Arianna Bonomi1, Valeria Sordi2, Erica Dugnani2, Valentina Ceserani3, Marta Dossena3, Valentina Coccè1, Loredana Cavicchini1, Emilio Ciusani4, Gianpietro Bondiolotti5, Giovanna Piovani6, Luisa Pascucci7, Francesca Sisto1, Giulio Alessandri3, Lorenzo Piemonti2, Eugenio Parati3, Augusto Pessina8. 1. Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy. 2. Diabetes Research Institute, IRCCS S. Raffaele Scientific Institute, Milan, Italy. 3. Cellular Neurobiology Laboratory, Department of Cerebrovascular Diseases, IRCCS Neurological Institute C. Besta, Milan, Italy. 4. Laboratory of Clinical Pathology and Neurogenetic Medicine, Fondazione IRCCS Neurological Institute Carlo Besta, Milan, Italy. 5. Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy. 6. Biology and Genetics Division, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. 7. Department of Veterinary Medicine, University of Perugia, Perugia, Italy. 8. Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy. Electronic address: augusto.pessina@unimi.it.
Abstract
BACKGROUND AIMS: Pancreatic cancer (pCa) is a tumor characterized by a fibrotic state and associated with a poor prognosis. The observation that mesenchymal stromal cells (MSCs) migrate toward inflammatory micro-environments and engraft into tumor stroma after systemic administration suggested new therapeutic approaches with the use of engineered MSCs to deliver and produce anti-cancer molecules directly within the tumor. Previously, we demonstrated that without any genetic modifications, MSCs are able to deliver anti-cancer drugs. MSCs loaded with paclitaxel by exposure to high concentrations release the drug both in vitro and in vivo, inhibiting tumor proliferation. On the basis of these observations, we evaluated the ability of MSCs (from bone marrow and pancreas) to uptake and release gemcitabine (GCB), a drug widely used in pCa treatment. METHODS: MSCs were primed by 24-h exposure to 2000 ng/mL of GCB. The anti-tumor potential of primed MSCs was then investigated by in vitro anti-proliferation assays with the use of CFPAC-1, a pancreatic tumor cell line sensitive to GCB. The uptake/release ability was confirmed by means of high-performance liquid chromatography analysis. A cell-cycle study and secretome evaluation were also conducted to better understand the characteristics of primed MSCs. RESULTS: GCB-releasing MSCs inhibit the growth of a human pCa cell line in vitro. CONCLUSIONS: The use of MSCs as a "trojan horse" can open the way to a new pCa therapeutic approach; GCB-loaded MSCs that integrate into the tumor mass could deliver much higher concentrations of the drug in situ than can be achieved by intravenous injection.
BACKGROUND AIMS: Pancreatic cancer (pCa) is a tumor characterized by a fibrotic state and associated with a poor prognosis. The observation that mesenchymal stromal cells (MSCs) migrate toward inflammatory micro-environments and engraft into tumor stroma after systemic administration suggested new therapeutic approaches with the use of engineered MSCs to deliver and produce anti-cancer molecules directly within the tumor. Previously, we demonstrated that without any genetic modifications, MSCs are able to deliver anti-cancer drugs. MSCs loaded with paclitaxel by exposure to high concentrations release the drug both in vitro and in vivo, inhibiting tumor proliferation. On the basis of these observations, we evaluated the ability of MSCs (from bone marrow and pancreas) to uptake and release gemcitabine (GCB), a drug widely used in pCa treatment. METHODS: MSCs were primed by 24-h exposure to 2000 ng/mL of GCB. The anti-tumor potential of primed MSCs was then investigated by in vitro anti-proliferation assays with the use of CFPAC-1, a pancreatic tumor cell line sensitive to GCB. The uptake/release ability was confirmed by means of high-performance liquid chromatography analysis. A cell-cycle study and secretome evaluation were also conducted to better understand the characteristics of primed MSCs. RESULTS:GCB-releasing MSCs inhibit the growth of a human pCa cell line in vitro. CONCLUSIONS: The use of MSCs as a "trojan horse" can open the way to a new pCa therapeutic approach; GCB-loaded MSCs that integrate into the tumor mass could deliver much higher concentrations of the drug in situ than can be achieved by intravenous injection.
Authors: Clara S Mundry; Kirsten C Eberle; Pankaj K Singh; Michael A Hollingsworth; Kamiya Mehla Journal: Biochim Biophys Acta Rev Cancer Date: 2020-06-21 Impact factor: 10.680
Authors: Adam Nowakowski; Katarzyna Drela; Justyna Rozycka; Miroslaw Janowski; Barbara Lukomska Journal: Stem Cells Dev Date: 2016-09-07 Impact factor: 3.272