A randomized, controlled study of autologous therapy with bone marrow-derived aldehyde dehydrogenase bright cells in patients with critical limb ischemia

Objectives: The safety and efficacy of direct intramuscular injections of aldehyde dehydrogenase bright (ALDH ^br) cells isolated from autologous bone marrow mononuclear cells (ABMMNCs) and ABMMNCs were studied in patients with critical limb ischemia (CLI) who were not eligible for percutaneous or surgical revascularization. Background: Many CLI patients are not candidates for current revascularization procedures, and amputation rates are high in these patients. Cell therapy may be a viable option for CLI patients. Methods: Safety was the primary objective and was evaluated by occurrence of adverse events. Efficacy, the secondary objective, was evaluated by assessment of Rutherford category, ankle-brachial index (ABI), transcutaneous partial pressure of oxygen (TcPO ₂), quality of life, and pain. Results: ALDH ^br cells and ABMMNCs were successfully administered to all patients. No therapy-related serious adverse events occurred. Patients treated with ALDH ^br cells (n = 11) showed significant improvements in Rutherford category from baseline to 12 weeks (mean, 4.09 ± 0.30 to 3.46 ± 1.04; P = 0.05) and in ABI at 6 (mean, 0.22 ± 0.19 to 0.30 ± 0.24; P = 0.02), and 12 weeks (mean, 0.36 ± 0.18; P = 0.03) compared with baseline. Patients in the ABMMNC group (n = 10) showed no significant improvements at 6 or 12 weeks in Rutherford category but did show improvement in ABI from baseline to 12 weeks (0.38 ± 0.06 to 0.52 ± 0.16; P = 0.03). No significant changes from baseline were noted in ischemic ulcer grade or TcPO ₂ in either group. Conclusions: Administration of autologous ALDH ^br cells appears to be safe and warrants further study in patients with CLI.