Results of a prospective observational study of autologous peripheral blood mononuclear cell therapy for no-option critical limb-threatening ischemia and severe diabetic foot ulcers

Abstract
Background: Cell therapy with autologous peripheral blood mononuclear cells (PB-MNCs) may help restore limb
perfusion in patients with diabetes mellitus and critical limb-threatening ischemia (CLTI) deemed not eligible for
revascularization procedures and consequently at risk for major amputation (no-option). Fundamental is to establish
its clinical value and to identify candidates with a greater benefit over time. Assessing the frequency of PB circulating
angiogenic cells and extracellular vesicles (EVs) may help in guiding candidate selection.
Methods: We conducted a prospective, non-controlled, observational study on no-option CLTI diabetic patients that
underwent intramuscular PB-MNCs therapy, which consisted of more cell treatments repeated a maximum of three
times. The primary endpoint was amputation rate at 1 year following the first treatment with PB-MNCs. We evaluated
ulcer healing, walking capability, and mortality during the follow-up period. We assessed angiogenic cells and EVs
at baseline and after each cell treatment, according to primary outcome and tissue perfusion at the last treatment
[measured as transcutaneous oxygen pressure (
TcPO2)].
Results: 50 patients were consecutively enrolled and the primary endpoint was 16%. TcPO2
increased after PB-MNCs
therapy (17.2 ± 11.6 vs 39.1 ± 21.8 mmHg, p < .0001), and ulcers healed with back-to-walk were observed in 60%
of the study population (88% of survivors) during follow-up (median 1.5 years). Patients with a high level of TcPO2
(≥ 40 mmHg) after the last treatment showed a high frequency of small EVs at enrollment.