derived from the N-terminal Dickkopf-1 that binds to Lrp (low-density lipoprotein receptor-related protein) 5/6, another Wnt co-receptor. This Wnt mimic not only enhances cellular Wnt signaling activation, but also improves the progenitor cell phenotype of in vitro cultured limbal epithelial cells. As the maintenance of stem cell characteristics in the process of culture expansion is essential for the success of ocular surface reconstruction, the small molecules generated in this study may be helpful in the development of pharmaceutical reagents for treating corneal wounds.

离体培养的角膜缘干细胞/祖细胞是治疗角膜缘干细胞缺陷的其他手术治疗的有效替代方法，但体外培养 LSC 的标准无外源方法需要优化。由于 LSC体外扩增和保存需要 Wnt 配体，为了创建小分子 Wnt 模拟物，我们通过将与 Wnt 共受体 Frizzled 结合的 Wnt 抑制剂与 N 末端衍生的肽连接起来，创建了一种巩固的化合物Dickkopf-1 与另一种 Wnt 共受体 Lrp（低密度脂蛋白受体相关蛋白）5/6 结合。这种Wnt模拟物不仅增强细胞Wnt信号激活，而且改善体外培养的角膜缘上皮细胞的祖细胞表型。由于培养扩增过程中干细胞特性的维持对于眼表重建的成功至关重要，因此本研究中产生的小分子可能有助于开发治疗角膜伤口的药物试剂。