The improving effect of gene engineered bone marrow stromal cell line which can induce IL-2 gene expression on immune reconstitution after bone marrow transplantation
Objective To study the potential effect of bone marrow stromal cell line QXMSC1 engineered to secrete IL-2 to accelerate the immune reconstitution in allogeneic bone marrow transplantation mice. Methods The regulable recombined retrovirus vector was constructed firstly which contains IL-2 cDNA and then transfected bone marrow stromal cell line, established doxycycline inducible gene expression system on bone marrow stromal cell line QXMSC1tet-on-IL-2 which can induce IL-2 gene expression by Dox. The activity of IL-2 was measured under different Dox concentration. The lethally irradiated mice C57BL/6 (H-2d) were cografted allogeneic bone marrow (BALB/c, H-2d, 1×107/mice) with QXMSC1tet-on-IL-2 (5×105/mice) at same time. Dox was administrated for 15 days to induce the expression of IL-2. Lymphocyte proliferation to Con A, plaque-forming cell (PFC), delayed type hypersensitivity (DTH) frequency of helper T lymphocyte precursor (HTLp) and T cell subset CD4+/CD8+ were examined on the 30, 60 day post transplantation, respectively. Results Firstly, the gene engineered stromal cell line achieves high-level and regulatable IL-2 gene expression. The results showed that lymphocytes proliferation to ConA was increased, frequency of HTLp, the ability of DTH and PFC was improved by coinfused stromal cells QXMSC1tet-on-IL-2 on the 30, 60 day after bone marrow transplantation. Conclusion These data demonstrated that the gene engineered bone marrow stromal cell line (QXMSC1tet-on-IL-2) could improve the immune reconstitution in allogeneic bone marrow transplantation.