Background: Angiogenic cell therapy by intramuscular injection of autologous bone marrow mononuclear cells was first attempted in patients with peripheral artery disease (PAD) with critical limb ischemia, and the feasibility was shown by a randomized controlled Therapeutic Angiogenesis by Cell Transplantation (TACT) study.
Methods and results: The present study was designed to assess the 3-year safety and clinical outcomes of this angiogenic cell therapy by investigating the mortality and leg amputation-free interval as primary end points. The median follow-up time for surviving patients was 25.3 months (range, 0.8-69.0 months), and 3-year overall survival rates were 80% (95% CI 68-91) in patients with atherosclerotic peripheral arterial disease (11 died in 74 patients) and 100% (no death) in 41 patients with thromboangiitis obliterans (TAO; Buerger's disease). Three-year amputation-free rate was 60% (95% CI 46-74) in PAD and 91% (95% CI 82-100) in patients with TAO. The multivariate analysis revealed that the severity of rest pain and repeated experience of bypass surgery were the prognostic factors negatively affecting amputation-free interval. The significant improvement in the leg pain scale, ulcer size, and pain-free walking distance was maintained during at least 2 years after the therapy, although the ankle brachial index and transcutaneous oxygen pressure value did not significantly change.
Conclusions: The angiogenic cell therapy using bone marrow mononuclear cells can induce a long-term improvement in limb ischemia, leading to extension of amputation-free interval. The safety and efficacy are not inferior to the conventional revascularization therapies.