Cardiovascular Diabetology (Sep 2022)

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

  • 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

DOI
https://doi.org/10.1186/s12933-022-01629-y
Journal volume & issue
Vol. 21, no. 1
pp. 1 – 10

Abstract

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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. 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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