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Int. J. Mol. Sci. 2015, 16(5), 9936-9948; doi:10.3390/ijms16059936

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

1
Department of Neurosurgery, Universitätsklinikum Düsseldorf, Heinrich Heine Universität, 40225 Düsseldorf, Germany
2
Center for Molecular Medicine, Universität zu Köln, 50931 Cologne, Germany
3
Institute for Neurophysiology, Universität zu Köln, 50931 Cologne, Germany
4
Department of Neuropathology, Regensburg University Hospital, 93042 Regensburg, Germany
5
Wilhelm Sander-NeuroOncology Unit, Regensburg University Hospital, 93042 Regensburg, Germany
6
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)
View Full-Text   |   Download PDF [1464 KB, uploaded 30 April 2015]   |  

Abstract

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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MDPI and ACS Style

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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