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Adult
human mesenchymal stem cells: VEGF-driven interaction with glioma
cells in vitro Christian Schichor, Nima Etminan, Sabine Miebach, Jörg-Christian Tonn, Tobias Birnbaum,
Claudio Padovan, Roland Goldbrunner
Univ. Clinic LMU Munich Grosshadern, Munich, Germany, Neurol.
University Clinic, LMU Munich Grosshadern, Munich, Germany
Objective. Much
effort has been put into establishing human multipotent cells as
carriers for malignant glioma therapy.
The aim of our study were, (1) to characterize factors that influence
active movement of stem cells in the environment of a tumor
infiltrated brain and, (2) to test human adult mesenchymal stem cells
(MSCs), which are easily available through bone marrow biopsy, for
their migratory and invasive behaviour and their interaction with
human gliomas.
Methods. Human
MSC were isolated from bone marrow biopsies carried out for
haematological indications.
Only early passages were used for the experiments.
Migration of human adult MSC- and rodent embryonal NSC-spheroids (cell
line C17.2) was studied on different matrices: Laminin, Tenascin and
plastic.
Tumor-conditioned medium as well as VEGF were added in order to
evaluate the role of glioma derived factors.
To assess invasion, confrontational co-cultures of glioma- (U373 GFP,
C6 GFP, C6 VEGF sense, C6 VEGF antisense transfected) and stem
cell-spheroids (human MSC, rodent NSC respectively) were
investigated.
Invasion was visualized by light and confocal microscopy.
Results.
Migration of both rodent embryonal NSC and human adult MSC was fastest
on Laminin, when compared to Tenascin and plastic.
VEGF as well as tumor-conditioned medium significantly increased NSC
and MSC migration.
Human MSCs showed an extensive invasion into glioma spheroids, even
more than embryonal rodent NSCs.
Invasion of NSC into VEGF sense C6 spheroids was much more rapid than
invasion into VEGF antisense spheroids.
Conclusions.
Both, NSC and MSC, show intensive migratory behaviour in presence of
glioma cells and glioma-conditioned medium.
Obviously, VEGF is a crucial factor in enhancing stem cell
motility.
Since human MSC invade glioma spheroids even faster than rodent NSC,
they proved to be hopeful candidates for a future role as treatment
vectors.
Copyright © 2005 American
Association for Cancer Research. All rights reserved.
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