Autologous stem cell therapy for peripheral arterial disease Meta-analysis and systematic review of the literature

BACKGROUND: Peripheral arterial disease (PAD) is a common cause of disability and mortality. Up to one third of patients are not susceptible to traditional revascularization and may benefit from stem cell therapies. OBJECTIVE: In this meta-analysis, we sought to determine whether autologous cell therapy is effective in the treatment of PAD. METHODS: We searched the English literature in Medline, Excerpta Medica and the Cochrane database for trials of autologous cell therapy in patients with PAD published before 31 January 2009. We included controlled and non-controlled, randomized and non-randomized trials using autologous bone marrow or granulocyte colony stimulating factor (G-CSF) mobilized peripheral blood cells to treat PAD. We also collected data from trials of G-CSF monotherapy, as a control treatment. RESULTS: In a meta-analysis of 37 trials, autologous cell therapy was effective in improving surrogate indexes of ischemia, subjective symptoms and hard endpoints (ulcer healing and amputation). On the contrary, G-CSF monotherapy was not associated with significant improvement in the same endpoints. Patients with thromboangiitis obliterans showed some larger benefits than patients with atherosclerotic PAD. The intramuscular route of administration and the use of bone marrow cells seemed somehow more effective than intrarterial administration and the use of mobilized peripheral blood cells. The procedures were well tolerated and generally safe. CONCLUSION: This meta-analysis indicates that intramuscular autologous bone marrow cell therapy is a feasible, relatively safe and potentially effective therapeutic strategy for PAD patients, who are not candidate for traditional revascularization. Larger, placebo-controlled, randomized multicenter trials need to be planned and conducted to confirm these findings.