Mesenchymal stem cells (MSCs) are adherent, multipotent, non-hematopoietic progenitor cells, which have multilineage differentiation potential. Exogenously administered MSCs have been shown to poorly engraft in rodent adult healthy tissues, although they preferentially survive and proliferate in the presence of malignant cells and become stromal fibroblasts supporting tumor cell growth. Thus MSCs are attractive candidates to deliver genes of immunologically active molecules to the tumor environment in vivo and to enhance specific immune responses. IFNα has been used for the last 20 years in the maintenance therapy of multiple myeloma and it increases both progression-free and overall survival in those patient that tolerate IFNα maintenance therapy and when transplantation is not possible. We have transduced MSCs derived from the bone marrow of Balb/c mice with lentiviral-derived vectors to express mouse IFNα (MSCs/IFNα) and analyzed their effect on subcutaneous tumor growth in vivo, in a plasmacytoma-derived mouse tumor model. The results can be summarized as follows: 1. coinjection of MSCs/IFNα with myeloma cells 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); 2. weekly delivery of MSCs/IFNα induced a statistically significant decrease of tumor development (tumor incidence: 20% at day 50); 3. myeloma cells transduced with IFNα showed in vivo tumor growth rates faster than those of wild type myeloma co-injected with MSC/IFNα, in a statistically significant manner (tumor incidence of 70% at day 50). These results indicate that MSCs secreting IFNα can be useful tools for IFNα gene therapy of tumors.
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