A phase II randomized clinical trial for the treatment of recalcitrant chronic leg ulcers using centrifuged adipose tissue containing progenitor cells

Background aims. Preclinical and observational reports indicate that adipose tissue (AT) is a safe and promising tool to treat non-healing venous leg ulcers (VLUs). Methods. From an initial cohort of 38 patients, 16 patients affected by non-healing VLUs were randomly allocated to the experimental arm (5 men and 3 women) and control arm (5 men and 3 women). In the experimental arm, wounds were treated by debridement, centrifuged adipose tissue (CAT), advanced dressings and compression. No experimental treatment (CAT) was administered to the control arm. We investigated the functional and the immunophenotypical features of the harvested CAT-derived stem cells. The primary outcome measures were healing time and safety of the cell treatment. Secondary outcomes were pain evaluated by numeric rating scale (NRS), complete wound healing at 24 weeks by Margolis Index and wound-healing process expressed in square centimeters per week. The various immunophenotypic and functional characteristics of CAT-derived stem cells were then correlated with the clinical outcomes. Results. No major adverse events were recorded. The healing time was significantly faster by applying CAT, 17.5 +/- 7.0 weeks versus 24.5 +/- 4.9 weeks recorded in the control arm (P < 0.036). NRS dropped after the first week to 2.7 +/- 2.0 in the experimental arm versus 6.6 +/- 3.0 in the control group (P < 0.01). The rate of healing at the 24th week was not significantly different between arms. Interestingly, we found a strong reverse correlation between the percent of CD34(+)/CD45(-) non-hematopoietic cells, respectively, with the healing time (r = -0.894, P < 0.041) and NRS (r = -0.934, P < 0.020). Conclusions. CAT is safe and may accelerate healing time in VLUs as well as reduce wound pain. The percentage of CD34(+)/CD45(-) cells in stromal vascular fraction (SVF) seems to be a predictive biomarker of successful CAT treatment in these patients.