The Combined Delivery of the Vegf , Ang , and Gdnf Genes Stimulates Angiogenesis and Improves Post-Ischemic Innervation and Regeneration in Skeletal Muscle

In this study, the effects of different combinations of the genes , , and injected both using direct virus-mediated injection (adenovirus, Ad5) and umbilical cord blood mononuclear cells (UCBCs) on the processes of stimulation of post-ischemic innervation, angiogenesis, and regeneration in skeletal muscle were investigated in a rat hindlimb chronic ischemia model. It was shown that more pronounced stimulation of angiogenesis and restoration of post-ischemic innervation were achieved both in the early (28 days post-ischemia, dpi) and late (42 dpi) terms of the experiment in the calf muscle when UCBCs delivered the combination of Ad5- and Ad5- compared to the direct injection of the same vector combination into the area of ischemia. At the same time, the inclusion of Ad5- in the combination of Ad5- and Ad5- directly injected or administered by UCBCs provided a significant increase in the number of centronuclear muscle fibers, indicating stimulation of post-ischemic reparative myogenesis. This study allowed us to determine the most effective gene combinations for angiogenesis and neurogenesis, which, in the future, may serve as the basis for the development of gene and gene cell products for the treatment of chronic lower limb ischemia.