Therapeutic angiogenesis for peripheral artery diseases by autologous bone marrow cell transplantation

Critical limb ischemia (CLI) is a terminal stage of peripheral artery disease (PAD). The number of patients with CLI is increasing, and the disease has a major impact on patients' quality of life. In spite of the marked advances in surgery and interventional angioplasty, a large number of patients require revascularization. To treat these patients, cell based angiogenesis is attracting a great deal of attention as a new strategy. "Therapeutic angiogenesis" is a term that has become widely used in the last decade. Despite negative results in several clinical trials of cytokine-based angiogenesis, cell based therapy produced effective angiogenesis. This cell-based angiogenesis originates from persistent basic research. The first clinical randomized pilot study was reported in 2002. Up to now, more than 30 clinical studies on the use of mononuclear cells or progenitor cells for the treatment have been published. As the prognosis of the patients with CLI is poor, it has been discussed with respect to their safety and feasibility. With the increasing number of treated patients, the accumulated outcomes from these clinical studies are demonstrating this therapy to be reliable. They reveal indications of the stage of the patients with PAD and the timing of treatments. However, clinical data concerning long time prognosis and a standardized protocol have not been discussed sufficiently. This review summarises data from recent clinical outcomes from 17 studies (11 involving BMMNC that included >10 patients, 6 involving PBMNC that included >10 patients) that are treating patients with PAD by autologous cell transplantation.