Stem Cells Show Promise for Nonhealing Diabetic Foot Ulcers in Phase 1 Trial

Michael Carstens, MD

Results of a phase 1 study funded by the Diabetes Research Institute Foundation suggest stem cell therapy could be an effective treatment for nonhealing diabetic foot ulcers and possibly reduce the need for amputations in these patients.

The study, which used a cell preparation containing stem cells harvested from the patient’s own fat, was carried out in 63 patients with nonhealing ulcers considered to be amputation candidates and returned results indicating most patients achieved 100% healing at 12 months.

"The healing process was observed to take place indifferent directions: from the periphery, as expected, but also by upward proliferation from the ulcer bed," noted lead investigator Michael Carstens, MD, of Wake Forest University's Institute of Regenerative Medicine, in a statement. "In several cases, newly developed tissue was capable of covering previously exposed tendons. Furthermore, even among ulcers greater than 10 cm2 virtually all patients achieved 85 percent closure or better by 6 months.”

Building on previous research from trials led by Carstens and Diego Correa, MD, PhD, of the University of Miami, the pair sought to assess the safety and efficacy of local injections of autologous adipose-derived stromal vascular fraction (SVF) cells as a treatment for nonhealing diabetic foot ulcers. In total, 63 patients from Nicaragua were assessed for eligibility and included in the study, all of whom were considered candidates for amputation.

For inclusion in the study, patients need to have active type 2 diabetes requiring treatment, a nonhealing ischemic unclear of the lower extremity measuring 3 centimeters or more that has been present for longer than 3 months, and clinically approaching the need for amputation. Investigators noted exclusion criteria included being less than 30 years of age, presence of unstable cardiovascular disease at enrollment, presence of chronic pulmonary disease, presence of an ongoing infection and/or sepsis, and uncontrolled diabetes.

Patients included in the study were treated with 30x10 6 SVF cells injected into the margins and bed of the ulcer and the vascular territories of the tibialis anterioris, dorsalis pedis, and tibialis posterioris. Investigators noted SVF cells were obtained using the GID SVF-2 device after lipoaspiration.

The primary endpoint of the trial was the safety of the GID SVF-2 device processing and association SVF injection therapy. Safety endpoints included adverse effects as a result of the adipose tissue harvesting procedure, injection of SVF cells, and the therapy itself. Secondary outcomes of interest included the percentage of patients with wound closure at 6 and 12 months, which investigators defined as intact epithelial coverage without the need for further dressing changes.

At 6 months, investigates had lost 4 patients to follow-up, including 3 with previously scheduled amputations and 1 who died from cardiovascular causes. By 12 months, 9 patients had been lost to follow-up, leaving a cohort of 54 patients for the investigators’ final analysis. At 6 month evaluations, 51 of 59 patients had 100% diabetic foot ulcer closure and the remaining 8 had closure of 75% or more. At 12 months, 50 of 54 patients had 100% diabetic foot ulcer healing and the remaining 4 had 85% or greater healing.

While 5 patients died during the study, safety analyses indicated none of these deaths were intervention-related. Furthermore, no intervention-related serious adverse events were reported during the trial.

"Non-healing diabetic foot ulcers usually have no effective form of treatment," said Anthony Atala, MD, Editor-in-Chief of STEM CELLS Translational Medicine and Director of the Wake Forest Institute for Regenerative Medicine, in the aforementioned statement. "This work should be reviewed as it demonstrates the possibility of a novel cell injection therapy that can alleviate pain and infection, accelerate wound healing, and possibly avoid amputation."

This study, “Treatment of chronic diabetic foot ulcers with adipose-derived stromal vascular fraction cell injections: Safety and evidence of efficacy at 1 year,” was published in STEM CELLS Translational Medicine.