gms | German Medical Science

55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

25. bis 28.04.2004, Köln

Pro-drug converting neural stem cells for the local intracerebral chemotherapy of human glioblastoma xenografts

Genetisch-modifizierte neurale Stammzellen zur lokalen Chemotherapie in einem experimentellen Glioblastom-Modell

Meeting Abstract

  • corresponding author Nils Ole Schmidt - Neurosurgical Oncology Laboratory, Brigham & Women's Hospital / Harvard Medical School, Boston /USA; Klinik für Neurochirurgie, Universitätsklinikum HH-Eppendorf, Hamburg
  • M. Ziu - Neurosurgical Oncology Laboratory, Brigham & Women's Hospital / Harvard Medical School, Boston /USA
  • P. M. Black - Neurosurgical Oncology Laboratory, Brigham & Women's Hospital / Harvard Medical School, Boston /USA
  • R. S. Carroll - Neurosurgical Oncology Laboratory, Brigham & Women's Hospital / Harvard Medical School, Boston /USA
  • K. Aboody - City of Hope Cancer Center & Beckman Research Institute, Duarte /USA

Deutsche Gesellschaft für Neurochirurgie. Ungarische Gesellschaft für Neurochirurgie. 55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie. Köln, 25.-28.04.2004. Düsseldorf, Köln: German Medical Science; 2004. DocP 03.32

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2004/04dgnc0315.shtml

Veröffentlicht: 23. April 2004

© 2004 Schmidt 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

Previous reports have demonstrated that neural stem cells (NSCs) distribute throughout experimental intracranial gliomas and are able to “track” invading tumor cells when implanted in the adult rodent brain. Based on this extensive tumor tropism NSCs are attractive candidates as a potential delivery system for therapeutic gene products in the treatment of invasive gliomas.

Methods

Here, we investigated the therapeutic effectiveness of glioma-targeting NSCs expressing cytosine deaminase (CD) to convert systemically administered non-toxic pro-drug 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU), which diffuses out of the NSCs and selectively kills dividing tumor cells. Murine NSCs C17.2 (lacZ/cytosine deaminase positive or negative) were stereotactically implanted distant (occipital) to well-established intracerebral U87 human glioblastoma xenografts in adult nude mice. Systemic treatment with 5-FC at 500 mg/kg/d started three days after NSCs injection. Tumor growth was assessed by T1-Gd enhanced magnetic resonance imaging and NSCs distribution by X-gal immunohistochemistry.

Results

Intracerebral implantation of 1.5 x 105 NSCs-CD followed by systemic administration of 5-FC inhibited the tumor growth as assessed by MRI 14 days after treatment start. Furthermore, the survival was significantly prolonged when compared to the animals of the control groups (no NSC implantation, implantation of NSC-mock plus 5-FC treatment or implantation of NSC-CD but no 5-FC). Histological analysis demonstrated the intratumoral distribution of NSCs although the cells were initially implanted distant from the main tumor mass. However, we were not able to detect any NSCs based on X-gal immunohistochemistry in the brains of nude mice analyzed later than 22 days after NSC injection.

Conclusions

These results indicate that NSCs represent a potent new delivery system for the local intracerebral treatment of gliomas. However, NSCs may not survive within the tumor environment for a prolonged time and therefore larger numbers of NSCs or multiple injections should be considered. Future studies need to address the interaction of transplanted NSCs with the tumor environment.