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

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 x 10(9) +/- 0.3 x 10(9). The number of CD34(+) cells included in the implanted BM-MNCs was 3.8 x 10(7) +/- 1.6 x 10(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. Conclusions - These findings suggest that BM-MNC implantation augments endothelium-dependent vasodilation in patients with limb ischemia.