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Wnt activation as a potential therapeutic approach to treat partial limbal stem cell deficiency
Limbal epithelial stem/progenitor cells (LSCs) are adult stem cells located at the limbus, tightly regulated by their niche involving numerous signaling pathways, such as Wnt. Wnt proteins are secreted morphogens that play critical roles in embryonic development, stem cell proliferation, self-renewa...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10514048/ https://www.ncbi.nlm.nih.gov/pubmed/37735479 http://dx.doi.org/10.1038/s41598-023-42794-8 |
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author | Bonnet, Clémence González, Sheyla Deng, Sophie X. Zheng, Jie J. |
author_facet | Bonnet, Clémence González, Sheyla Deng, Sophie X. Zheng, Jie J. |
author_sort | Bonnet, Clémence |
collection | PubMed |
description | Limbal epithelial stem/progenitor cells (LSCs) are adult stem cells located at the limbus, tightly regulated by their niche involving numerous signaling pathways, such as Wnt. Wnt proteins are secreted morphogens that play critical roles in embryonic development, stem cell proliferation, self-renewal, tissue regeneration, and remodeling in adults. It has been shown that a small molecule Wnt mimic could improve LSCs expansion ex vivo. Damage to the LSCs and/or their niche can lead to limbal stem cell deficiency (LSCD), a condition that can cause corneal blindness and is difficult to treat. This study explored if repopulating residual LSCs in partial LSCD through Wnt activation could be a novel therapeutic approach. To mimic LSCD due to a chemical injury, single cultured LSCs were exposed to various concentrations of sodium hydroxide. A progressive loss of the LSCs phenotype was observed: the percentage of p63(bright) cells and cytokeratin (K)14(+) cells decreased while the percentage of K12(+) increased. Wnt activation was attained by treating the LSCs with lithium chloride (LiCl) and a small-molecule Wnt mimic, respectively. After 18 h of treatment, LSCs proliferation was increased, and the LSCs phenotype was recovered, while the untreated cells did not proliferate and lost their phenotype. The percentage of p63(bright) cells was significantly higher in the Wnt mimic-treated cells compared with untreated cells, while the percentage of K12(+) cells was significantly lower. These findings suggest that local Wnt activation may rescue LSCs upon alkaline injury. |
format | Online Article Text |
id | pubmed-10514048 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-105140482023-09-23 Wnt activation as a potential therapeutic approach to treat partial limbal stem cell deficiency Bonnet, Clémence González, Sheyla Deng, Sophie X. Zheng, Jie J. Sci Rep Article Limbal epithelial stem/progenitor cells (LSCs) are adult stem cells located at the limbus, tightly regulated by their niche involving numerous signaling pathways, such as Wnt. Wnt proteins are secreted morphogens that play critical roles in embryonic development, stem cell proliferation, self-renewal, tissue regeneration, and remodeling in adults. It has been shown that a small molecule Wnt mimic could improve LSCs expansion ex vivo. Damage to the LSCs and/or their niche can lead to limbal stem cell deficiency (LSCD), a condition that can cause corneal blindness and is difficult to treat. This study explored if repopulating residual LSCs in partial LSCD through Wnt activation could be a novel therapeutic approach. To mimic LSCD due to a chemical injury, single cultured LSCs were exposed to various concentrations of sodium hydroxide. A progressive loss of the LSCs phenotype was observed: the percentage of p63(bright) cells and cytokeratin (K)14(+) cells decreased while the percentage of K12(+) increased. Wnt activation was attained by treating the LSCs with lithium chloride (LiCl) and a small-molecule Wnt mimic, respectively. After 18 h of treatment, LSCs proliferation was increased, and the LSCs phenotype was recovered, while the untreated cells did not proliferate and lost their phenotype. The percentage of p63(bright) cells was significantly higher in the Wnt mimic-treated cells compared with untreated cells, while the percentage of K12(+) cells was significantly lower. These findings suggest that local Wnt activation may rescue LSCs upon alkaline injury. Nature Publishing Group UK 2023-09-21 /pmc/articles/PMC10514048/ /pubmed/37735479 http://dx.doi.org/10.1038/s41598-023-42794-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Bonnet, Clémence González, Sheyla Deng, Sophie X. Zheng, Jie J. Wnt activation as a potential therapeutic approach to treat partial limbal stem cell deficiency |
title | Wnt activation as a potential therapeutic approach to treat partial limbal stem cell deficiency |
title_full | Wnt activation as a potential therapeutic approach to treat partial limbal stem cell deficiency |
title_fullStr | Wnt activation as a potential therapeutic approach to treat partial limbal stem cell deficiency |
title_full_unstemmed | Wnt activation as a potential therapeutic approach to treat partial limbal stem cell deficiency |
title_short | Wnt activation as a potential therapeutic approach to treat partial limbal stem cell deficiency |
title_sort | wnt activation as a potential therapeutic approach to treat partial limbal stem cell deficiency |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10514048/ https://www.ncbi.nlm.nih.gov/pubmed/37735479 http://dx.doi.org/10.1038/s41598-023-42794-8 |
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