Interpretation:

Among patients with ischemic limb disease due to peripheral vascular disease, autologous implantation of bone marrow-mononuclear cells was safe and was associated with improvement in ABIs, rest pain, and pain free walking time. These observations are consistent with therapeutic angiogenesis mediated by the ability of bone marrow cells to supply endothelial progenitor cells and to secrete various angiogenic growth factors or cytokines. In this study, bone-marrow implantation was associated with increases in blood flow among patients with critical limb ischemia, as assessed by substantial increases in ABI, TcO2, and pain-free walking time and by formation of new collateral vessel formation on the angiogram. Implantation of bone marrow-mononuclear cells also improved clinical symptoms such as rest pain, and ischemic ulcers or gangrene allowing successful limb salvage. One of the limitations of this study is the relatively short duration of follow-up of 24 weeks, which precludes true assessment of the long-term safety of this approach. The 8 % cardiac mortality in Group A is disconcerting, as angiogenic growth factors may be associated with accelerated atherosclerotic plaque growth. Overall, this small preliminary study is encouraging but requires prospective validation in larger randomized blind trials with a longer duration of follow-up.