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Bone marrow-derived mesenchymal stem cells (MSC) are multipotent adult stem cells of mesodermal origin localized within the bone marrow compartment. MSC possess multilineage property making them useful for a number of potential therapeutic applications. MSC can be isolated from the bone marrow, expanded in culture and genetically modified to serve as cell carriers for local or systemic therapy. Despite their ability to differentiate into osteoblasts, chondrocytes, adipocytes, myocytes and neuronal cells under appropriate stimuli, distinct molecular signals that guide migration of MSC to specific targets largely remain unknown. The pluripotent nature of MSC makes them ideal resources for regenerative medicine, graft-versus-host disease and autoimmune diseases. Despite their therapeutic potential in a variety of diseases, certain issues need to be critically addressed both in in vitro expansion of these cells without losing their stem cell properties, and the long-term fate of the transplanted MSC in vivo following ex vivo modifications. Finally, understanding of complex, multistep and multifactorial differentiation pathways from pluripotent stem cells to functional tissues will allow us to manipulate MSC for the formation of competent composite tissues in situ. The present article will provide comprehensive account of the characteristics of MSC, their isolation and culturing, multilineage properties and potential therapeutic applications.

Cell-based therapy for cancer is a promising new field. Among cell types that can be used for this purpose, mesenchymal stem cells (MSCs) appear to hold great advantage for reasons including easier propagation in culture, possible genetic modification to express therapeutic proteins and preferential homing to sites of cancer growth upon in vivo transfer. The present study evaluated the potential of genetically modified MSC, constitutively expressing interferon (IFN)-beta, in an immunocompetent mouse model of prostate cancer lung metastasis. A recombinant adeno-associated virus (rAAV) encoding mouse IFN-beta was constructed and initially tested in vitro for high-level expression and bioactivity of the transgenic protein. MSCs were transduced by the rAAV-IFN-beta or green fluorescent protein ex vivo and used as cellular vehicles to target lung metastasis of TRAMP-C2 prostate cancer cells in a therapy model. Cohorts of mice were killed on days 30 and 75 to determine the effect of therapy by measurement of tumor volume, histology, immunohistochemistry, enzyme-linked immunosorbent assay and flow cytometry. Results indicated a significant reduction in tumor volume in lungs following IFN-beta-expressing MSC therapy. Immunohistochemistry of the lung demonstrated increased tumor cell apoptosis and decreased tumor cell proliferation and blood vessel counts. A significant increase in the natural kill cell activity was observed following IFN-beta therapy correlating the antitumor effect. Systemic level of IFN-beta was not significantly elevated from this targeted cell therapy. These data demonstrate the potential of MSC-based IFN-beta therapy for prostate cancer lung metastasis.