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Epigenetic modification of the CCL5/CCR1/ERK axis enhances glioma targeting in dedifferentiation-reprogrammed BMSCs

Epigenetic modification of the CCL5/CCR1/ERK axis enhances glioma targeting in dedifferentiation-reprogrammed BMSCs
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 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.

Journal Article
2213-6711
Chen, Rui
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Lee, Wayne Yuk-Wai
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Zhang, Xiao Hu
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Zhang, Jie Ting
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Lin, Sien
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Xu, Liang Liang
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Huang, Biao
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Yang, Fu Yuan
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Liu, Hai Long
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Wang, Bin
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Tsang, Lai Ling
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Willaime-Morawek, Sandrine
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Li, Gang
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Chan, Hsiao Chang
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Jiang, Xiaohua
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Chen, Rui
941fa635-535a-425b-86bb-3ef9476bb571
Lee, Wayne Yuk-Wai
4787aa7f-c131-406d-81d3-676abbf65d17
Zhang, Xiao Hu
a621e381-98d8-49bc-9fdb-700734ac5773
Zhang, Jie Ting
8499c002-e67a-4ee6-a8f7-e943159ac1b0
Lin, Sien
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Xu, Liang Liang
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Huang, Biao
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Yang, Fu Yuan
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Liu, Hai Long
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Wang, Bin
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Tsang, Lai Ling
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Willaime-Morawek, Sandrine
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Li, Gang
236aa0b3-e251-45a6-9adf-3ac5b7d174c8
Chan, Hsiao Chang
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Jiang, Xiaohua
58839217-38ee-45c3-b653-3b6aa7216f13

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 and Jiang, Xiaohua (2017) Epigenetic modification of the CCL5/CCR1/ERK axis enhances glioma targeting in dedifferentiation-reprogrammed BMSCs. Stem Cell Reports, 8. (doi:10.1016/j.stemcr.2017.01.016).

Record type: Article

Abstract

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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More information

Accepted/In Press date: 16 January 2017
e-pub ahead of print date: 16 February 2017
Published date: 14 March 2017
Additional Information: Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Keywords: Journal Article
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 406163
URI: https://eprints.soton.ac.uk/id/eprint/406163
ISSN: 2213-6711
PURE UUID: 549dd2cd-d0f7-44b0-a802-2b103911e036
ORCID for Sandrine Willaime-Morawek: ORCID iD orcid.org/0000-0002-1121-6419

Catalogue record

Date deposited: 10 Mar 2017 10:40
Last modified: 14 Mar 2019 01:39

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Contributors

Author: Rui Chen
Author: Wayne Yuk-Wai Lee
Author: Xiao Hu Zhang
Author: Jie Ting Zhang
Author: Sien Lin
Author: Liang Liang Xu
Author: Biao Huang
Author: Fu Yuan Yang
Author: Hai Long Liu
Author: Bin Wang
Author: Lai Ling Tsang
Author: Gang Li
Author: Hsiao Chang Chan
Author: Xiaohua Jiang

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