Effects of adenovirus mediated vascular endothelial growth factor gene transfer on reconstitution of hematopoiesis in post-bone marrow transplantation mice

摘要

Background Bone marrow transplantation ( BMT) conditioning procedure is considered as the cause of damage to bone marrow microvasculature and the delay of hematopoiesis recovery. However, hematopoiesis regulation post BMT by vascular endothelial growth factor ( VEGF) has not yet been studied. In this study, adenovirus were used to investigate the effects of VEGF gene transfer on preventing damages to bone marrow microenvironment and its promotion of hematopoiesis in post-BMT mice. Methods Recombinant adenovirus (Ad)-enhanced green fluorescent protein (EGFP)/hVEGF_(165) was injected via tail vein into BALB/c mice undergoing syngeneic BMT. During the different phases post BMT, the distribution of adenovirus and the plasma levels of hVEGF were measured as well as the numbers of white blood cells (WBC) , platelet (PLT) and red blood cells (RBC) in peripheral blood. At the same time, the mice were injected with Chinese ink via tail vein, following which the tibias were separated and were used for analysis of bone marrow microvasculature surface area and cellularity. Results Significant expression of EGFP and hVEGF was observed in multiple organs at different phases post BMT, and the plasma level of hVEGF was up to (866. 67 ± 97. 13 ) pg/ml. The recovery of WBC, PLT and RBC of the group treated with recombinant adenovirus Ad-EGFP/hVEGF_(165) were significantly more rapid than those of other BMT groups (P < 0.05 , respectively). At the 20th day post BMT, the percentage of bone marrow microvasculature surface area in group treated with VEGF [ (61.2 ± 4.0)% ] returned to normal level [ (62.0 ± 5. 0) % , P > 0. 05 ]. The restoration of hematopoiesis was retarded more than that of microvasculature. The cellularity of bone marrow in each group was still lower than that of normal control [ ( 62. 3 ± 4. 0 ) % , P < 0. 05 ] at the 30th day post BMT, but the percentage in group treated with VEGF at the 20th and 30th days post BMT [(46.5 ± 5.0)% and (55.1 ± 4.5)%] exceeded those of other BMT groups (P < 0. 05, respectively). Conclusion VEGF gene transfer mediated by adenovirus may protect the hematopoietic microenvironment to promote the restoration of hematopoiesis in post-BMT mice.