Epigenetic Modification of the CCL5/CCR1/ERK Axis Enhances Glioma Targeting in Dedifferentiation-Reprogrammed BMSCs.
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| 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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| Authors | Rui Chen, Wayne Yuk-Wai Lee, Xiao Hu Zhang, Jie Ting Zhang, Sien Lin, Liang Liang Xu, Biao Huang, Fu Yuan Yang, Hai Long Liu, Bin Wang, Lai Ling Tsang, Sandrine Willaime-Morawek, Gang Li, Hsiao Chang Chan, Xiaohua Jiang |
| Journal | Stem cell reports (Stem Cell Reports) Vol. 8 Issue 3 Pg. 743-757 (03 14 2017) ISSN: 2213-6711 [Electronic] United States |
| PMID | 28216148 (Publication Type: Journal Article) |
| Copyright | Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved. |
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