Therapeutic potential of bone marrow-derived mesenchymal stem cells producing pigment epithelium-derived factor in lung carcinoma.

Specific and efficient gene delivery to target cells and the subsequent expression of the RNA and protein is crucial to the success of gene-based therapy for cancer. Mesenchymal stem cells (MSCs) represent novel and efficient tools for delivery of therapeutic agents to tumor cells. In this study, we evaluated the potential of bone marrow-derived mesenchymal stem cells, genetically modified to express pigment epithelium-derived factor (PEDF) for the treatment of Lewis lung carcinoma (LLC). MSCs derived from murine bone marrow were efficiently engineered to express human PEDF by adenoviral transduction, and the expression and bioactivity of the transgenic protein from engineered MSCs were confirmed in vitro. Animal experiments showed that the systemic administration of MSCs treated with PEDF dramatically reduced the growth of LLC tumors and significantly prolonged survival. Immunohistochemistry analysis of the tumors from MSC-PEDF-treated animals indicated an increase in apoptosis and a decrease in microvessel density. ELISA showed that the group of MSCs treated with PEDF had relatively higher expression levels of PEDF in tumor tissue and lower levels in serum compared with the free Ad-PEDF group. These results suggest that MSCs have potential use as effective delivery of vehicles for therapeutic genes in the treatment of LLC.