Abstract
Diabetes affects multiple systems in complex manners. Diabetic foot ulcers (DFUs) are a result of diabetes-induced microarterial vessel disease and peripheral neuropathy. The presence of arteriosclerosis-induced macroarterial disease can further complicate DFU pathophysiology. Recent studies suggest that mesenchymal stromal cell therapies can enhance tissue regeneration. This phase I study was designed to determine the safety and explore the efficacy of local injections of autologous adipose-derived stromal vascular fraction (SVF) cells to treat nonhealing DFUs greater than 3 cm in diameter. Sixty-three patients with type 2 diabetes with chronic DFU-all amputation candidates-were treated with 30 × 10(6) SVF cells injected in the ulcer bed and periphery and along the pedal arteries. Patients were seen at 6 and 12 months to evaluate ulcer closure. Doppler ultrasounds were performed in a subset of subjects to determine vascular structural parameters. No intervention-related serious adverse events were reported. At 6 months, 51 subjects had 100% DFU closure, and 8 subjects had ≥75% closure. Three subjects had early amputations, and one subject died. At 12 months, 50 subjects had 100% DFU healing and 4 subjects had ≥85% healing. Five subjects died between the 6- and 12-month follow-up visits. No deaths were intervention related. Doppler studies in 11 subjects revealed increases in peak systolic velocity and pulsatility index in 33 of 33 arteries, consistent with enhanced distal arterial runoff. These results indicate that SVF can be safely used to treat chronic DFU, with evidence of efficacy (wound healing) and mechanisms of action that include vascular repair and/or angiogenesis.