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Epigenetic Modification of the CCL5/CCR1/ERK Axis Enhances Glioma Targeting in Dedifferentiation-Reprogrammed BMSCs
The success of stem cell-mediated gene therapy in cancer treatment largely depends on the specific homing ability of stem cells. We have previously demonstrated that after in vitro induction of neuronal differentiation and dedifferentiation, bone marrow stromal cells (BMSCs) revert to a primitive st...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355636/ https://www.ncbi.nlm.nih.gov/pubmed/28216148 http://dx.doi.org/10.1016/j.stemcr.2017.01.016 |
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author | Chen, Rui Lee, Wayne Yuk-Wai Zhang, Xiao Hu Zhang, Jie Ting Lin, Sien Xu, Liang Liang Huang, Biao Yang, Fu Yuan Liu, Hai Long Wang, Bin Tsang, Lai Ling Willaime-Morawek, Sandrine Li, Gang Chan, Hsiao Chang Jiang, Xiaohua |
author_facet | Chen, Rui Lee, Wayne Yuk-Wai Zhang, Xiao Hu Zhang, Jie Ting Lin, Sien Xu, Liang Liang Huang, Biao Yang, Fu Yuan Liu, Hai Long Wang, Bin Tsang, Lai Ling Willaime-Morawek, Sandrine Li, Gang Chan, Hsiao Chang Jiang, Xiaohua |
author_sort | Chen, Rui |
collection | PubMed |
description | The success of stem cell-mediated gene therapy in cancer treatment largely depends on the specific homing ability of stem cells. We have previously demonstrated that after in vitro induction of neuronal differentiation and dedifferentiation, bone marrow stromal cells (BMSCs) revert to a primitive stem cell population (De-neu-BMSCs) distinct from naive BMSCs. We report here that De-neu-BMSCs express significantly higher levels of chemokines, and display enhanced homing abilities to glioma, the effect of which is mediated by the activated CCL5/CCR1/ERK axis. Intriguingly, we find that the activated chemokine axis in De-neu-BMSCs is epigenetically regulated by histone modifications. On the therapeutic front, we show that De-neu-BMSCs elicit stronger homing and glioma-killing effects together with cytosine deaminase/5-fluorocytosine compared with unmanipulated BMSCs in vivo. Altogether, the current study provides an insight into chemokine regulation in BMSCs, which may have more profound effects on BMSC function and their application in regenerative medicine and cancer targeting. |
format | Online Article Text |
id | pubmed-5355636 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-53556362017-03-24 Epigenetic Modification of the CCL5/CCR1/ERK Axis Enhances Glioma Targeting in Dedifferentiation-Reprogrammed BMSCs Chen, Rui Lee, Wayne Yuk-Wai Zhang, Xiao Hu Zhang, Jie Ting Lin, Sien Xu, Liang Liang Huang, Biao Yang, Fu Yuan Liu, Hai Long Wang, Bin Tsang, Lai Ling Willaime-Morawek, Sandrine Li, Gang Chan, Hsiao Chang Jiang, Xiaohua Stem Cell Reports Article The success of stem cell-mediated gene therapy in cancer treatment largely depends on the specific homing ability of stem cells. We have previously demonstrated that after in vitro induction of neuronal differentiation and dedifferentiation, bone marrow stromal cells (BMSCs) revert to a primitive stem cell population (De-neu-BMSCs) distinct from naive BMSCs. We report here that De-neu-BMSCs express significantly higher levels of chemokines, and display enhanced homing abilities to glioma, the effect of which is mediated by the activated CCL5/CCR1/ERK axis. Intriguingly, we find that the activated chemokine axis in De-neu-BMSCs is epigenetically regulated by histone modifications. On the therapeutic front, we show that De-neu-BMSCs elicit stronger homing and glioma-killing effects together with cytosine deaminase/5-fluorocytosine compared with unmanipulated BMSCs in vivo. Altogether, the current study provides an insight into chemokine regulation in BMSCs, which may have more profound effects on BMSC function and their application in regenerative medicine and cancer targeting. Elsevier 2017-02-16 /pmc/articles/PMC5355636/ /pubmed/28216148 http://dx.doi.org/10.1016/j.stemcr.2017.01.016 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Chen, Rui Lee, Wayne Yuk-Wai Zhang, Xiao Hu Zhang, Jie Ting Lin, Sien Xu, Liang Liang Huang, Biao Yang, Fu Yuan Liu, Hai Long Wang, Bin Tsang, Lai Ling Willaime-Morawek, Sandrine Li, Gang Chan, Hsiao Chang Jiang, Xiaohua Epigenetic Modification of the CCL5/CCR1/ERK Axis Enhances Glioma Targeting in Dedifferentiation-Reprogrammed BMSCs |
title | Epigenetic Modification of the CCL5/CCR1/ERK Axis Enhances Glioma Targeting in Dedifferentiation-Reprogrammed BMSCs |
title_full | Epigenetic Modification of the CCL5/CCR1/ERK Axis Enhances Glioma Targeting in Dedifferentiation-Reprogrammed BMSCs |
title_fullStr | Epigenetic Modification of the CCL5/CCR1/ERK Axis Enhances Glioma Targeting in Dedifferentiation-Reprogrammed BMSCs |
title_full_unstemmed | Epigenetic Modification of the CCL5/CCR1/ERK Axis Enhances Glioma Targeting in Dedifferentiation-Reprogrammed BMSCs |
title_short | Epigenetic Modification of the CCL5/CCR1/ERK Axis Enhances Glioma Targeting in Dedifferentiation-Reprogrammed BMSCs |
title_sort | epigenetic modification of the ccl5/ccr1/erk axis enhances glioma targeting in dedifferentiation-reprogrammed bmscs |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355636/ https://www.ncbi.nlm.nih.gov/pubmed/28216148 http://dx.doi.org/10.1016/j.stemcr.2017.01.016 |
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