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.


Journal

Cardiovascular diabetology
ISSN: 1475-2840
Titre abrégé: Cardiovasc Diabetol
Pays: England
ID NLM: 101147637

Informations de publication

Date de publication:
28 09 2022
Historique:
received: 12 07 2022
accepted: 12 09 2022
entrez: 28 9 2022
pubmed: 29 9 2022
medline: 1 10 2022
Statut: epublish

Résumé

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. 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 50 patients were consecutively enrolled and the primary endpoint was 16%. TcPO 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.

Sections du résumé

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
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.

Identifiants

pubmed: 36171587
doi: 10.1186/s12933-022-01629-y
pii: 10.1186/s12933-022-01629-y
pmc: PMC9516816
doi:

Substances chimiques

Oxygen S88TT14065

Types de publication

Journal Article Observational Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

196

Informations de copyright

© 2022. The Author(s).

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Auteurs

Andrea Panunzi (A)

Diabetic Foot Dpt, IRCCS MultiMedica, Milan, Italy.

Fabiana Madotto (F)

Value-based Healthcare Unit, IRCCS MultiMedica, Milan, Italy.

Elena Sangalli (E)

Laboratory of Cardiovascular Pathophysiology-Regenerative Medicine, IRCCS MultiMedica, Milan, Italy.

Federica Riccio (F)

Laboratory of Cardiovascular Pathophysiology-Regenerative Medicine, IRCCS MultiMedica, Milan, Italy.

Adriana Barbara Sganzaroli (AB)

Diabetic Foot Dpt, IRCCS MultiMedica, Milan, Italy.

Paolo Galenda (P)

Diabetic Foot Dpt, IRCCS MultiMedica, Milan, Italy.

Amelia Bertulessi (A)

Diabetic Foot Dpt, IRCCS MultiMedica, Milan, Italy.

Maria Francesca Barmina (MF)

Diabetic Foot Dpt, IRCCS MultiMedica, Milan, Italy.

Ornella Ludovico (O)

Diabetic Foot Dpt, IRCCS MultiMedica, Milan, Italy.
Unit of Endocrinology, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy.

Orazio Fortunato (O)

Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Francesco Setacci (F)

Vascular Surgery Unit, IRCCS MultiMedica, Milan, Italy.

Flavio Airoldi (F)

Interventional Cardiology Unit, IRCCS MultiMedica, Milan, Italy.

Davide Tavano (D)

Interventional Cardiology Unit, IRCCS MultiMedica, Milan, Italy.

Laura Giurato (L)

Diabetic Foot Unit, University of Rome Tor Vergata, Rome, Italy.

Marco Meloni (M)

Diabetic Foot Unit, University of Rome Tor Vergata, Rome, Italy.

Luigi Uccioli (L)

CTO Andrea Alesini Hospital, Division of Endocrinology and Diabetes, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.

Antonino Bruno (A)

Laboratory of Immunology and General Pathology, Department of Biotechnologies and Life Sciences, University of Insubria, Varese, Italy.
Laboratory of Innate Immunity, Unit of Molecular Pathology, Biochemistry and Immunology, IRCCS MultiMedica, Milan, Italy.

Gaia Spinetti (G)

Laboratory of Cardiovascular Pathophysiology-Regenerative Medicine, IRCCS MultiMedica, Milan, Italy. gaia.spinetti@multimedica.it.

Carlo Maria Ferdinando Caravaggi (CMF)

Diabetic Foot Dpt, IRCCS MultiMedica, Milan, Italy. caravaggi@me.com.

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