Safety and efficacy of therapeutic angiogenesis as a novel treatment in patients with critical limb ischemia.

Background: In some patients with critical limb ischemia (CLI) the possibility of revascularizing treatment does not exist. In this case therapeutic angiogenesis (TA) using autologous endothelial progenitor cell (EPC) transplantation could be an alternative. The objective of our study was to evaluate the safety and efficacy of TA using EPC.

Methods: Twenty-eight patients with CLI who were not candidates for surgical or endovascular revascularization were included in a prospective study. To mobilize EPCs from the bone marrow, granulocyte colony-stimulating growth factor was injected subcutaneously at doses of 5 microg/kg/day for 5 days. Apheresis was performed, obtaining 50 mL of blood with a high rate of EPCs (CD34(+) and CD133(+) cells were counted). EPCs were implanted in the ischemic limb by intramuscular injections. Primary end points were the safety and feasibility of the procedure and limb salvage rate for amputation at 12 months. Other variables studied were improvement in rest pain, healing of ulcers, ankle-brachial pressure index (ABI), and digital plethysmography. All procedures were done pretreatment and every 3 months for a year on average. Postransplantation arteriography was done in selected cases.

Results: No adverse effects were observed. Mean follow-up was 14 months. Before treatment, mean basal ABI was 0.35+/-0.2 and at 18 months postimplantation, 0.72+/-0.51 (p=0.009). There was a mean decrease of five points in pain scale: basal 8.7+/-1, after TA 3.8+/-2.9 (p=0.01). Seven patients required major amputation. Kaplan-Meier analysis revealed a limb salvage rate of 74.4% after 1 year.

Conclusion: Implantation of EPCs in CLI is a safe alternative, improves tissue perfusion, and obtains high amputation-free rates. Nevertheless, this is a small cohort and results should be tested with long randomized trials.