Paclitaxel-releasing mesenchymal stromal cells inhibit in vitro proliferation of human mesothelioma cells.
BACKGROUND
Malignant pleural mesothelioma (MPM) is a rare fatal asbestos-related malignancy originating in the mesothelial cells of the pleura. A platinum-based doublet containing a third-generation antifolate is the front-line standard of care whilst there are no approved second-line treatments for MPM which remains a disease setting to test the efficacy of new therapeutic agents.


METHODS
Bone marrow mesenchymal stromal cells (BM-MSCs) were loaded with pemetrexed (PMX) and paclitaxel (PTX) according to a standardized procedure. Drug release by both PMX- and PTX-primed BM-MSCs (BM-MSCs/PMX and BM-MSCs/PTX) was tested on the in vitro proliferation of a panel of tumor cell lines including NCI-H28 mesothelioma.


RESULTS
The in vitro anticancer activity of pure PTX was significantly higher than that of PMX against all the cell lines tested (14.7 times higher than that of PMX against NCI-H28). Whereas BM-MSCs did not take up and release PMX in amounts effective on mesothelioma, PTX-loaded BM-MSCs dramatically inhibited mesothelioma proliferation.


CONCLUSIONS
PTX-primed mesenchymal stromal cells successfully inhibit the in vitro proliferation of human mesothelioma cells. Further studies and in vivo testing are required to confirm our preliminary in vitro results as a potential new mesothelioma therapy based on cell drug delivery.
Department of Thoracic Surgery, European Institute of Oncology, Milan, Italy. Electronic address: francesco.petrella@ieo.it.
Francesco
F
Petrella
CRC-StaMeTec, Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy; I.R.C.C.S. Galeazzi Orthopedic Institute, Milan, Italy.
Valentina
V
Coccè
CRC-StaMeTec, Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy; I.R.C.C.S. Galeazzi Orthopedic Institute, Milan, Italy.
Carla
C
Masia
Hospital Pharmacy, European Institute of Oncology, Milan, Italy.
Martina
M
Milani
Hospital Pharmacy, European Institute of Oncology, Milan, Italy.
Emanuela Omodeo
EO
Salè
Department of Cerebrovascular Diseases, Fondazione IRCCS Neurological Institute Carlo Besta, Milan, Italy.
Giulio
G
Alessandri
Department of Cerebrovascular Diseases, Fondazione IRCCS Neurological Institute Carlo Besta, Milan, Italy.
Eugenio
E
Parati
CRC-StaMeTec, Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy; I.R.C.C.S. Galeazzi Orthopedic Institute, Milan, Italy.
Francesca
F
Sisto
Oncology Research Center of Mercogliano (CROM), Istituto Nazionale per Lo Studio E La Cura Dei Tumori "Fondazione Giovanni Pascale", IRCCS, Naples, Italy.
Francesca
F
Pentimalli
CRC-StaMeTec, Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy; I.R.C.C.S. Galeazzi Orthopedic Institute, Milan, Italy.
Anna T
AT
Brini
CRC-StaMeTec, Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy; I.R.C.C.S. Galeazzi Orthopedic Institute, Milan, Italy.
Augusto
A
Pessina
Department of Thoracic Surgery, European Institute of Oncology, Milan, Italy; Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy.
Lorenzo
L
Spaggiari
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D008654:Mesothelioma / Q000188:drug therapy*; D000086002:Mesothelioma, Malignant; D017239:Paclitaxel / Q000494:pharmacology*; D000068437:Pemetrexed / Q000494:pharmacology
D000970:Antineoplastic Agents; D000068437:Pemetrexed; D017239:Paclitaxel
Cell drug delivery; Mesenchymal stromal cells; Mesothelioma; Paclitaxel; Pemetrexed