Autologous stem cell therapy for peripheral arterial disease: Meta-analysis and systematic review of the literature
Received 17 June 2009; received in revised form 5 August 2009; accepted 17 August 2009. published online 10 September 2009.
Abstract
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.
Department of Clinical and Experimental Medicine, University of Padova, Medical School, Padova, Italy
Corresponding author at: Dipartimento di Medicina Clinica e Sperimentale, Divisione di Malattie del Metabolismo, Policlinico Universitario, via Giustiniani, 2, 35100, Padova, Italy. Tel.: +39 049 8212185; fax: +39 049 8212184.
ABSTRACT