Introduction: Cell-based therapy represents a new frontier in the treatment of a wide variety of human diseases\r\ntraditionally associated with morbidity outcomes, including those involving inflammation, autoimmunity, tissue\r\ndamage, and cancer. However, the use of mesenchymal stem cells (MSCs) to treat multiple myeloma (MM) bone\r\ndisease has raised concerns. Specifically, evidence has shown that infused MSCs might support tumor growth and\r\nmetastasis.\r\nMethods: In this study, we used a standard disseminated MM model in mice to identify the in vivo effects of\r\nintravenous MSC infusion. In addition, a series of in vitro co-culture assays were preformed to explore whether\r\nFas/Fas ligand (Fas-L) is involved in the inhibitory effects of MSCs on MM cells.\r\nResults: In the MM mouse model, treatment of MSCs with highly expressed Fas ligand (Fas-Lhigh MSCs) showed\r\nremarkable inhibitory effects on MM indenization in terms of extending the mouse survival rate and inhibiting\r\ntumor growth, bone resorption in the lumbus and collum femoris, and MM cell metastasis in the lungs and kidneys.\r\nIn addition, reduced proliferation and increased apoptosis of MM cells was observed when co-cultured with\r\nFas-Lhigh MSCs in vitro. Furthermore, mechanistically, the binding between Fas and Fas-L significantly induced\r\napoptosis in MM cells, as evidenced through an increase in the expression of apoptosis marker and Fas in MM cells.\r\nIn contrast, Fas-Lnull MSCs promote MM growth.\r\nConclusions: These data suggest that Fas/Fas-L-induced MM apoptosis plays a crucial role in the MSC-based\r\ninhibition of MM growth. Although whether MSCs inhibit or promote cancer growth remains controversial, the\r\nlevels of Fas-L expression in MSCs determine, at least partially, the effects of MSCs on MM cell growth.
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