CXCR4-transfected human umbilical cord blood-derived mesenchymal stem cells exhibit enhanced migratory capacity toward gliomas.
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.
Department of Biomedical Science, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
Soon A
SA
Park
Chung Heon
CH
Ryu
Seong Muk
SM
Kim
Jung Yeon
JY
Lim
Sang In
SI
Park
Chang Hyun
CH
Jeong
Jin Ae
JA
Jun
Ji Hyeon
JH
Oh
Sun Hwa
SH
Park
Wonil
W
Oh
Sin-Soo
SS
Jeun
D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
D019718:Receptors, CXCR4