摘要：SummaryEx vivocultured 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 LSCsin vitroneeds to be optimized. Because Wnt ligands are required for LSC expansion and preservationin 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 ofin vitrocultured 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.Graphical AbstractDisplay OmittedHighlights•MFH-ND is generated by linking a Frizzled inhibitor and an LRP5/6 inhibitor•MFH-ND activates the canonical Wnt pathway by oligomerizing Frizzled and LRP5/6•MFH-ND improves the stem cell phenotype of cultivated limbal epithelial cells•MFH-ND has therapeutic potential to improve limbal stem cell deficiency treatmentMolecular Biology; Stem Cells Research
