gms | German Medical Science

58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

26. bis 29.04.2007, Leipzig

Risk potential of adult human mesenchymal stem cells used as cellular vectors in glioma therapy

Risikopotential adulter humaner mesenchymaler Stammzellen in der Verwendung als zellulärer Vektor in der Gliomtherapie

Meeting Abstract

  • corresponding author C. Schichor - Klinik für Neurochirurgie, Ludwig-Maximilians-Universität München, Klinikum Großhadern
  • E. Sobala - Klinik für Neurochirurgie, Ludwig-Maximilians-Universität München, Klinikum Großhadern
  • S. Grau - Klinik für Neurochirurgie, Ludwig-Maximilians-Universität München, Klinikum Großhadern
  • B. Krebs - Klinik für Neuropathologie, Ludwig-Maximilians-Universität München, Klinikum Großhadern
  • J.-C. Tonn - Klinik für Neurochirurgie, Ludwig-Maximilians-Universität München, Klinikum Großhadern
  • R. Goldbrunner - Klinik für Neurochirurgie, Ludwig-Maximilians-Universität München, Klinikum Großhadern

Deutsche Gesellschaft für Neurochirurgie. 58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC). Leipzig, 26.-29.04.2007. Düsseldorf: German Medical Science GMS Publishing House; 2007. DocP 085

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2007/07dgnc340.shtml

Veröffentlicht: 11. April 2007

© 2007 Schichor 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: Much effort has been put into establishing human multipotent cells as carriers for malignant glioma therapy. We already described VEGF-dependent interaction of adult human mesenchymal stem cells (hMSC) and glioma cells in vitro and characterized glioma-modulated invasive hMSC-behaviour glioma infiltrated brain in vivo. In this study, we evaluated the potential risks of adult hMSC in the use as a cellular vector for glioma therapy.

Methods: hMSC were isolated from bone marrow biopsies carried out for haematological indications. Primary hMSC were held under long-term conditioning in order to rule out genetic instability due to cell culture artifacts. Cells were grown with either glioma-conditioned or normal medium. To assess eventually acquired malignant potential, colony forming assays were performed and proliferation curves were documented. For in vivo assessment, cells were (i) implanted intracranially without any presence of glioma cells, (ii) administered locally in U373 glioma bearing nude rats, (iii) applied systemically in U373 glioma bearing nude rats.

Results: In vivo, we observed 1 case out of 40 cases, in which primary hMSC formed a tumor-like formation, surrounded by glioma cells. Under long-term culture conditions, most of the hMSC showed the well-known phenomenon of senescence (growth arrest). Out of a hMSC panel of 8 patients, 2 probes showed a sudden change of phenotype with a strong increase of proliferation after 8 weeks culture with glioma conditioned medium. These cells also exhibited a malignant phenotype in terms of intense colony forming in vitro.

Conclusions: Despite hMSC seem to be effective cellular carriers for anti-glioma therapy due to their strong glioma tropism, there is a risk of a malignant transformation of primary isolated hMSC after contact with glioma cells or even glioma-conditioned medium. This observation might have impact on the conception of future cell based therapies.