title: Human CD14+ cells loaded with Paclitaxel inhibit in vitro cell proliferation of glioblastoma.
abstract: OBJECTIVE
  In attempting to develop new strategies to circumvent the immunosuppression associated with glioblastoma (GB), novel approaches have been designed using dendritic cell (DC)-based vaccination, which is considered a promising strategy to attack high-grade glioma. In previous studies, we demonstrated that human mesenchymal stromal cells without genetic manipulation but primed with Paclitaxel (PTX) acquire a potent anti-tumor activity, providing an interesting new biological approach for drug delivery. On the basis of these results, we here investigated whether both CD14+ and their derived DCs may behave like mesenchymal stromal cells acquiring anti-tumor activity on priming with PTX.
  
  
  METHODS
  Human CD14+ cells were isolated from peripheral blood. Fluorescence-activated cell sorter analysis was performed to determine the purity of CD14+ and their differentiation into mature DCs. Cells were primed by incubation with 1 μg/mL of PTX for 24 h, and the PTX released by cells was assessed by mass spectrometry analysis. Anti-tumor activity was checked by testing the conditioned medium (CM) on the proliferation of U87 MG, a GB cell line.
  
  
  RESULTS
  Both CD14+ and DCs were able to incorporate PTX and release the drug in the CM in a time-dependent manner (maximal release over 24 h). The addition of CM from CD14+ and DCs loaded with PTX strongly inhibits proliferation of U87 MG cells.
  
  
  CONCLUSIONS
  Our results are the first demonstration that peripheral blood-derived CD14+ and DCs, in addition to their application for immunotherapy for GB, could also be used to delivery anti-cancer drugs, such as PTX, to kill GB cells.
authors.affiliation: Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Bonomi
authors.affiliation: Cell Therapy Production Unit, Fondazione Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS) Neurological Institute C. Besta, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Lisini
authors.affiliation: Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Stefania Elena
authors.initials: SE
authors.lastname: Navone
authors.affiliation: Cell Therapy Production Unit, Fondazione Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS) Neurological Institute C. Besta, Milan, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Frigerio
authors.affiliation: Cellular Neurobiology Laboratory, Department of Cerebrovascular Diseases, Fondazione IRCCS Neurological Institute C. Besta, Milan, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Dossena
authors.affiliation: Laboratory of Clinical Pathology and Neurogenetic Medicine, Fondazione IRCCS Neurological Institute C. Besta, Milan, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Ciusani
authors.affiliation: Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Rampini
authors.affiliation: Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marfia
authors.affiliation: Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Coccè
authors.affiliation: Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Cavicchini
authors.affiliation: Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Sisto
authors.affiliation: Cellular Neurobiology Laboratory, Department of Cerebrovascular Diseases, Fondazione IRCCS Neurological Institute C. Besta, Milan, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Parati
authors.affiliation: Unit of Neuro-Immunology, Fondazione IRCCS Neurological Institute C. Besta, Milan, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Mantegazza
authors.affiliation: Division of Biochemistry and Genetics, Fondazione IRCCS Neurological Institute C. Besta, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Rimoldi
authors.affiliation: Division of Biochemistry and Genetics, Fondazione IRCCS Neurological Institute C. Besta, Milan, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Rizzetto
authors.affiliation: Cellular Neurobiology Laboratory, Department of Cerebrovascular Diseases, Fondazione IRCCS Neurological Institute C. Besta, Milan, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Alessandri
authors.affiliation: Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy. Electronic address: augusto.pessina@unimi.it.
authors.forename: Augusto
authors.initials: A
authors.lastname: Pessina
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D019496:Cancer Vaccines / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation; D064987:Cell- and Tissue-Based Therapy; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D003713:Dendritic Cells / Q000276:immunology*; D016503:Drug Delivery Systems; D005909:Glioblastoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells; D017239:Paclitaxel / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D017077:Culture Media, Conditioned; D018950:Lipopolysaccharide Receptors; D017239:Paclitaxel
keywords: CD14+ cells; Taxol; drug uptake; glioblastoma