Safety and efficacy of autologous progenitor cell transplantation for therapeutic angiogenesis in patients with critical limb ischemia.

BACKGROUND: Therapeutic angiogenesis using cell transplantation (TACT) is a treatment strategy for no-option patients with critical limb ischemia (CLI). However, because one-third of treated patients fail to respond, the present study was an exploration of the characteristics of responders and non-responders to this treatment regimen. METHODS AND RESULTS: Seven CLI patients (3 with Buerger's disease, 4 with arteriosclerosis obliterans undergoing chronic hemodialysis (ASO-HD)) were treated according to the TACT protocol (n=6: bone marrow-mononuclear cells (MNCs); n=1: peripheral blood-MNCs). Subjective symptoms (visual analog scale) and objective findings (extent of ulcer, ankle-brachial pressure index, transcutaneous oxygen pressure, thermography and angiography) were assessed. Numbers of transplanted CD34+, CD133+ and CD34+ CD133+ cells were counted. Changes in circulating CD34+ and CD133+ cell numbers were also examined before and after the treatment. All responders (n=3) had Buerger's disease, and ASO-HD patients did not respond well. Among the responders, the numbers of circulating CD34+ and CD133+ cells persistently increased for 1 month after the treatment, but not in non-responders. CONCLUSIONS: The TACT regimen improved CLI in patients with Buerger's disease but not in those with ASO-HD in this small study. In responders, post procedural circulating CD34+ and CD133+ cells persistently increased for 1 month (ClinicalTrials.gov Identifier: NCT00145262, TACT-NAGOYA).