Effects of direct and indirect delivery of the VEGF gene by cord blood cells in limb ischemia area in rats

The effects of delivery of recombinant human VEGF165 gene under conditions of direct and cell-mediated gene therapy were studied in the model of posterior limb ischemia. Immediately after the creation of the ischemia model, a solution with the VEGF gene (Ad-VEGF group) or the mononuclear blood cells of the human umbilical cord (PCC) mononuclear cells (group CCP + Ad-VEGF) transduced by the same gene was injected into the distal part of the gastrocnemius muscle. At day 14, an increase in the number of CD31- and CD34-immunopositive cells in the ischemic gastrocnemius muscle was shown in both groups of animals. The number of CD31- and CD34-immunopositive cells in the Ad-VEGF group increased by 23% and by 2 times, respectively, and by 4 and 5 times, respectively, in the CKP + Ad-VEGF group. At this time, the number of CD31-immunopositive cells in the CKP + Ad-VEGF group was greater by a factor of 3, and the CD34-immunopositive cells by a factor of 2 compared with the Ad-VEGF group. A significantly larger increase in the number of endothelial cells, when delivered to the ischemia region of the VEGF gene by PPC compared to direct injection of the gene into the same region, indicates a significantly higher efficiency of angiogenesis under conditions of cell-mediated gene therapy.