Autologous Bone-Marrow Mononuclear Cell Implantation Improves Endothelium-Dependent Vasodilation in Patients With Limb Ischemia

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Abstract
Background— 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. Methods and Results— 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 1.6×109±0.3×109. The number of CD34+ cells included in the implanted BM-MNCs was 3.8×107±1.6×107. 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. Conclusions— These findings suggest that BM-MNC implantation augments endothelium-dependent vasodilation in patients with limb ischemia.