Artikel
Adult human mesenchymal stem cells as treatment vectors in glioma therapy: Migratory and invasive patterns
Adulte mesenchymale Stammzellen als Vektoren einer Gliomtherapie: Migrations- und Invasionseigenschaften
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Autoren
Veröffentlicht: | 23. April 2004 |
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Gliederung
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Objective
Since K. Aboody (2000) could show that murine neural stem cells migrate through brain tissue towards experimental gliomas, much effort has been put into establishing human multipotent cells as carriers for malignant glioma therapy. The aims of our study therefore were, (1) to characterize factors that influence active movement of neural stem cells in the environment of a tumour 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. Tumour-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 tumour-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.