ArticleInvestigative ophthalmology & visual science2019
Wnt Signaling Is Required for the Maintenance of Human Limbal Stem/Progenitor Cells In Vitro.
Article in Investigative ophthalmology & visual science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- Exosome-based therapies for corneal disorders: current status and future perspectives.MedScience · 2026Review
- Limbal Epithelial Stem Cells in Review: Immune and Lymphangiogenic Privilege and Their Clinical Relevance.Cells · 2026Review
- Review
- RSPO3 Promotes Proliferation and Self-Renewal of Limbal Epithelial Stem Cells Through a WNT/β-Catenin-Independent Signaling Pathway.Investigative ophthalmology & visual science · 2025Article
- Progress in Transdifferentiation of Autologous Alternative Cell Sources into Corneal Epithelial Cells.Stem cell reviews and reports · 2025Review
- Identification of XD23 as a potent inhibitor of osteosarcoma via downregulation of DKK1 and activation of the WNT/β-catenin pathway.iScience · 2024Article
- Targeting limbal epithelial stem cells: master conductors of corneal epithelial regeneration from the bench to multilevel theranostics.Journal of translational medicine · 2024Review
- Design principles and therapeutic applications of novel synthetic WNT signaling agonists.iScience · 2024Review
- Ocular Surface Regeneration by Limbal Stem Cells Therapies: State of the Art, Challenges, and Perspectives.Stem cells translational medicine · 2023Article
- WNT16b promotes the proliferation and self-renewal of human limbal epithelial stem/progenitor cells via activating the calcium/calcineurin A/NFATC2 pathway.Cell proliferation · 2023Article
- Wnt activation as a potential therapeutic approach to treat partial limbal stem cell deficiency.Scientific reports · 2023Article
- Review
- Wnt/β-Catenin Signaling Activation Induces Differentiation in Human Limbal Epithelial Stem Cells Cultured Ex Vivo.Biomedicines · 2023Article
- Review
- Axin2-lineage cells contribute to neonatal tendon regeneration.Connective tissue research · 2022Article
- Hsa-miR-143-3p inhibits Wnt-β-catenin and MAPK signaling in human corneal epithelial stem cells.Scientific reports · 2022Article
- R-etodolac is a more potent Wnt signaling inhibitor than enantiomer, S-etodolac.Biochemistry and biophysics reports · 2022Article
- WNT16B enhances the proliferation and self-renewal of limbal epithelial cells via CXCR4/MEK/ERK signaling.Stem cell reports · 2022Article
- Hsa-miR-150-5p inhibits Wnt-β-catenin signaling in human corneal epithelial stem cells.Molecular vision · 2022Article
- Commentary: Novel Cell Culture Paradigm Prolongs Mouse Corneal Epithelial Cell Proliferative ActivityFrontiers in cell and developmental biology · 2022Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Purpose: A chemical approach to examine the role of Wnt signaling in maintaining the stemness and/or proliferation of limbal stem/progenitor cells (LSCs). Methods: LSCs were isolated from human donor eyes and cultured as single cells for 12 to 14 days with the following small molecules: IIIC3, an antagonist of the Wnt signaling inhibitor Dickkopf (DKK), and IC15, a Wnt signaling inhibitor. Proliferation of LSCs in the presence of IIIC3 and IC15 was determined by the number of cells and colonies established. Maintenance of stemness was determined by p63α, cytokeratin (K)12, and K14 expression. Results: Activation of Wnt, through IIIC3-mediated DKK inhibition, resulted in similar colony forming efficiency (CFE) as in the untreated LSCs, but significantly increased the number of cultivated cells 7.21% with 5 μM. Inhibition of Wnt with IC15 significantly reduced the CFE (P ≤ 0.01) and the number of cultivated cells by 16% to 29%. Percentage of cells expressing high levels of p63α (p63αbright) and quantity of small cells (≤12 μm), which contain the LSCs, increased 4.71% and 11.26% (both P < 0.05), respectively, with 5 μM IIIC3. All concentrations of IIIC3 and IC15 retained the K14 undifferentiated marker (97%), while differentiation, as detected by expression of K12, was found in up to 2% of cells in 1 μM IIIC3, 1 μM IC15, or 5 μM IIIC3. Conclusions: Wnt signaling is required in LSC proliferation and maintenance of an undifferentiated state. The current study is a proof of concept that the Wnt pathway could be modulated in LSCs to enhance or decrease the efficiency of human LSC expansion.
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