Authors: Yong Zhang Chaohua Guo Hongbin Zhang Shiwu Dong
Publish Date: 2009/06/16
Volume: 90, Issue: 1, Pages: 64-73
Abstract
The objective of the present work was to study the effect of interleukin3 IL3 and Flt3 ligand FL overexpression in human cord blood CD34+ cells on rescuing lethally irradiated mice by transplantation CD34+ cells were isolated from human umbilical cord blood UCB and infected with recombinant retrovirus expressing FL IL3 or FL/IL3 genes respectively Stably transduced CD34+ cells were transplanted iv into NOD/SCID/IL2rγnull mice that had been conditioned with 80 Gy of irradiation At 6 weeks postirradiation chimerism in the animal bone marrow BM and the spleen were investigated Recovery of peripheral blood cell and animal survival were recorded 2 4 and 6 weeks postirradiation The chimerism was further investigated by serial transplantation assay At 6 weeks posttransplantation each of the three transduced human UCB CD34+ cell types could be observed in all examined BM of chimeric mice however more human cells could be found in BM spleen and peripheral blood of those mice transplanted with CD34+ cells overexpressing IL3/FL cells Overexpression of IL3 and FL at mRNA and protein levels could be detected in the BM cells of chimeric mice Accordingly hIL3/FL cooverexpressing mice showed greater recovery of peripheral blood counts as early as 2 weeks after irradiation and a much higher survival rate 11/12 than other groups at 6 weeks postirradiation Serial transplantation assay indicated that human cord blood CD34+ cells could recover potentials of proliferation and selfrenewal after being transplanted into mice Our results suggested that transplant of CD34+ cord blood cells overexpressing IL3/FL genes improved rescue of radiationinjured mice which probably results from the synergistic effect between hIL3 and hFL causing the rapid reconstitution of hematopoiesis
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