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

Ilaria Zollino; Diana Campioni; Maria Grazia Sibilla; Mirko Tessari; Anna Maria Malagoni; Paolo Zamboni

doi:10.1016/j.jcyt.2018.10.012

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

Cytotherapy. 2019 Feb;21(2):200-211. doi: 10.1016/j.jcyt.2018.10.012. Epub 2018 Dec 22.

Authors

Ilaria Zollino¹, Diana Campioni², Maria Grazia Sibilla³, Mirko Tessari⁴, Anna Maria Malagoni³, Paolo Zamboni⁴

Affiliations

¹ Department of Morphology, Surgery and Experimental Medicine, Section of Translational of Medicine and Surgery, University of Ferrara, Ferrara, Italy. Electronic address: zlllri@unife.it.
² Center of Hemostasis & Thrombosis, Department of Biomedical and Surgical Science, Section of Medical Biochemistry, Molecular Biology & Genetics, University of Ferrara, Ferrara, Italy.
³ Sant'Anna University Hospital, Unit of Translational Surgery and Vascular Diseases Center, Ferrara, Italy.
⁴ Department of Morphology, Surgery and Experimental Medicine, Section of Translational of Medicine and Surgery, University of Ferrara, Ferrara, Italy; Sant'Anna University Hospital, Unit of Translational Surgery and Vascular Diseases Center, Ferrara, Italy.

PMID: 30583949
DOI: 10.1016/j.jcyt.2018.10.012

Abstract

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.

Keywords: mixed leg ulcers; non-expanded adipose derived cells; non-healing venous leg ulcers; wound healing.

Publication types

Clinical Trial, Phase II
Randomized Controlled Trial

MeSH terms

Adipose Tissue / cytology*
Aged
Aged, 80 and over
Centrifugation / methods
Chronic Disease
Cohort Studies
Female
Humans
Immunophenotyping
Male
Middle Aged
Stem Cell Transplantation / adverse effects*
Stem Cell Transplantation / methods*
Treatment Outcome
Varicose Ulcer / therapy*
Wound Healing