gms | German Medical Science

62. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgen (PNCH)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

07. - 11. Mai 2011, Hamburg

5-aminolevulinic acid-based photodynamic treatment promotes glioma targeting of human mesenchymal stem cells

Meeting Abstract

  • S. Vogel - Institut für Transplantationsdiagnostik and Zelltherapeutika, Heinrich-Heine-Universität, Düsseldorf
  • N. Etminan - Neurochirurgische Klinik, Heinrich-Heine-Universität, Düsseldorf
  • C. Peters - Institut für Transplantationsdiagnostik and Zelltherapeutika, Heinrich-Heine-Universität, Düsseldorf; Neurochirurgische Klinik, Heinrich-Heine-Universität, Düsseldorf
  • M. Sabel - Neurochirurgische Klinik, Heinrich-Heine-Universität, Düsseldorf
  • R.V. Sorg - Institut für Transplantationsdiagnostik and Zelltherapeutika, Heinrich-Heine-Universität, Düsseldorf

Deutsche Gesellschaft für Neurochirurgie. Polnische Gesellschaft für Neurochirurgen. 62. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgen (PNCH). Hamburg, 07.-11.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. DocMO.07.08

DOI: 10.3205/11dgnc045, URN: urn:nbn:de:0183-11dgnc0457

Veröffentlicht: 28. April 2011

© 2011 Vogel 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 vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective: Glioblastoma gene therapy tries to exploit the tropism of mesenchymal stem cells (MSC) for the tumor cells, using MSC as a vector to deliver the therapeutic agents. MSC are known to be the home for sites of apoptosis and thus the type of cell death induced by another therapeutic approach in GBM, aminolevulinic acid-mediated photodynamic therapy (ALA/PDT). Therefore, we studied whether ALA/PDT treatment improves MSC homing in a human glioma spheroid model.

Methods: The chemoattractive activity of ALA/PDT-treated spheroids of the human glioma cell lines U87 and U251 were studied in an under-agarose migration assay. Expression of hepatocyte growth factor (HGF) in glioma cells and of its receptor, c-Met, on MSC was determined by ELISA and flow-cytometry, respectively. The contribution of HGF to MSC migration towards spheroids was determined using neutralizing anti-HGF antibodies.

Results: U87 and U251 glioma cell spheroids revealed baseline expression of HGF (5.60 ± 0.03 ng/ml and 2.89 ± 0.13, respectively), which was not or only moderately changed after treatment of spheroids with irradiation or ALA alone. ALA/PDT treatment, however, resulted in the significant upregulation of HGF (14.77 ± 0.48 ng/ml; p = 0.0028, 8.96 ± 0.21 ng/ml; p = 0.0016, respectively). MSC expressed the HGF receptor, c-Met, and migrated towards untreated spheroids. There was no change in the migratory response when spheroids were treated with irradiation or ALA alone (p > 0.05). In contrast, a 3.3- (p = 0.0096) and 3.7-fold (p = 0.0018) increase in migration towards the ALA/PDT treated U87 and U251 spheroids was observed, respectively. This migration of MSC towards the spheroids, irrespective of whether they were treated or untreated, was nearly completely inhibited by an anti-HGF neutralizing antibody.

Conclusions: Glioma cells express HGF, which contributes to the attraction of MSC. ALA/PDT treatment augments HGF release, which is associated with a threefold increase in MSC migration towards the tumor cells. Therefore, a combination of MSC-delivered gene therapy with ALA/PDT may improve targeting of the tumor.