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

作　　者：ZHONGZhao-dong ZOUPing HUXian-shi YOUYong CHENZhi-chao HUANGShi-ang 

机构地区：[1]InstituteofHematology,UnionHospital,TongjiMedicalCollege,HuazhongUniversityofScienceandTechnology,Wuhan430022,China

出　　处：《Chinese Medical Journal》2005年第4期289-295,共7页中华医学杂志（英文版）

基　　金：ThisstudywassupportedbyagrantfromtheOverseaOutstandingYoungScholarAwardoftheNationalNaturalScienceFoundationofChina(No 39928010)

摘　　要：Background Bone marrow transplantation ( BMT) conditioning procedure isconsidered as the cause of damage to bone marrow microvasculature and the delay of hematopoiesisrecovery. 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 VEGFgene transfer on preventing damages to bone marrow microenvironment and its promotion ofhematopoiesis in post-BMT mice. Methods Recombinant adenovirus (Ad)-enhanced green fluorescentprotein (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 hVEGFwere 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 marrowmicrovasculature surface area and cellularity. Results Significant expression of EGFP and hVEGF wasobserved 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 recombinantadenovirus 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 microvasculaturesurface 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 atthe 20th and 30th days post BMT [(46.5 ± 5.0)% and (55.1 ± 4.5)%] exceeded those of other BMTgroups (P < 0. 05, respectively). Conclusion VEGF genBackground Bone marrow transplantation ( BMT) conditioning procedure isconsidered as the cause of damage to bone marrow microvasculature and the delay of hematopoiesisrecovery. 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 VEGFgene transfer on preventing damages to bone marrow microenvironment and its promotion ofhematopoiesis in post-BMT mice. Methods Recombinant adenovirus (Ad)-enhanced green fluorescentprotein (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 hVEGFwere 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 marrowmicrovasculature surface area and cellularity. Results Significant expression of EGFP and hVEGF wasobserved 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 recombinantadenovirus 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 microvasculaturesurface 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 atthe 20th and 30th days post BMT [(46.5 ± 5.0)% and (55.1 ± 4.5)%] exceeded those of other BMTgroups (P < 0. 05, respectively). Conclusion VEGF gen

关 键 词：vascular endothelial growth factor gene transfer bone marrowtranspbntation reconstitution of hematopoiesis 

分 类 号：R457.7[医药卫生—治疗学]