Therapeutic Angiogenesis Using Bone Marrow-Derived Mononuclear Cell Implantation for Patients With Critical Limb-Threatening Ischemia Caused by Thromboangiitis Obliterans　― Study Protocol for a Multicenter Prospective Interventional Trial ―

Background: Patients with thromboangiitis obliterans (TAO) can develop critical limb-threatening ischemia (CLTI) and require limb amputation. Smoking cessation and exercise therapy are recommended as standard treatments, and revascularization by bypass surgery or endovascular therapy (EVT) is required for patients with CLTI. However, there are many cases in which revascularization is difficult because of vascular characteristics, and the patency rate after revascularization remains unsatisfactory. Therapeutic angiogenesis using bone marrow-derived mononuclear cell (BM-MNC) implantation is used clinically, with many trials demonstrating long-term efficacy and safety of the technique in patients with CLTI, especially that caused by TAO. To expand the use of BM-MNCs implantation in clinical practice, further evidence is required in patients with CLTI caused by TAO. Methods and Results: This trial is a multicenter, prospective, non-randomized interventional trial of an Advanced Medicine B treatment approach. We aim to enroll 25 patients aged 20–80 years with Fontaine classification Stage III or IV, who will undergo BM-MNC implantation. The primary endpoint is the improvement in skin perfusion pressure of the target limb 180 days after BM-MNC implantation, whereas secondary endpoints are improvements in rest pain or ulcer size. We will also investigate rates of major or minor amputation, survival, and adverse events during follow-up. Conclusions: BM-MNC implantation is expected to be an efficacious and feasible treatment for patients with CLTI caused by TAO.