Introduction: Glioblastoma (GBM) represents the most aggressive malignant brain tumor in adults, with a risible median life expectancy despite gold standard treatment. Novel drug-delivery methods have been explored. Here we evaluated the possibility to use mononuclear cells (MCs) belonging to the monocytic-dendritic lineage as drug-carrier
Methods: MCs were obtained from ten patients harboring a GBM, and from healthy volunteers, considered as controls. GBM tissue was also obtained by patients. MCs were cultured and the adherent population on Fibronectin (FN-MCs), after immunocytochemistry and flow-cytometry characterization, was loaded with Paclitaxel (FN-MCs-PTX). Anti-proliferative and migration activity of FN-MCs-PTX was evaluated in two-dimensional and three-dimensional co-culture assays with red fluorescent U87 Malignant Glioma cells and primary GBM cells. Anti-angiogenic properties of FN-MCs-PTX were tested on cultures with endothelial cells.
Results: Phenotypical characterization showed a high expression of monocytic-dendritic markers in GBM cells and FN-MCs. FN-MCs demonstrated to effectively uptake PTX and to strongly inhibit GBM growth in vitro (p<0,01). Moreover, tumor-induced migration of MCs, although partially affected by the PTX cargo, remained statistically significant when compared to un-primed cells and this was confirmed in a 3D Matrigel model (p<0,01) and in a Trans-well assay (p<0,01). FN-MCs-PTX also disclosed considerable anti-angiogenic properties.
Conclusions: Our results suggest that the Fibronectin-adherent population of MCs isolated from peripheral blood can be an effective tool to inhibit GBM growth. Given the relatively facility to obtain such cells, the short time needed for their culture and drug loading this approach may have potential as an adjuvant therapy for GBM.
Patient Care: it will improve, in the future, the overall suvival and the quality of life
Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the importance of Fibronectin-adherent population of MCs isolated from peripheral blood in cell therapy for glioblastoma 2) Discuss, in small groups, of the future treatments in neuroncology, 3) Identify an effective treatment for Glioblastoma in vitro
References: Fibronectin-adherent peripheral blood derived mononuclear cells as Paclitaxel carriers for glioblastoma treatment: an in vitro study
Marco Schiariti, Francesco Restelli, Paolo Ferroli, Anna Benetti, Angiola Berenzi, Anna Ferri, Valentina Ceserani, Emilio Ciusani, Moris Cadei, Gaetano Finocchiaro, Augusto Pessina, Eugenio Parati, Roberto Pallini and Giulio Alessandri
Cytotherapy IN PRESS