Artikel
Interactions of neural stem cells and glioma cells in a three-dimensional organotypic brain slice co-culture system
Interaktion von neuralen Stammzellen und Gliomzellen in einem organotypischen Hirnschnitt Kokultur System
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Autoren
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O. Heese
- Klinik für Neurochirurgie, Universitätsklinikum Hamburg-Eppendorf
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D. Zirkel
- Klinik für Neurochirurgie, Universitätsklinikum Hamburg-Eppendorf
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M. Westphal
- Klinik für Neurochirurgie, Universitätsklinikum Hamburg-Eppendorf
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K. Lamszus
- Klinik für Neurochirurgie, Universitätsklinikum Hamburg-Eppendorf
| Veröffentlicht: | 4. Mai 2005 |
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Gliederung
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Objective
Primary human brain tumours are largely refractory to currently available treatment modalities due to the degree to which they infiltrate surrounding brain tissue. Various in vivo studies have demonstrated a migration tendency of neural stem cells (NSCs) towards intracranial gliomas, making these cells a potential carrier for delivery of therapeutic genes to disseminated gliomas. We analyzed NSC migration in response to glioma stimuli in an organotypic brain slice model in order to mimic the in vivo microenvironment including the three-dimensional architecture of murine brain tissue.
Methods
The chemotactic effects of 5 glioma cell lines and their responding conditioned media on the murine NSC line C17.2 in a co-culture organotypic brain slice system was assessed. 400 µm coronal sections of 6 day old mouse brain were used for the experiments. NSCs and glioma cells were identified inside the brain slice by pre-implantation staining with DiI and DiO. Migration of NSCs and glioma cells inside the brain slices was characterized and quantified using a confocal laser microscope on day 2, 6 and 12.
Results
C17.2 NSCs migrate inside the brain slices and seem to follow preserved anatomic structures. Migration of the NSCs was modified by conditioned media of glioma cells. Conditioned media of two glioma cell lines augmented migration of NSCs up to 50% compared to controls. In two gliomas conditioned media stimulation was only moderate (20%). Conditioned media of one cell line produced inhibition of NSC migration. Co-culturing of NSCs and glioma cells inside the brain slice resulted in a directed migration of both cell types towards each other in 3 of 5 glioma cell lines including close cell-to-cell contact.
Conclusions
The organotypic brain slice model displays several advantages over less complex in vitro migration models since a physiologic microenvironment of brain tissue and a three-dimensional architecture is preserved. Migration of NSCs towards gliomas in our assay system seems to depend on individual phenotypic characteristics and growth factor release patterns of the target tissue.
