Phase Ib Open Clinical Trial to Assess the Safety of AutologousMesenchymal Stem Cells for the Treatment of NonrevascularizableCritical Lower Limb Ischemia

Abstract

Background: Critical limb ischemia is a highly disabling disease, characterized by chronic pain at rest, ulceration and tissue tropism attributable to arterial occlusion. Despite significant advances in recent years in treating this disease, there are patients who, for technical reasons or because of the benefit/risk balance, have no therapeutic options other than amputation of the affected limb. Objective: This study’s objective was to assess the feasibility and safety of autologous Adipose Tissue-Derived Mesenchymal Stem Cell (AT-MSC) implantation in patients with lower limb ischemia who are not candidates for surgical or endovascular revascularization. Methods: This is a pragmatic, phase Ib, open, one-arm clinical trial, with a 1-year follow-up after cell implantation. The dose was 1 × 106 AT-MSCs/kg. AT-MSCs were diluted into a final volume of 25 mL of Ringer solution and injected as 25 aliquots of 1 mL into each injection site on the limb. Injection sites were selected below the knee at 25 different sites of the ischemic calf muscle along the tibial and peroneal arteries. Liposuction was done in the abdomen. Results: A total of 7 patients underwent treatment for 21 months. Two patients showed no serious complications with the liposuction, only pain and mild infection. No serious cell implantation-related adverse event occurred during the follow-up, although 2 patients had to undergo amputation. The ankle-brachial index and clinical assessment of the limb improved during the follow-up. Conclusion: In conclusion, AT-MSC treatment of critical limb ischemia is feasible, safe and has promising initial results for salvaging limbs in the short term.