gms | German Medical Science

59. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
3. Joint Meeting mit der Italienischen Gesellschaft für Neurochirurgie (SINch)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

01. - 04.06.2008, Würzburg

Differential tumor homing and infiltration of exogenous vs. endogenous neural stem cells in an intracerebral murine metastasis model

Differentielle Infiltration und selektive Migration von exogen zugeführten vs. endogenen neuralen Stammzellen in einem murinen Model der zerebralen Metastasierung

Meeting Abstract

  • corresponding author P. Weigel - Klinik für Neurochirurgie, Universitätsklinikum Carl Gustav Carus, Dresden
  • R. Glass - Cellular Neuroscience Group, Max Delbrück Center for Molecular Medicine, Berlin
  • M. Synowitz - Klinik für Neurochirurgie, Campus Virchow, Charité - Universitätsmedizin Berlin
  • H. Kettenmann - Cellular Neuroscience Group, Max Delbrück Center for Molecular Medicine, Berlin
  • G. Schackert - Klinik für Neurochirurgie, Universitätsklinikum Carl Gustav Carus, Dresden
  • M. Kirsch - Klinik für Neurochirurgie, Universitätsklinikum Carl Gustav Carus, Dresden

Deutsche Gesellschaft für Neurochirurgie. Società Italiana di Neurochirurgia. 59. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3. Joint Meeting mit der Italienischen Gesellschaft für Neurochirurgie (SINch). Würzburg, 01.-04.06.2008. Düsseldorf: German Medical Science GMS Publishing House; 2008. DocDI.04.08

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2008/08dgnc174.shtml

Veröffentlicht: 30. Mai 2008

© 2008 Weigel et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective: Neural stem cells have been used extensively as an exogenous source of therapeutic vehicles that will unspecifically target a variety of intracerebral pathologies including trauma sites, ischemic areas and tumors. Among the chemotactic factor governing NSC homing to these sites relate to the CXCR4-SDF-1, the c-Kit–SCF, and the Flk-1-VEGF signaling molecules. Most of the oncological investigations are based on intracerebral glioma models. However, intracerebral metastases have a much higher incidence than primary brain tumors. The purpose of the present study was to investigate the homing properties of both exogenously delivered and of endogenous neural stem cells to metastatic intracerebral lesions.

Methods: K1735 murine melanoma cells were deposited into the right frontal lobe of 6 week-old wild-type mice (n=11) and of nestin-GFP transgenic C57BL/6 mice (n=7). Wild-type mice were allowed to grow the tumor for 10 days before they were subjected to an intraarterial injection of 100,000 GFP-NSC which were obtained from newborn GFP-transgenic C57BL/6 mice. 24 days after tumor cell implantation, all animals were killed, the brains removed and subjected to immunohistochemical and fluorescence microscopy analysis.

Results: Exogenously delivered NSC revealed a strong homing effect to intracerebral focal metastases. These cells were able to infiltrate metastases even at small sizes of <300 µm. The number of tumor-infiltrating, nestin+ NSC was significantly higher within the tumor than in the non-tumor bearing brain. Endogenous neural stem cells occurred at high densities along the rim of the metastatic tumor. In contrast to exogenous NSC, endogenous NSC were not seen within the tumor. There was no significant difference on the average tumor size (endo: 3.9 mm vs. exo: 3.2 mm diameter).

Conclusions: Exogenous and endogenous NSC reveal a high tumor-homing potential, however, endogenous NSC were not detected within the tumor. Further investigations need to clarify whether this is due to an improved ability of endogenous NSC to differentiate within the tumor and concomitantly escape GFP-based detection or whether ex vivo conditioning selects for a higher migratory potential of exogenous NSC.