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

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