Transplantation of autologous bone marrow mononuclear cells with VEGF gene improves diabetic critical limb ischaemia.

Introduction: The aim of this study was to assess the safety and efficacy of combined autologous bone marrow mononuclear cell and VEGF165 gene therapy in patients with diabetes mellitus suffering from critical limb ischaemia (CLI).

Material And Methods: The administration of mononuclear cells (MNCs) and naked VEGF165 plasmid was performed in 16 limbs of 16 patients with rest pain and ischaemic ulcers due to diabetes. MNCs and plasmid were injected into the muscles of the ischaemic limbs. The levels of VEGF in serum and the ankle-brachial index (ABI) were measured before and after treatment. The Visual Analogue Scale (VAS) was used to evaluate pain sensation. CT angiography was performed before and after three months of therapy.

Results: Mean (± SD) plasma levels of VEGF increased non-significantly from 257 ± 80 pg/L to 391 ± 82 pg/L (p 〉 0.05) two weeks after therapy. The ABI improved significantly from 0.26 ± 0.22 to 0.49 ± 0.30 (p 〈 0.001) three months after therapy. A decrease in rest pain was observed in all patients; mean VAS decreased from 6.3 ± 1.4 to 1.2 ± 1.1 after three months (p 〈 0.002). Angiograms showed the development of collateral vessels in 12 limbs. Ischaemic ulcers healed in 12 limbs. Amputation was performed in four patients only, because of advanced wound infection. However, the level of amputations was lowered below knee level in these cases. Complications were limited to transient leg oedema in two patients and fever in two patients.

Conclusions: Intramuscular bone marrow MNCs autotransplantation combined with the administration of phVEGF165 gene is safe, feasible and effective for patients with diabetes and CLI.