Autologous bone-marrow mononuclear cell implantation improves endothelium-dependent vasodilation in patients with limb ischemia.

Abstract

Patients with limb ischemia were associated with endothelial dysfunction. The purpose of this study was to determine whether autologous bone-marrow mononuclear cell (BM-MNC) implantation improves endothelial dysfunction in patients with limb ischemia. We evaluated the leg blood flow (LBF) response to acetylcholine (ACh), an endothelium-dependent vasodilator, and sodium nitroprusside (SNP), an endothelium-independent vasodilator, before and after BM-MNC implantation in 7 patients with limb ischemia. LBF was measured with a mercury-filled Silastic strain-gauge plethysmograph. The number of BM-MNCs implanted into ischemic limbs was 1.6x10(9)+/-0.3x10(9). The number of CD34+ cells included in the implanted BM-MNCs was 3.8x10(7)+/-1.6x10(7). BM-MNC implantation improved the ankle-brachial pressure index (0.33+/-0.21 to 0.39+/-0.17, P=0.06), transcutaneous oxygen pressure (28.4+/-11.5 to 36.6+/-5.2 mm Hg, P=0.03), and pain-free walking time (0.8+/-0.6 to 2.9+/-2.2 minutes, P=0.02). After BM-MNC implantation, LBF response to ACh was enhanced (19.3+/-6.8 versus 29.6+/-7.1 mL/min per 100 mL; P=0.002). The vasodilatory effect of SNP was similar before and after BM-MNC implantation. These findings suggest that BM-MNC implantation augments endothelium-dependent vasodilation in patients with limb ischemia.