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  • Walter, Dirk H; Krankenberg, Hans; Balzer, Jörn O; Kalka, Christoph; Baumgartner, Iris; Schlüter, Michael; Tonn, Torsten; Seeger, Florian; Dimmeler, Stefanie; Lindhoff-Last, Edelgard; Zeiher, Andreas M

    Circulation. Cardiovascular interventions, 2011-February, Letnik: 4, Številka: 1
    Journal Article

    Critical limb ischemia due to peripheral arterial occlusive disease is associated with a severely increased morbidity and mortality. There is no effective pharmacological therapy available. Injection of autologous bone marrow-derived mononuclear cells (BM-MNC) is a promising therapeutic option in patients with critical limb ischemia, but double-blind, randomized trials are lacking. Forty patients with critical limb ischemia were included in a multicenter, phase II, double-blind, randomized-start trial to receive either intraarterial administration of BM-MNC or placebo followed by active treatment with BM-MNC (open label) after 3 months. Intraarterial administration of BM-MNC did not significantly increase ankle-brachial index and, thus, the trial missed its primary end point. However, cell therapy was associated with significantly improved ulcer healing (ulcer area, 3.2±4.7 cm(2) to 1.89±3.5 cm(2) P=0.014 versus placebo, 2.92±3.5 cm(2) to 2.89±4.1 cm(2) P=0.5) and reduced rest pain (5.2±1.8 to 2.2±1.3 P=0.009 versus placebo, 4.5±2.4 to 3.9±2.6 P=0.3) within 3 months. Limb salvage and amputation-free survival rates did not differ between the groups. Repeated BM-MNC administration and higher BM-MNC numbers and functionality were the only independent predictors of improved ulcer healing. Ulcer healing induced by repeated BM-MNC administration significantly correlated with limb salvage (r=0.8; P<0.001). Intraarterial administration of BM-MNC is safe and feasible and accelerates wound healing in patients without extensive gangrene and impending amputation. These exploratory findings of this pilot trial need to be confirmed in a larger randomized trial in patients with critical limb ischemia and stable ulcers.