IFNalpha-producing bone marrow mesenchymal stem cells (BM-MSCs) contrast tumor growth in a mouse myeloma model.

MSCs are non-hematopoietic progenitor cells with multilineage differentiation potential. Exogenously administered MSCs have been shown to preferentially survive and proliferate in the presence of malignant cells, becoming stromal cells and supporting tumor growth. Thus, MSCs are attractive candidates to deliver biologically active molecules in the tumor environment in vivo and to enhance specific immune responses. IFNα has been used for years in the maintenance therapy of multiple myeloma, increasing both progression-free and overall survival. We analysed the effects of BM-MSCs transduced with mouse IFNα (MSCs/IFNα) in vivo on mice injected subcutaneously with a plasmacytoma-derived tumor (Sp6). BM-MSCs resulted capable of homing into the subcutaneous Sp6 tumor, forming small clusters of cells scattered throughout the tumor and EGFP-positive vessels. Co-injection of MSCs/IFNα with Sp6 resulted in a statistically significant delay in the onset of palpable tumors (tumor incidence of 25% at day 50, whereas myeloma cells alone or coinjected with wild type MSCs showed tumor incidence of 100% 10-15 days after injection). Weekly delivery of MSCs/IFNα (up to 8 total doses) induced a statistically significant decrease of tumor development (tumor incidence: 20% at day 50). The analysis of vascularization suggests a statistically significant reduction of vessel density in tumors treated with MSCs/IFN-α compared with controls. In Conclusion, inhibition of local angiogenesis may be one of the mechanisms of the observed antitumor effect of IFN-α gene therapy in this model. IFN-α is a potent cytokine with impressive therapeutic activity in many tumor models, but the side effects linked to its systemic administration limit its clinical application. The use of MSCs/IFN-α could be a potential way to by-pass this limitation and achieve long-term production of IFN-α only in the tumor microenvironment