The aim: The paper presents the results of our hybrid gene-cell therapy in case of critical lower limb ischemia. Eighteen patients with critical limb ischemia were enrolled to the study. The bone marrow from each patient was harvested. It had been incubated with VEGF165 gene plasmid for two hours before it was administrated intramuscularly into patient's lower limb.
Methods: In the study we evaluated: safety, clinical outcomes of the therapy, venous blood VEGF protein concentration before and after (at: 7th, 14th, 28th and 90th day) administration of the stem cells. We obtained samples of muscles from the patients who underwent the limb amputation, which were examined histological and by PCR (Polymerase Chain Reaction) for detection of plasmid genes.
Results: We observed very good clinical outcomes of the therapy. In ten of eighteen patients (-55%) critical lower limb ischemia symptoms subsided--they saved their limbs. The serum VEGF concentration was higher than in healthy controls (p < 0.05). We observed the increase of the concentration of the cytokine at the 14th day an decrease at the 90th day after administration of cells with plasmid. We found expression of plasmid VEGF in transfected stem cells and in tissues taken from amputated limbs. However histological examination did not reveal any sings of new blood vessels formation in the samples taken from ischemic limbs.
Conclusions: The therapy is safe and effective. We observed significant improvement in patient's clinical state. The therapy needs further investigations.