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Int. J. Mol. Sci. 2015, 16(5), 9936-9948;

Aminolevulinic Acid-Mediated Photodynamic Therapy of Human Meningioma: An in Vitro Study on Primary Cell Lines

Department of Neurosurgery, Universitätsklinikum Düsseldorf, Heinrich Heine Universität, 40225 Düsseldorf, Germany
Center for Molecular Medicine, Universität zu Köln, 50931 Cologne, Germany
Institute for Neurophysiology, Universität zu Köln, 50931 Cologne, Germany
Department of Neuropathology, Regensburg University Hospital, 93042 Regensburg, Germany
Wilhelm Sander-NeuroOncology Unit, Regensburg University Hospital, 93042 Regensburg, Germany
Department of Neurosurgery, Universitätsklinikum Münster, Westfälische Wilhelms-Universität, 48149 Münster, Germany
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Academic Editors: Michael R. Hamblin and Ying-Ying Huang
Received: 21 March 2015 / Revised: 5 April 2015 / Accepted: 27 April 2015 / Published: 30 April 2015
(This article belongs to the Special Issue Advances in Photodynamic Therapy)
Full-Text   |   PDF [1464 KB, uploaded 30 April 2015]   |  


Objective: Five-aminolevulinic acid (5-ALA)-induced porphyrins in malignant gliomas are potent photosensitizers. Promising results of ALA-PDT (photodynamic therapy) in recurrent glioblastomas have been published. Recently, 5-ALA-induced fluorescence was studied in meningioma surgery. Here, we present an experimental study of ALA-PDT in an in vitro model of primary meningioma cell lines. Methods: We processed native tumor material obtained intra-operatively within 24 h for cell culture. Epithelial membrane antigen (EMA) immunohistochemistry was performed after the first passage to confirm that cells were meningioma cells. For 5-ALA-PDT treatment, about 5000 cells per well were seeded in 20 wells of a blank 96-well plate. Each block of 4 wells was inoculated with 150 µL of 0, 25, 50 and 100 µg/mL 5-ALA solutions; one block was used as negative control without 5-ALA and without PDT. Following incubation for 3 h PDT was performed using a laser (635 nm, 18.75 J/cm2). The therapeutic response was analyzed by the water soluble tetrazolium salt (WST-1) cell viability assay 90 min after PDT. Results: 5-ALA-PDT was performed in 14 primary meningioma cell lines. EMA expression was verified in 10 primary cell cultures. The remaining 4 were EMA negative and PDT was without any effect in these cultures. All 10 EMA-positive cell lines showed a significant and dose-dependent decrease in viability rate (p < 0.001). Cell survival at 5-ALA concentrations of 12.5, 25, 50 and 100 μg/mL was 96.5% ± 7.6%, 67.9% ± 29.9%, 24.0% ± 16.7% and 13.8% ± 7.5%, respectively. For the negative controls (no 5-ALA/PDT and ALA/no PDT), the viability rates were 101.72% ± 3.5% and 100.17% ± 3.6%, respectively. The LD50 for 5-ALA was estimated between 25 and 50 µg/mL. Conclusion: This study reveals dose-dependent cytotoxic effects of 5-ALA-PDT on primary cell lines of meningiomas. Either 5-ALA or PDT alone did not affect cell survival. Further efforts are necessary to study the potential therapeutic effects of 5-ALA-PDT in vivo. View Full-Text
Keywords: 5-ALA; aminolevulinic acid; PDT; photodynamic therapy; meningioma; in vitro; primary cell culture 5-ALA; aminolevulinic acid; PDT; photodynamic therapy; meningioma; in vitro; primary cell culture

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El-Khatib, M.; Tepe, C.; Senger, B.; Dibué-Adjei, M.; Riemenschneider, M.J.; Stummer, W.; Steiger, H.J.; Cornelius, J.F. Aminolevulinic Acid-Mediated Photodynamic Therapy of Human Meningioma: An in Vitro Study on Primary Cell Lines. Int. J. Mol. Sci. 2015, 16, 9936-9948.

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