Therapeutical potential of blood-derived progenitor cells in patients with peripheral arterial occlusive disease and critical limb ischaemia

Abstract

Despite considerable advances in the therapy of patients with peripheral arterial occlusive disease (PAOD) and critical limb ischaemia (CLI), a substantial number remain, in whom amputation has to be considered the only and final option. Recent evidence from animal models of hind limb ischaemia suggests that neovascularization induced by circulating blood-derived progenitor cells (CPCs) may permit limb salvage. It remains unclear, however, whether an intra-arterial application of autologous CPCs in patients with infrapopliteal PAOD and CLI is safe, feasible, and of potentially beneficial effects. Seven patients with critical PAOD were treated with an intra-arterial infusion of autologous CPCs (39+/-24 x 10(6)) isolated from peripheral blood. Pre-interventional stimulation with G-CSF and CPC application was well tolerated. Twelve weeks after CPC administration, the pain-free walking distance increased from 6+/-13 to 195+/-196 m. A significant increase in the ankle-brachial index, transcutaneous O(2), flow-dependent vasodilation, flow reserve in response to adenosine, and endothelium-dependent vasodilation was observed. These preliminary data in a small series of patients with CLI without surgical or interventional options indicate that CPC application is safe, feasible, and may improve both functional and clinical indices.