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

Brain tumor tropism of transplanted human neural stem cells – The Role of vascular endothelial growth factor-A as a chemoattractant

Hirntumor tropismus-transplantierter menschlicher neuraler Stammzellen - Die Rolle von VEGF-A als chemotaktischer Faktor

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
  • K. Aboody - Divisions of Hematology and Bone Marrow Transplantation, City of Hope Cancer Center & Beckman Research Institute, Duarte, USA
  • S. U. Kim - Division of Neurology, UBC Hospital, University of British Columbia, Vancouver, CDN
  • 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

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 03.31

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2004/04dgnc0314.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

The transplantation of neural stem cells (NSCs) offers a new potential opportunity for neurorestoration or as a cell-based vehicle for the delivery of therapeutic gene products in a variety of neurological diseases. This is mainly based on the enormous capacity of NSCs to migrate through the brain to target brain tumors and other pathological sites like e.g. in multiple sclerosis, stroke and traumatic brain injuries. However, the signals involved in this tropism are poorly defined.

Methods

In this study we assessed 56 human tissue extracts prepared from gliomas of different histological grade, brain metastasis, meningiomas and non-tumoral brain tissue for their content of the well-known angiogenic factors VEGF165, PlGF and SF/HGF. Analysis of human NSC migration in the modified Boyden Chamber assay in response to these defined tissue extracts, the recombinant human angiogenic growth factors and in presence of specific neutralizing antibodies was performed. To address the relevance of our in vitro findings, local intracerebral microinfusions of VEGF165, SF/HGF or PBS via osmotic mini-pumps were established in the left forebrain of nude mice and human NSCs were stereotactically transplanted in the right frontal lobe. Histological analysis of NSC distribution was performed five and nine days later.

Results

While VEGF165 and SF/HGF but not PlGF were able to induce NSC migration in vitro, non-linear regression analysis revealed a strong correlation only between the VEGF165 content of the tissue extracts and their migration-inducing effects. Local intracerebral infusions of VEGF165 induced an extensive migration of human NSCs towards the contralateral VEGF165 infused hemisphere already after five days. SF/HGF or PBS infusions did not result in a similar phenomenon although some NSCs were present at the injury site of the brain cannula.

Conclusions

These results demonstrate that VEGF165 is a strong chemoattractant for transplanted human neural stem cells in the adult brain and suggest that VEGF itself or VEGF-induced angiogenesis may be a relevant guidance signal for NSC tropism towards brain tumors and other pathological sites.