gms | German Medical Science

61. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC) im Rahmen der Neurowoche 2010
Joint Meeting mit der Brasilianischen Gesellschaft für Neurochirurgie am 20. September 2010

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

21. - 25.09.2010, Mannheim

5-ALA based photodynamic therapy (PDT) in glioblastoma-derived stem cell-enriched cultures

Meeting Abstract

  • Christian Ewelt - Klinik für Neurochirurgie, Heinrich-Heine Universität, Düsseldorf, Deutschland; Klinik für Neurochirurgie, Westfälische Wilhelms Universität, Münster, Deutschland
  • Nima Etminan - Klinik für Neurochirurgie, Heinrich-Heine Universität, Düsseldorf, Deutschland
  • Sarah Jauernik - Klinik für Neurochirurgie, Heinrich-Heine Universität, Düsseldorf, Deutschland
  • Hans-Jakob Steiger - Klinik für Neurochirurgie, Heinrich-Heine Universität, Düsseldorf, Deutschland
  • Walter Stummer - Klinik für Neurochirurgie, Westfälische Wilhelms Universität, Münster, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 61. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC) im Rahmen der Neurowoche 2010. Mannheim, 21.-25.09.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. DocV1550

DOI: 10.3205/10dgnc027, URN: urn:nbn:de:0183-10dgnc0279

Veröffentlicht: 16. September 2010

© 2010 Ewelt 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: Considerable attention is being focussed on basic and translational research concerning glioblastoma stem cells, their tumorigenic potential and their resistance to radio- and chemotherapy. 5-ALA based photodynamic therapy (PDT) induces cell death in the C6 glioma spheroid model and appears to improve clinical outcome in patients suffering from recurrent glioblastoma by causing long-sustaining responses. In order to study the acute effects of ALA/PDT on multipotent glioblastoma cell lines, we used a three-dimensional cell culture system.

Methods: Glioblastoma-derived stem cell-enriched cultures were treated with ALA/PDT. Human glioma spheroids (U 373) served as controls. Cell spheroids were incubated for 4 h in 0/4/12,5/18 µg/ml ALA in 5% CO2 in room air with subsequent irradiation using a diode laser (lambda = 635 nm, 40 mW/cm2, total fluence 25 J/cm2). Control groups were "laser only", "ALA only", and "no drug no light".The stem cell lines were analyzed for expression profiles like CD133 and its intracellular concentration after ALA-incubation by fluorescence activated cell sorting (FACS). Cell death was analyzed by colorimetric assay (WST-1 based) for the nonradioactive quantification of cell proliferation, cell viability and cytotoxicity.

Results: Subsequent ALA/PDT after incubation in 5% CO2 provided incomplete cell death in tumor spheroids in relation to “no drug, no light” controls: 0µg/ml ALA: 99,54%, 4 µg/ml ALA: 122,02%, 12,5 µg/ml ALA: 42,45% and 18 µg/ml ALA: 21,00%. In incompletely damaged spheroids viable cells were restricted to spheroid centers. The rate of cell death in all control groups was negligible. The cytotoxicity of the stem cells after ALA/PDT was equivalent to those results of the U373 glioma spheroids. Expression of CD133 was confirmed in all stem cell lines with typical full spheroid growth pattern.

Conclusions: PDT of experimental glioblastoma stem cell lines results in significant cell death after irradiation. This might be an explanation for observed long-sustaining PDT effects in recurrent glioblastomas in patients.