Murine bone marrow stromal cells: implications for their use in gene modified cell therapy.

The objectives of this study were to demonstrate that bone marrow stromal cells (BMSC) can be an attractive novel target of genetic modification in gene and cell therapy of hematologic disease. Here, we investigated the therapeutic effects of gene modified BMSC using a murine lymphoma model. BMSC of Balb/c AnN mice were encoded with the human IL-2 gene (hIL-2) using an adenoviral vector. About 1 x 10(6) cells of a murine B lymphoma (A20) cell line, were injected into the mice via tail vein. One week after injection of A20 cells, the mice were divided into 4 groups for BMSC therapy: No BMSC (control), unmodified BMSC, BMSC with Ad/deltaE1, and BMSC with Ad/hIL-2. Mice were observed for 8 weeks. The results demonstrated that all mice treated with BMSC (Ad/hIL-2) survived with no evidence of disease during this period of observation. All mice treated with unmodified BMSC or BMSC (Ad/deltaE1) as well as the controls developed disseminated lymphoma, and 80% of mice survived less than 4 weeks. In conclusion, the IL-2 gene-modified stromal cell is a promising therapeutic tool for murine lymphoma.