Autologous mesenchymal stem cells as a novel therapy for no-option critical limb ischemia: preliminary results of a phase 1 study

Background: Critical limb ischemia (CLI) is the end-stage of peripheral vascular disease, affecting 310% of the population. Surgical or endovascular revascularization is the preferred therapy; however, it is unachievable in 2540% of patients due to comorbidities or anatomically diffused disease. No-option CLI patients are at high risk for amputation and death, representing an unmet medical need. CLI Stem Cells is a phase 1b safety study examining the use of mesenchymal stem cells (MSCs) as a novel therapy to induce angiogenesis for no-option CLI patients. Methods: This is a non-randomized, uncontrolled, open label dose escalation study. Target doses are 20, 40, and 80 million cells with three patients in each group. Eligible patients undergo bone marrow harvest and cell expansion is done in GMP-facility over 68 weeks. Successfully released cells are then injected intramuscularly to the ischemic limb. Results: Five out of eight enrolled patients proceeded to bone marrow harvest and three patients received cell therapy. Forty-five adverse events were recorded and none were related to MSCs therapy. Preliminary efficacy results showed clinically significant decrease in the mean ischemic rest pain from baseline to 30 days after treatment (8 and 2.3 10, respectively). This decrease did not reach statistical significance (p = 0.12). There was no change in ankle brachial index. Complete ulcer healing was observed in one out of the three treated patients. Conclusion: Intramuscular transplantation of 20 million autologous bone marrow MSCs is safe and feasible and may be beneficial in reducing ischemic rest pain and enhance ulcer healing