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ES Micro-Environment Enhances Stemness and Inhibits Apoptosis in Human Limbal Stem Cells via the Maintenance of Telomerase Activity
Our previous work had found that telomerase rejuvenated in the cytoplasm of corneal epithelial cells cultured in embryonic stem cell-conditioned medium, the functional properties of stem-like corneal epithelial cells can be enhanced by co-culturing with embryonic stem cells (ESCs) via activation of...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3543452/ https://www.ncbi.nlm.nih.gov/pubmed/23326460 http://dx.doi.org/10.1371/journal.pone.0053576 |
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author | Liu, Zhiping Wan, Pengxia Duan, Hucheng Zhou, Jin Tan, Bowei Liu, Ying Zhou, Qiang Zhou, Chenjing Huang, Zheqian Tian, Bishan Li, Chaoyang Wang, Zhichong |
author_facet | Liu, Zhiping Wan, Pengxia Duan, Hucheng Zhou, Jin Tan, Bowei Liu, Ying Zhou, Qiang Zhou, Chenjing Huang, Zheqian Tian, Bishan Li, Chaoyang Wang, Zhichong |
author_sort | Liu, Zhiping |
collection | PubMed |
description | Our previous work had found that telomerase rejuvenated in the cytoplasm of corneal epithelial cells cultured in embryonic stem cell-conditioned medium, the functional properties of stem-like corneal epithelial cells can be enhanced by co-culturing with embryonic stem cells (ESCs) via activation of the integrinβ1-FAK-PI3K/Akt signaling pathway. The goal of this study was to explore the potential molecular mechanisms of the ES micro-environment that enhance the stem cell-like phenotype and inhibit apoptosis in human limbal stem cells (LSC). The LSC were cultured in different media, either CnT-20 medium or CnT-20 +20% ES culture supernatant (ESC-CM). We observed that LSC cultured in ESC-CM had an increased proliferative capacity, greater serial passage capacity, higher colony-forming efficiency (CFE) and higher levels of stem cell-associated marker than those cultured in CnT-20. Compared with CnT-20, ESC-CM enhanced the undifferentiated status and inhibited apoptosis in the LSC by promoting the maintenance of telomerase activity, which could reduce the generation of reactive oxygen species (ROS), maintain the membrane potential (Δψm) at higher levels and reduce the expression of the p21 protein. Our findings indicated that ESC-CM system induced LSC to maintain a stem cell phenotype and inhibit the process of apoptosis. These effects might partially be achieved via the telomerase-p21-mitochondrial axis and the activation of the FAK/Wnt signaling pathways. This study may have high impact and clinic implication on the expansion of LSC in regenerative medicine, especially for ocular surface reconstruction. |
format | Online Article Text |
id | pubmed-3543452 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35434522013-01-16 ES Micro-Environment Enhances Stemness and Inhibits Apoptosis in Human Limbal Stem Cells via the Maintenance of Telomerase Activity Liu, Zhiping Wan, Pengxia Duan, Hucheng Zhou, Jin Tan, Bowei Liu, Ying Zhou, Qiang Zhou, Chenjing Huang, Zheqian Tian, Bishan Li, Chaoyang Wang, Zhichong PLoS One Research Article Our previous work had found that telomerase rejuvenated in the cytoplasm of corneal epithelial cells cultured in embryonic stem cell-conditioned medium, the functional properties of stem-like corneal epithelial cells can be enhanced by co-culturing with embryonic stem cells (ESCs) via activation of the integrinβ1-FAK-PI3K/Akt signaling pathway. The goal of this study was to explore the potential molecular mechanisms of the ES micro-environment that enhance the stem cell-like phenotype and inhibit apoptosis in human limbal stem cells (LSC). The LSC were cultured in different media, either CnT-20 medium or CnT-20 +20% ES culture supernatant (ESC-CM). We observed that LSC cultured in ESC-CM had an increased proliferative capacity, greater serial passage capacity, higher colony-forming efficiency (CFE) and higher levels of stem cell-associated marker than those cultured in CnT-20. Compared with CnT-20, ESC-CM enhanced the undifferentiated status and inhibited apoptosis in the LSC by promoting the maintenance of telomerase activity, which could reduce the generation of reactive oxygen species (ROS), maintain the membrane potential (Δψm) at higher levels and reduce the expression of the p21 protein. Our findings indicated that ESC-CM system induced LSC to maintain a stem cell phenotype and inhibit the process of apoptosis. These effects might partially be achieved via the telomerase-p21-mitochondrial axis and the activation of the FAK/Wnt signaling pathways. This study may have high impact and clinic implication on the expansion of LSC in regenerative medicine, especially for ocular surface reconstruction. Public Library of Science 2013-01-11 /pmc/articles/PMC3543452/ /pubmed/23326460 http://dx.doi.org/10.1371/journal.pone.0053576 Text en © 2013 Liu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Liu, Zhiping Wan, Pengxia Duan, Hucheng Zhou, Jin Tan, Bowei Liu, Ying Zhou, Qiang Zhou, Chenjing Huang, Zheqian Tian, Bishan Li, Chaoyang Wang, Zhichong ES Micro-Environment Enhances Stemness and Inhibits Apoptosis in Human Limbal Stem Cells via the Maintenance of Telomerase Activity |
title | ES Micro-Environment Enhances Stemness and Inhibits Apoptosis in Human Limbal Stem Cells via the Maintenance of Telomerase Activity |
title_full | ES Micro-Environment Enhances Stemness and Inhibits Apoptosis in Human Limbal Stem Cells via the Maintenance of Telomerase Activity |
title_fullStr | ES Micro-Environment Enhances Stemness and Inhibits Apoptosis in Human Limbal Stem Cells via the Maintenance of Telomerase Activity |
title_full_unstemmed | ES Micro-Environment Enhances Stemness and Inhibits Apoptosis in Human Limbal Stem Cells via the Maintenance of Telomerase Activity |
title_short | ES Micro-Environment Enhances Stemness and Inhibits Apoptosis in Human Limbal Stem Cells via the Maintenance of Telomerase Activity |
title_sort | es micro-environment enhances stemness and inhibits apoptosis in human limbal stem cells via the maintenance of telomerase activity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3543452/ https://www.ncbi.nlm.nih.gov/pubmed/23326460 http://dx.doi.org/10.1371/journal.pone.0053576 |
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