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

Overview

Journal Cardiovasc Diabetol

Publisher Biomed Central

Specialties Cardiology & Vascular Diseases
Endocrinology

Date 2022 Sep 28

PMID 36171587

Authors

Andrea Panunzi

Fabiana Madotto

Elena Sangalli

Federica Riccio

Adriana Barbara Sganzaroli

Paolo Galenda

Amelia Bertulessi

Maria Francesca Barmina

Ornella Ludovico

Orazio Fortunato

Francesco Setacci

Flavio Airoldi

Davide Tavano

Laura Giurato

Marco Meloni

Luigi Uccioli

Antonino Bruno

Gaia Spinetti

Carlo Maria Ferdinando Caravaggi

Affiliations

Soon will be listed here.

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 (TcPO)].

Results: 50 patients were consecutively enrolled and the primary endpoint was 16%. TcPO 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 TcPO (≥ 40 mmHg) after the last treatment showed a high frequency of small EVs at enrollment.

Conclusions: In no-option CLTI diabetic patients, PB-MNCs therapy led to an improvement in tissue perfusion, a high rate of healing, and back-to-walk. Coupling circulating cellular markers of angiogenesis could help in the identification of patients with a better clinical benefit over time.

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