CXCR4-transfected human umbilical cord blood-derived mesenchymal stem cells exhibit enhanced migratory capacity toward gliomas

Abstract

Abstract. Mesenchymal stem cells (MSCs) can be used as a delivery vehicle for gene therapy against brain tumors, because these cells have a migratory capacity toward glioma cells. Soluble factors including chemokines or growth factors expressed and released by glioma cells mediate the tropism of MSCs for gliomas. Among them, stromal cell-derived factor-1· (SDF-1·) has been identified as a key molecule related to the tropism of MSC in many cancers containing gliomas. In this study, we found that overexpression of the SDF-1· receptor, CXCR4, on human umbilical cord bloodderived MSCs (hUCB-MSCs) enhanced the migratory capacity of MSCs toward gliomas. We showed that hUCB-MSCs have the migration ability toward the glioma cell lines and primary glioma cells. SDF-1· treatment increased the migration capacity of hUCB-MSCs in a dose-dependent manner and inhibition of SDF-1· or CXCR4 by treatment with the anti-SDF-1· or the CXCR4 antagonist AMD3100 blocked the migration capacity of hUCB-MSCs toward glioma cells. Furthermore, CXCR4-overexpressed hUCB-MSCs (hMSCs-CXCR4) showed a stronger migration capacity toward glioma cells in vitro compared with control MSCs, and also exhibited enhanced migration to glioma cells in an intracranial human malignant glioma xenograft model. These results indicate that SDF-1·/CXCR4 could be involved in recruitment of hUCB-MSCs to glioma cells and that overexpression of CXCR4 may be a useful tool for stem cell-based glioma therapy.

Combination of Mesenchymal Stem Cell-Delivered Oncolytic Virus with Prodrug Activation Increases Efficacy and Safety of Colorectal Cancer Therapy

“…This can be improved by in vivo experiment using imaging to demonstrate whether this priming attracts more MSCs to the tumors. However, there is a large amount of evidence showing that increased CXCR4 expression on cell surface can promote tumor tropism in vivo [ 31 , 39 , 40 ], and efforts were also made in the current study to minimize animal suffering and to reduce the number of animals used. These are the reasons why we did not conduct these animal experiments.…”

Contribution of SDF-1a/CXCR4 Signaling to Brain Development and Glioma Progression

“…Tabatabai et al [131] demonstrated that irradiation induces tumor satellite formation at 21 days after intracerebral implantation of glioma. Irradiation enhances the tropism of bone marrow-derived cells (BMDCs) and HPCs to the gliomas, the proliferation of HPCs, and the vasculogenesis of BMDCs [131,180,186]. During these processes, SDF-1α has been identified as a key molecule.…”