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

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-1α (SDF-1α) 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-1α receptor, CXCR4, on human umbilical cord blood-derived 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-1α treatment increased the migration capacity of hUCB-MSCs in a dose-dependent manner and inhibition of SDF-1α or CXCR4 by treatment with the anti-SDF-1α 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-1α/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.

journal_name

Int J Oncol

authors

Park SA,Ryu CH,Kim SM,Lim JY,Park SI,Jeong CH,Jun JA,Oh JH,Park SH,Oh W,Jeun SS

subject

Has Abstract

pub_date

2011-01-01 00:00:00

pages

97-103

issue

1

eissn

1019-6439

issn

1791-2423

journal_volume

38

pub_type

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