Characteristics of responders to autologous bone marrow cell therapy for no-option critical limb ischemia

Background The present study investigated factors associated with therapeutic benefits after autologous bone marrow cell (BMC) therapy in patients with “no-option” critical limb ischemia (CLI). Methods and results Sixty-two patients with advanced CLI (Rutherford category 5 or 6) not eligible for revascularization were randomized to treatment with 40 ml of autologous BMCs (SmartPreP2) by local intramuscular ( n = 32) or intra-arterial ( n = 30) application. The primary endpoint was limb salvage and wound healing at 12 months. Seven patients (11 %) died during the follow-up from reasons unrelated to stem cell therapy. The BMC product of patients with limb salvage and wound healing (33/55) was characterized by a higher CD34 + cell count ( p = 0.001), as well as a higher number of total bone marrow mononuclear cells (BM-MNCs) ( p = 0.032), than that of nonresponders (22/55). Patients with limb salvage and wound healing were younger ( p = 0.028), had lower C-reactive protein levels ( p = 0.038), and had higher transcutaneous oxygen pressure (tcpO 2 ) ( p = 0.003) before cell application than nonresponders. All patients with major tissue loss at baseline (Rutherford 6 stage of CLI, n = 5) showed progression of limb ischemia and required major limb amputation. In the multiple binary logistic regression model, the number of applied CD34 + cells ( p = 0.046) and baseline tcpO 2 ( p = 0.031) were independent predictors of limb salvage and wound healing. The number of administrated BM-MNCs strongly correlated with decreased peripheral leukocyte count after 6 months in surviving patients with limb salvage ( p = 0.0008). Conclusion Patients who benefited from autologous BMC therapy for “no-option” CLI were treated with high doses of CD34 + cells. The absolute number of applied BM-MNCs correlated with the improvement of inflammation. We hypothesize that the therapeutic benefit of cell therapy for peripheral artery disease is the result of synergistic effects mediated by a mixture of active cells with regenerative potential. Patients at the most advanced stage of CLI do not appear to be suitable candidates for cell therapy. Trial registration The study was approved and registered by the ISRCTN registry. Trial registration: ISRCTN16096154 . Registered: 26 July 2016.