Francesco Petrella1, Valentina Coccè2, Carla Masia2, Martina Milani3, Emanuela Omodeo Salè3, Giulio Alessandri4, Eugenio Parati4, Francesca Sisto2, Francesca Pentimalli5, Anna T Brini2, Augusto Pessina2, Lorenzo Spaggiari6. 1. Department of Thoracic Surgery, European Institute of Oncology, Milan, Italy. Electronic address: francesco.petrella@ieo.it. 2. CRC-StaMeTec, Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy; I.R.C.C.S. Galeazzi Orthopedic Institute, Milan, Italy. 3. Hospital Pharmacy, European Institute of Oncology, Milan, Italy. 4. Department of Cerebrovascular Diseases, Fondazione IRCCS Neurological Institute Carlo Besta, Milan, Italy. 5. Oncology Research Center of Mercogliano (CROM), Istituto Nazionale per Lo Studio E La Cura Dei Tumori "Fondazione Giovanni Pascale", IRCCS, Naples, Italy. 6. Department of Thoracic Surgery, European Institute of Oncology, Milan, Italy; Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy.
Abstract
INTRODUCTION: 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.
INTRODUCTION: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 humanmesothelioma 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.
Authors: Maria Giovanna Scioli; Simona Artuso; Carmen D'Angelo; Manuela Porru; Federico D'Amico; Alessandra Bielli; Pietro Gentile; Valerio Cervelli; Carlo Leonetti; Augusto Orlandi Journal: PLoS One Date: 2018-09-07 Impact factor: 3.240
Authors: Lan G Coffman; Alexander T Pearson; Leonard G Frisbie; Zachary Freeman; Elizabeth Christie; David D Bowtell; Ronald J Buckanovich Journal: Stem Cells Date: 2018-11-02 Impact factor: 6.277