Treatment of peripheral arterial disease using stem and progenitor cell therapy

Peripheral arterial disease (PAD) is a highly prevalent atherosclerotic syndrome associated with significant morbidity and mortality. PAD is most commonly caused by atherosclerosis obliterans (ASO) and thromboangiitis obliterans (TAO), and can lead to claudication and critical limb ischemia (CLI), often resulting in a need for major amputation and subsequent death. Standard treatment for such severe cases of PAD is surgical or endovascular revascularization. However, up to 30% of patients are not candidates for such interventions, due to high operative risk or unfavorable vascular involvement. Therefore, new strategies are needed to offer these patients a viable therapeutic option. Bone-marrow derived stem and progenitor cells have been identified as a potential new therapeutic option to induce angiogenesis. These findings prompted clinical researchers to explore the feasibility of cell therapies in patients with peripheral and coronary artery disease in several small trials. Clinical benefits were reported from these trials including improvement of ankle-brachial index (ABI), transcutaneous partial pressure of oxygen (TcO2), reduction of pain, and decreased need for amputation. Nonetheless, large randomized, placebo-controlled, double-blind studies are necessary and currently ongoing to provide stronger safety and efficacy data on cell therapy. Current literature is supportive of intramuscular bone marrow cell administration as a relatively safe, feasible, and possibly effective therapy for patients with PAD who are not subjects for conventional revascularization.Clinical RelevanceThis article describes the background and first results of stem and progenitor cell therapy in patients with critical limb ischemia not suitable for revascularization. The principle as far as it is understood and the methods are described. Compelling evidence suggests that progenitor cell therapy might become a useful adjunct to the treatment options at present. Due to poor prognosis and the increasing number of patients, there is a need for new therapeutic methods. The article gives an overview of first encouraging results provided by early-phase clinical trials. Challenges in this new therapeutic option still include open questions such as cell phenotype, processing, dosing, route of optimal delivery, and frequency of application. Validation by more rigorous controlled trials involving homogenous patient populations are required to confirm the first hopeful results.