Paclitaxel-releasing mesenchymal stromal cells inhibit the growth of multiple myeloma cells in a dynamic 3D culture system.
Multiple myeloma is an aggressive tumour able to suppress osteoblastogenesis probably mediated by bone marrow mesenchymal stromal cells (BM-MSCs) that can also support plasma cell growth/survival. The use of MSCs for multiple myeloma therapy is a controversial topic because of the contradictory results on the capacity of MSCs to inhibit or to promote cancer growth. Our previous studies demonstrated that MSCs could be loaded with Paclitaxel (PTX) and used to deliver the drug in situ in amount affecting tumour growth (in vitro and in vivo). Therefore, independently on the discussed action of MSCs in myeloma, MSCs could represent a 'trojan horse' to vehicle and deliver anti-tumour agents into bone marrow. This study confirms, by an in vitro 3D dynamic culture system, that PTX loaded BM-MSCs (PTXr-MSCs) are active on the proliferation of RPMI 8226, a human myeloma cell line. Our results demonstrated a dramatic suppression of myeloma cell growth by PTXr-MSCs, suggesting that drug loaded MSCs could be a tool to deliver drug into the bone marrow. Drug releasing MSCs provide a therapeutic approach to potentiate the existing treatments against a very aggressive malignancy as multiple myeloma. Copyright © 2016 John Wiley & Sons, Ltd.
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
Arianna
A
Bonomi
Laboratory of Tissue Engineering, Anatomy and Physiopathology Unit, Department of Clinical and Experimental Sciences, School of Medicine, University of Brescia, Brescia, Italy.
Nathalie
N
Steimberg
Department of Clinical and Experimental Sciences, Institute of Pathological Anatomy, School of Medicine, University of Brescia, Brescia, Italy.
Anna
A
Benetti
Department of Clinical and Experimental Sciences, Institute of Pathological Anatomy, School of Medicine, University of Brescia, Brescia, Italy.
Angiola
A
Berenzi
Cellular Neurobiology Laboratory, Department of Cerebrovascular Diseases, IRCCS Neurological Institute C. Besta, Milan, Italy.
Giulio
G
Alessandri
Department of Veterinary Medicine, University of Perugia, Perugia, Italy.
Luisa
L
Pascucci
Laboratory of Tissue Engineering, Anatomy and Physiopathology Unit, Department of Clinical and Experimental Sciences, School of Medicine, University of Brescia, Brescia, Italy.
Jennifer
J
Boniotti
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
Valentina
V
Coccè
Diabetes Research Institute, IRCCS S. Raffaele Scientific Institute, Milan, Italy.
Valeria
V
Sordi
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
Augusto
A
Pessina
Laboratory of Tissue Engineering, Anatomy and Physiopathology Unit, Department of Clinical and Experimental Sciences, School of Medicine, University of Brescia, Brescia, Italy.
Giovanna
http://orcid.org/0000-0002-9433-1649
G
Mazzoleni
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017077:Culture Media, Conditioned; D019008:Drug Resistance, Neoplasm; D004361:Drug Tolerance; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism*; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology*; D018874:Spheroids, Cellular; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D017077:Culture Media, Conditioned; D017239:Paclitaxel
RPMI 8226 cells; mesenchymal stromal cells (MSCs); multiple myeloma (MM); paclitaxel; rotary cell culture system (RCCS) bioreactor