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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2017
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.
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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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