Long-term outcomes of autologous cell therapy in patients with ischaemic diabetic foot ulcers and no-option chronic limb threatening ischaemia

Abstract

Aim

Patients with ischaemic diabetic foot ulcers (DFUs) and no-option chronic limb-threatening ischaemia (CLTI) are reported to have a high risk of major amputation and mortality. Peripheral blood mononuclear cell (PB-MNCs) therapy has emerged as a promising adjunctive strategy, but long-term data remain limited. The study aimed to evaluate the long-term outcomes of PB-MNC therapy in patients with DFUs and NO-CLTI.

Methods

This prospective, single-centre, observational, controlled study included patients with ischaemic DFUs and no-option CLTI enrolled between January 2017 and September 2023. No-option CLTI was defined by a technical failure of lower limb revascularization with the absence of any below-the-ankle vessel and/or indirect revascularization with TcPO₂ values < 30 mmHg in the wound angiosome area. Patients were divided into two groups: those receiving PB-MNCs therapy plus standard of care (SoC) and those treated only with SOC based on conventional guidelines. PB-MNCs were administered by intramuscular injections along the anatomical area of the wound-related artery (2 or 3 cycles, 21–42 days apart). At 24 months of follow-up, outcomes assessed were healing, major amputation, and mortality. In the PB-MNC group, hospital readmission for recurrent CLTI requiring repeat revascularization was also recorded.

Results

Overall, 78 patients were included: 48 in the PB-MNCs group and 30 in the conventional therapy group. The mean age was 73.7 years, 84.6% were male, and most had type 2 diabetes (92.3%). At the baseline assessment, 71.8% of DFUs were infected, 83.3% were > 5 cm², and 88.5% had gangrene. At 24 months, the PB-MNCs group showed a higher rate of healing (60.4 vs. 20%, p < 0.0001), lower rate of major amputation (12.5 vs. 26.7%, p = 0.0004), and mortality (27.1 vs. 46.7%, p = 0.0002) than the control group. CLTI recurrence requiring readmission occurred in 3/48 (6.2%) among patients in the PB-MNC group.

Conclusions

In patients with ischaemic DFUs and NO-CLTI, adjunctive PB-MNCs therapy was associated with better long-term outcomes in comparison to conventional therapy.