Effects of adipose-derived stem cells treatment in chronic leg ulcers. A phase II randomized clinical trial

Background: Adipose tissue is a source of different type of stem cells (ASCs). We investigated safety and effects of ASCs in a phase II rand-omized clinical trial, in the feld of recalcitrant venous leg ulcer (VLU). In addition we evaluated a reproducible methodological approach to standardize the isolation, characterization and the clinical use of the ASCs for ulcer wound healing. Finally, the biological data were corre-lated with the clinical follow-up of the patients after treatment. Methods: Sixteen (16) patients affected by chronic venous leg ulcers were randomized. ASCs were harvested using Coleman's technique and inject-ed into the ulcers. We assessed also: healing time, post-treatment pain with numerical scale (NRS), Margolis Index (MI), and patients healed into 28 weeks. In laboratory a sample of the same cells was processed in order to characterize the amount and the type of stem cell. The in vitro clonogenic output was evaluated as colony forming unit fibroblasts (CFU-F). Results: The patients treated with ASCs heal in a minor time, 17.5±7.0 weeks vs. 24.5±4.9 (P<0.036). The clinical course was less painful in ASCs arm 2.7±2.0 vs. 6.6±3.0 (P<0.01). The MI was positive in 50% of patients vs. 25% of controls (P<0.3). High number of CD34+/CD45-stem cells was observed (mean of 82.6±16) and supra adventitial component and pericytes are the most represented. Laboratory results also show a linear correlation between MI respectively with the number of CFU-F (r=0.94), the number of pericytes (P=0.98). Conclusions: The experimented procedure demonstrated to be safe as well as, by using the standard methods herein assessed in the lab, also signifcant clinical benefts. This study encourages to plan a wider phase III trial.