Artikel
Vascular endothelial growth factor (VEGF) is significantly involved in glioma-induced migration of adult human mesenchymal stem cells
VEGF ist ein signifikanter Faktor der Gliom-induzierten Migration adulter mesenchymaler Stammzellen
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Autoren
Veröffentlicht: | 4. Mai 2005 |
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Gliederung
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Objective
Much effort has been put into establishing human multipotent cells as carriers for malignant glioma therapy. We already described interaction of adult human mesenchymal stem cells (hMSC), which are easily available through bone marrow biopsy and glioma cells in vitro. Aim of our study was to characterise glioma-induced, VEGF-dependent migratory and invasive MSC- behaviour.
Methods
Human MSC were isolated from bone marrow biopsies carried out for hematological indications. Only early passages were used for the experiments. Chemokinetic activity of hMSC in response to glioma-conditioned medium as well as VEGF was evaluated using a modified Boyden chamber assay. Confrontational co-cultures of glioma- (U373 GFP, C6 GFP, C6VEGF sense, C6 VEGF antisense transfected) and stem cell-spheroids (hMSC) were investigated. Invasion was visualised by light and confocal microscopy. VEGF-secretion by gliomas was analysed by ELISA. Expression of VEGF-receptor flk-1 in hMSCs was assessed immunohistochemically.
Results
ELISA-analysis showed high VEGF-expression in all glioma cell lines. VEGF as well as tumour-conditioned medium significantly increased hMSC migration and invasion. hMSC showed an extensive invasion into glioma spheroids. Addition of anti-human VEGF antibody significantly inhibited the VEGF-dependent effect of glioma-driven hMSC-invasion.
Conclusions
hMSC show intensive migratory and invasive behaviour in presence of glioma cells and glioma-conditioned medium. Obviously, VEGF is a crucial factor in enhancing stem cell motility. hMSC proved to be hopeful candidates for a future role as glioma treatment vectors.