In vitro anti-myeloma activity of TRAIL-expressing adipose-derived mesenchymal stem cells.

Recently, genetically modified mesenchymal stem cells (MSCs) have beenexploited to deliver anti-cancer bio-drugs directly within the tumour mass.Here, we explored whether adipose-derived MSCs (AD-MSCs), engineeredto express the pro-apoptotic ligand TRAIL (also known as TNFSF10), killmultiple myeloma (MM) cells and migrate toward MM cells in vitro. DifferentMM cell lines were assessed for their sensitivity to recombinanthuman (rh) TRAIL alone and in combination with the proteasome inhibitorbortezomib, which was shown to enhance the effect of rhTRAIL.TRAIL+-AD-MSCs were co-cultured with bortezomib-pretreated MM cellsand their killing activity was evaluated in presence or absence of caspaseinhibition, whereas AD-MSC migration toward media conditioned by bothmyeloma cells and myeloma bone fragments was also investigated. Despitemoderate MM cell sensitivity to rhTRAIL, TRAIL+-AD-MSCs in combinationwith bortezomib significantly induced myeloma cell death. This effectwas associated with caspase-8 activation and abrogated by capsase inhibition.On the other hand, co-culture experiments were performed to evaluatewhether unmodified AD-MSCs affect myeloma cell growth in vitro.AD-MSCs appeared ineffective on myeloma cell growth and showed powerfulmigratory capacity toward MM cells in vitro. These data emphasize theanti-myeloma activity of TRAIL-engineered AD-MSCs and provide supportfor a future model of a cell-based approach against MM.