Epigenetic Modification of the CCL5/CCR1/ERK Axis Enhances Glioma Targeting in Dedifferentiation-Reprogrammed BMSCs.

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

SUBMITTER: Chen R 

PROVIDER: S-EPMC5355636 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature