Treatment of Chronic Diabetic Foot Ulcers with Adipose-Derived Stromal Vascular Fraction Cell Injections: Safety and Evidence of Efficacy at 1 Year

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 adiposederived 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%

Mesenchymal Stem Cells Overexpressing ACE2 Favorably Ameliorate LPS-Induced Inflammatory Injury in Mammary Epithelial Cells

“…The therapeutic potential of MSCs has been widely demonstrated in various diseases, including asthma ( 16), rheumatoid arthritis (17,18), and Crohn's disease (19,20). Numerous clinical trials and tests around the world have validated the ability of MSCs to alleviate inflammation (15,21,22). In this study, we demonstrated that MSC and MSC-GFP can reverse LPS-induced injury in EpH4-Ev cells.…”

Novel topical allogeneic bone-marrow-derived mesenchymal stem cell treatment of hard-to-heal diabetic foot ulcers: a proof of concept study

“…Although the treatment consisted of simultaneous systemic and local injection therapy combined with topical application [ 18 ]. Other studies have examined the safety of topically applied adipose tissue derived MSCs and did not report any AEs associated to the investigated treatment [ 28 , 29 ]. However, no studies have reported on safety or efficacy when treating DFUs with topical BM-MSCs alone.…”

Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells and Their Contribution to Angiogenic Processes in Tissue Regeneration

“…AT-MSCs and their secretome are described not only in in vitro studies, but also in many clinical trials. A recent publication by Carstens et al [ 94 ] demonstrated the safety and beneficial effect of an adipose stromal vascular fraction injection, containing both endothelial progenitor cells and MSCs, into the wound bed and periphery of patients with large diabetic foot ulcers (>3 cm in diameter). Over a one-year observation, significant wound healing was observed, leading to complete healing of the wound in the majority of cases.…”