Human umbilical cord mesenchymal stromal cells derivatives in treating diabetic foot ulcers: a phase I/II safety and efficacy trial

Abstract

Diabetic foot ulcers (DFUs) are serious and prevalent complications of diabetes mellitus, affecting up to 34% of individuals and contributing substantially to morbidity, healthcare expenditures, and the risk of non-traumatic lower limb amputations. Despite the availability of standard treatment protocols, achieving complete and sustained healing remains a significant clinical challenge. This study investigates the safety and efficacy of allogeneic human umbilical cord mesenchymal stromal cell derivatives (hUC-MSCD), including conditioned media, extracellular vesicles, and exosomes, administered via perilesional injection in patients with chronic DFUs. In this single-center, phase I/II, open-label clinical trial (NCT06825884), ten adult patients (7 males, 3 females; mean age: 52.2 years) with type 2 diabetes mellitus and chronic DFUs classified as Texas Grade II–III (mean ulcer duration: 15 weeks), refractory to standard care, were enrolled. Participants received perilesional injections of allogeneic hUC-MSCD. Safety was evaluated through the monitoring of adverse events, and efficacy was assessed by the rate and duration of ulcer closure, as well as recurrence during follow-up. The intervention was well tolerated, with no significant adverse events observed. All patients achieved complete ulcer closure within a mean of 4.2 weeks (p < 0.00001). Importantly, no ulcer recurrence was documented during a 24-month follow-up period. These results provide strong preliminary evidence that allogeneic hUC-MSCD therapy is both safe and effective in promoting wound healing in refractory DFUs. Larger, randomized, double-blind, placebo-controlled trials are warranted to validate these findings and to further define the therapeutic potential of hUC-MSCD in this population.